Blood transfusion

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BLOOD TRANSFUSION

OXFORD MEDICAL PUBLICATIONS

BLOOD TRANSFUSION

GEOFFREY KEYNES

M.A., M.D. CANTAB., F.B.C.S. ENG.
SECOND ASSISTANT, SITRGICAL PROFESSORIAL UNIT

ST. Bartholomew's hospital

LONDON

HENRY FROWDE and HODDER & STOUGHTON

THE LANCET BUILDING

1 BEDFORD STREET, STRAND, W.C.2

First published m 1922

PRINTED IN GREAT BRITAIN

BZ HAZELL, WATSON AND VINEY, LD.

LONDON AND AYLESBXJRY.

PREFACE

Blood transfusion is of rapidly growing importance in
modern therapeutics, yet the subject has only been repre-
sented in the medical literature of this country hitherto
by isolated communications concerning special points.
The present work seeks to give a connected account of the
whole subject and of the problems arising from it, together
with practical instructions for performing transfusions
by an efficient and simple method.

I am indebted for helpful criticisms and suggestions to
Professor A. V. Hill, F.R.S., of Manchester University.
Dr. J. H. Drysdale has kindly allowed me to use the
records of three cases of pernicious anaemia treated in his
wards at St. Bartholomew's Hospital. Dr. Joekes has per-
mitted me to refer to some of his own observations con-
cerning abnormal serum reactions. Dr. R. M. Janes has
given me some account of the important work recently
done by Dr. Bruce Robertson and himself at the Hospital
for Sick Children, Toronto.

The Bibliography at the end of the book makes no pre-
tence of being absolutely complete. It is, however, more
extensive than any that has yet been printed, and I believe
that it contains references to nearly all the contributions of
present importance published up to the date of going to
press. Numbers referring to the Bibliography have been
inserted in the text only where no name is given to the
authority quoted.

' Geoffrey Keynes.

86, Harley Street, W.l.
February 1922.

CONTENTS

CHAPTER I

PAGB

Historical Sketch ...... 1

CHAPTER II

Indications for Blood Transfusion : HiEMOR-

RHAGE AND ShOCK ..... 19

CHAPTER III

Indications for Blood Transfusion — continued :
Hemorrhagic Diseases — Blood Diseases —
Toxemias ....... 44

CHAPTER IV
Dangers of Blood Transfusion ... 67

CHAPTER V

Physiology and Pathology of Blood Groups . 79

CHAPTER VI

The Choice of Blood Donor .... 97

CHAPTER VII

The Methods of Blood Transfusion . .108

Bibliography . 137

Index . . . . . . . . . 159

BLOOD TRANSFUSION

CHAPTER I

HISTORICAL SKETCH

From the earliest times the vital importance of blood to
the human system has been fully appreciated. It has been
supposed to carry in it some of the virtues, such as the
youth and health, of its possessor, and it has therefore been
commonly regarded as a sacrifice acceptable to the gods.
References to blood in the Old Testament, in classical
authors, and, it is stated, in the writings of the ancient
Egyptians, refer rather to these mystical attributes than
to any definite transference of it from the veins of one
animal to those of another. One of the earliest references
to actual transfusion of blood that has been noticed is to
be found in a work by Libavius of Halle, published in 1615.
The passage has been translated as follows :

'' Let there be present a robust healthy youth full of
lively blood. Let there come one exhausted in strength,
weak, enervated, scarcely breathing. Let the master of
the art have little tubes that can be adapted one to the
other ; then let him open an artery of the healthy one,
insert the tube and secure it. Next let him incise the
artery of the patient and put into it the feminine tube.
Now let him adapt the two tubes to each other and the
arterial blood of the healthy one, warm and full of spirit,
will leap into the sick one, and immediately will bring him
to the fountain of life, and will drive away all languor."

It may be assumed, however, that this was only an idea,
and had not yet been carried into practice. It was, indeed,
unlikely that any attempt to perform blood transfusion
1

2 BLOOD TRANSFUSION

would be made until the conception of the circulation of
the blood had been promulgated, and this in 1615 had not
yet taken place.

William Harvey had been appointed physician to St.
Bartholomew's Hospital in 1609, and already in 1616 as
Lumleian lecturer had stated his theory of the circulation,
but not until its publication twelve years later could it be
generally known. His treatise entitled Eocercitatio Anato-
mica de Motu Cordis et Sanguinis in Animalibus, which
appeared in 1628, may therefore be regarded as the point
from which blood transfusion first arose. 'It has often
been stated in the literature of the subject that the first
transfusion was performed in 1492, when the blood of
three boys is supposed to have been transfused into the
veins of the aged Pope Innocent VIII. ^ This, however,
seems to have been a mis-statement of the facts. Actually
a Jewish physician prepared a draught for the Pope from
the blood of three boys, who were bled to death for the
purpose. 2 The drinking of blood was not a new idea; this
particular incident is of no special interest, and may now
be allowed to sink into oblivion.

It is not until after the middle of the seventeenth century
that authentic references to blood transfusion are to be
found. The first is in the writings of Francesco Folli, a
Florentine physician, who claims to have demonstrated
the operation of transfusion of blood on August 13, 1654,
to the Grand Duke Frederick II. There does not seem to
be any confirmation of this in the writings of others. A
few years later experimental work tending in the same
direction was being done in England, and the inception of
this was due to the ingenious Sir Christopher Wren, who
in this connexion has not hitherto received the recognition
that is his due. Dr. Wren, as he was designated at the
time, was one of the most active members of the recently

1 The first reference to this that I can find is in " Moines et Papes," by
Emile Gebhardt, La Chronique Medicale, November 1912.

2 Life and Times of Rodrigo Borgia, A. H. Mathew, D.D., 1912, p. 66.

HISTORICAL SKETCH 8

formed Royal Society, and was responsible for many new
experiments in several sciences. It is clear from references
in the Philosophical Transactions that his first experiments
were done in 1659, and the following statement is made by
Dr. Thomas Sprat in his History of the Royal Society,
published in 1667 :

" He was the first author of the Noble Anatomical
Experiment of Injecting Liquors into the Veins of Animals.
An Experiment now vulgarly known ; but long since
exhibited to the Meetings at Oxford, and thence carried
by some Germans, and published abroad. By this Opera-
tion divers Creatures were immediately purg'd, vomited,
intoxicated, kill'd, or reviv'd according to the quality of
the Liquor injected : Hence arose many new Experiments,
and chiefly that of Transfusing Blood, which the Society
has prosecuted in sundry Instances, that will probably end
in extraordinary Success " (p. 317).

Sir Christopher Wren did not actually carry out any
transfusion experiments on his own account. This was
done by his friend, Richard Lower, well known for his
work on the anatomy of the heart, who worked in the
laboratory of Thomas Willis at Oxford. In these experi-
ments, some account of which was published in 1666, he
used a silver cannula for obtaining continuity between the
artery of one animal and the vein of another. Lower must
therefore receive the credit for having done the first trans-
fusion actually performed in England. In the following
year other experiments were done by Dr. Edmund King
and Thomas Cox, both of whom recorded their experiences
in the Philosophical Transactions.

Meanwhile Wren's work had become known in other
countries, and it is said that transfusion was performed in
1664 by Daniel of Leipsic, who thus anticipated the work
of Lower. However this may be, the first transfusion done
upon a human being was certainly carried out in France by
Jean Denys of Montpellier, physician to Louis XIV. This
is admitted in the Philosophical Transactions, but the

4 BLOOD TRANSFUSION

following statement in extenuation of English hesitancy is
made :

" We readily grant, They were the first, we know off,
that actually thus improved the Experiment ; but then
they must give us leave to inform them of this Truth, that
the Philosophers in England had practised it long agoe upon
Man, if they had not been so tender in hazarding the Life
of Man (which they take so much pains for to preserve and
relieve), nor so scrupulous to incurre the Penalties of the
Law, which in England, is more strict and nice in case of
this concernment, than those of many other Nations are."

Dr. Edmund King further asserts that " We have been
ready for this Experiment these six Months," that is to say,
since March, 1667. Moral precedence must, however, give
way to the actual, and it is clear that Denys had snatched
the laurels. A translation of a full and interesting account
of his earlier experiment upon animals and his first two
transfusions done upon men was published in the Philoso-
phical Transactions for July 22, 1667. Of the first of these
he wrote as follows :

" On the 15 of this Moneth, we hapned upon a Youth
aged between 15 and 16 years, who had for above two
moneths bin tormented with a contumacious and violent
fever, which obliged his Physitians to bleed him 20 times,
in order to asswage the excessive heat.

" Before this disease, he was not observed to be of a
lumpish dull spirit, his memory was happy enough, and he
seem'd chearful and nimble enough in body ; but since
the violence of his fever, his wdt seem'd wholly sunk, his
memory perfectly lost, and his body so heavy and drowsie
that he was not fit for any thing. I beheld him fall asleep
as he sate at dinner, as he was eating his Breakfast, and in
all occurrences where men seem most unlikely to sleep.
If he went to bed at nine of the clock in the Evening, he
needed to be wakened several times before he could be got
to rise by nine the next morning, and pass'd the rest of the
day in an incredible stupidity.

I

HISTORICAL SKETCH 5

' I attributed all these changes to the great evacuations

of blood, the Physitians had been oblig'd to make for

saving his life, and I perswaded myself that the little they

had left him was extreamly incrustated [? incrassated] by

the ardour of the fever. . . . Accordingly my conjecture

was confirmed by our opening one of his Veins, for we

beheld a blood so black and thick issue forth, that it could

hardly form itself into a thread to fall into the porringer.

We took about three ounces at five of the Clock in the

morning, and at the same time we brought a Lamb, whose

Carotis Artery we had prepar'd, out of which we immitted

into the young man's Vein, about three times as much of

its Arterial blood as he had emitted into the Dish, and then

having stopt the orifice of the Vein with a little bolster, as

is usual in other phlebotomies, we caus'd him to lie down on

his Bed, expecting the event ; and as I askt him now and

then how he found himself, he told me that during the

operation he had felt a very great heat along his Arm, and

since perceiv'd himself much eased of a pain in his side,

which he had gotten the evening before by falling down a

pair of staires of ten steps ; about ten of the clock he was

minded to rise, and being I observed him cheerful enough,

I did not oppose it ; and for the rest of the day, he spent it

with much more liveliness than ordinary ; eat his Meals

very well, and shewed a clear and smiling countenance.

. . . He grows fat visibly, and in brief, is a subject of

amazement to all those that know him, and dwell with

him."

This boy had been transfused for therapeutic purposes ;
the second transfusion performed by Denys was done
upon an older man " having no considerable indisposition,"
and was purely experimental. About twenty ounces of
lamb's blood are stated to have been transfused, but the
procedure was without any ill effect, and it may be
doubted whether the man received as much as this.
^ In the succeeding number of the Philosophical Trans-
actions, October 21, 1667, the remarks of another French

6 BLOOD TRANSFUSION

experimenter, Gaspar de Gurye, are quoted. These are of
considerable interest, as they contain the first warning of
the dangers attending the administration of incompatible
blood. De Gurye affirms " that an expert Acquaintance
of his, transfusing a great quantity of blood into several
Doggs, observed alwayes, that the Receiving Doggs pissed
Blood." ^.-^^^

Other cases were subsequently recorded by Denys. In
one he claims to have cured a patient suffering from " an
inveterate Phrenzy." His account of it is too long to be
quoted here in full, but it is of special interest in that it
contains the first account of haemolysis and the attendant
symptoms in man which follow the transfusion of incom-
patible blood. The blood of a calf was used in this instance
and on two occasions ; at the first transfusion only a small
amount was given, but at the second,

" the Patient must have received more than one whole
pound. As this second Transfusion was larger, so were
the effects of it quicker and more considerable. As soon
as the blood began to enter into his veins, he felt the like
heal along his Arm and under his Arm-pits which he had
felt before. His pulse rose presently, and soon after we
observed a plentiful sweat all over his face. His pulse
varied extremely at this instant, and he complained of
great pain in his Kidneys, and that he was not well in his
stomack, and that he was ready to choak unless they gave
him his liberty.

'' Presently the Pipe was taken out that conveyed the
blood into his veins, and whilst we were closing the wound,
he vomited store of Bacon and Fat he had eaten half an
hour before. He found himself urged to Urine, and asked
to go to stooll. He was soon made to lie down, and after
two good hours strainings to void divers liquors, which
disturbed his stomack, he fell asleep about 10 a Clock, and
slept all that night without awakening till next morning,
was Thursday, about 8 a Clock. When he awakened, he
shewed a surprising calmness, and a great presence of

HISTORICAL SKETCH 7

mind, in expressing all the pains and a general lassitude he
felt in all his limbs. He made a great glass full of Urine,
of a colour as black, as if it had been mixed with the soot of
Chimneys."

The hsemoglobinuria, which was not at that time
attributed to its true cause, cleared up in the course
of a few days, and the patient appeared to be greatly
benefited.

Although the first transfusion performed upon a human
being was done in France, similar experiments were shortly
afterwards carried out in England. The passage already
quoted concerning the " sundry instances " mentioned in
Sprat's History of the Royal Society is amplified by the
diarist, Samuel Pepys, who witnessed the experiments on
at least one occasion. His first reference to the subject is
under the date November 14, 1666 :

" Here [at the Pope's Head] Dr. Croone told me, that, at
the meeting at Gresham College to-night, . . . there was
a pretty experiment of the blood of one dogg let out, till
he died, into the body of another on one side, while all his
own run out on the other side. The first died upon the
place, and the other very well, and likely to do well. This
did give occasion to many pretty wishes, as of the blood
of a Quaker to be let into an Archbishop, and such like ;
but, as Dr. Croone says, may, if it takes, be of mighty use
to man's health, for the amending of bad blood by borrow-
ing from a better body." {Diary, ed. Wheatley, vi. p. 60.)

Two days later he reports :

" This noon I met with Mr. Hooke, and he tells me the
dog which was filled with another dog's blood, at the College
the other day, is very well, and like to be so as ever, and
doubts not its being found of great use to men, — and so do
Dr. Whistler, who dined with us at the tavern." (Ibid.,
p. 63.)

On November 28 there was further conversation at
Gresham College to the same effect (ibid., p. 79). In the
following year the experiments were taken a stage further,

8 BLOOD TRANSFUSION

and Pepys refers again to them under the date November
21, 1667 :

" Among the rest they discourse of a man that is a Httle
frantic, that hath been a kind of minister. Dr. Wilkins
saying that he hath read for him in his church, that is poor
and a debauched man, that the College have hired for 20^.
to have some of the blood of a sheep let into his body ; and
it is to be done on Saturday next. They purpose to let in
about twelve ounces ; which they compute, is what will
be let in in a minute's time by a watch. They differ in the
opinion they have of the effects of it ; some think it may
have a good effect upon him as a frantic man by cooling
his blood, others that it will not have any effect at all.
But the man is a healthy man, and by this means will be
able to give an account what alteration, if any, he do find
in himself, and so may be usefull." (Diary, vii. p. 195.)

On November 29 Pepys. dined at a house of entertain-
ment, and enjoyed good company.

" But here, above all, I was pleased to see the person
who had his blood taken out. He speaks well, and did
this day give the Society a relation thereof in Latin, saying
that he finds himself much better since, and as a new man,
but he is cracked a little in his head, though he speaks very
reasonably, and very well. He had but 205. for his suffer-
ing it, and is to have the same again tried upon him : the
first sound man that ever had it tried on him in England,
and but one that we hear of in France, which was a porter
hired by the virtuosos." ^ (Ibid:, p. 205.)

The subject of this experiment was Arthur Coga, an
indigent Bachelor of Divinity of Cambridge, aged about
thirty-two. It is recorded in the Philosophical Trans-
actions that the experiment was performed by Richard
Lower and Edmund King at Arundel House on November
23, 1667, in the presence of many spectators, including
several physicians. Coga, when asked why he had not the
blood of some other creature transfused into him, rather

1 This refers to the experiment of Denys, mentioned above.

HISTORICAL SKETCPI

p

H| than that of a sheep, rephed : " Sanguis ovis symbolicam
quandam facultatem habet cum sanguine Christi, quia
Christus est agnus Dei." ^ It was estimated that Coga
received eight or nine ounces of blood, but he seems to
have felt no effects, good or ill, and it is probable that he
did not actually receive as much as this.

These beginnings in England and France led to the more
frequent use of blood transfusion, but soon afterwards the
operation fell into disrepute. Disasters followed the
transfusions, and the practice also met with violent opposi-
tion on the ground that terrible results, such as the growth
of horns, would follow the transfusion of an animal's blood
into a human being. In consequence of this they were
actually forbidden in France by the Supreme Court until
the Faculte of Paris should signify its approval, but the
necessary permission was not given. The " extraordinary
success " predicted by Sprat and the sanguine expectations
of Pepys and his friends were destined not to be fulfilled
until a later age.

For more than a hundred years the possibilities of blood
transfusion were almost entirely neglected. There are
some isolated references to it in medical writings towards
the end of the eighteenth century, but of these it is only
necessary to notice two. In 1792, at Eye in Suffolk, blood
from two lambs was transfused by a Dr. Russell into a boy
suffering from hydrophobia, and he claimed that the
patient's recovery was to be attributed to the treatment.
Soon afterwards in 1796 Erasmus Darwin recommended
transfusion for putrid fever, cancer of the oesophagus, and
in other cases of impaired nutrition. He suggested that
the blood should be transferred from donor to recipient
through goose quills connected by a short length of
chicken's gut, which could be alternately allowed to fill
from the donor and emptied by pressure into the patient.
This operation he never actually performed.

A more general interest in the subject was revived in

1 Birch's History oj the Royal Society, 175G, ii. p, 216,

10

BLOOD TRANSFUSION

England by the work of James Blundell, lecturer on physio-
logy and midwifery at St. Thomas's and Guy's Hospitals.
He published in 1818 his earliest paper on experimental

Fig. 1. — Blundell' s Impellor

From Researches Physiological and Pathological, 1824

transfusion with a special form of syringe invented by
himself. His first apparatus consisted of a funnel-shaped
receptacle for the blood, connected by a two-way tap with
a syringe from which the blood was injected through a tube
and cannula into the recipient. His experiments were

HISTORICAL SKETCH 11

r

^P performed upon dogs, and he began by drawing blood from
the femoral artery and re-injecting it into the same animal
through the femoral vein. He then conducted a long series
of investigations into the properties of blood, the effects
of its withdrawal, and the resuscitation of an exsanguinated
animal. Soon he had opportunities of transfusing patients
withjiumaa-blood, and the results are recorded in his

paper of lg24. His apparatus had by then been elaborated,

and an engraving of his Impellor, as he termed it, is repro-
duced here. It consisted as before of a funnel-shaped
\^m receptacle for the blood, but the syringe was now in-
^B corporated in one side of the funnel, and contained a
^B complicated system of spring valves, which caused the blood
^B to travel along the delivery tube when the piston was
^H pushed down. The Impellor was fixed to the back of a
^B chair in order to give it stability.

^B All the patients transfused by Blundell were either
^B exceedingly ill, or, judging from his description, already
^^ dead, so that his results, considered statistically, were not
favourable ! Nevertheless, he was not discouraged, and
stated his " own persuasion to be that transfusion by the
syringe is a very feasible and useful operation, and that,
after undergoing the usual ordeal of neglect, opposition,
and ridicule, it will, hereafter, be admitted into general
practice. Whether mankind are to receive the first benefit
of it, in this or any future age, from British surgery, or that
of foreign countries, time, the discoverer of truth and false-
hood, must determine." Blundell's work has been de-
scribed in some detail because, after the experimental work
of the seventeenth century, the year 1818 may be taken to
mark the real beginning of the clinical application of blood
transfusion.

The chief difficulty in the way of successful transfusion
was, of course, the obstacle introduced by the coagulation
of the blood. Bischoff in 1835 sought to overcome this
by injecting defibrinated blood, and that solution of the
difficulty was adopted by many operators, including Sir

12 BLOOD TRANSFUSION

Thomas Smith, who, in 1873, used defibrinated blood for
transfusing a case of melsena neonatorum at St. Bartholo-
mew's Hospital. The apparatus on this occasion consisted
of " a wire egg-beater, a hair sieve, a three-ounce glass
aspirator syringe, a fine blunt-ended aspirator cannula, a
short piece of india-rubber tubing with a brass nozzle at
either end connecting the syringe with the cannula, a tall
narrow vessel standing in warm water for defibrinating the
blood, and a suitable vessel floated in warm water to
contain the defibrinated blood." Others, too numerous to
be individually named, used the same method throughout
the nineteenth century and during the first ten years of
the twentieth. Even in 1914 a method of using defibrin-
ated blood was described by Moss. An objection was
raised in 1877 that it was dangerous to do this, owing to
the excess of fibrin ferment introduced with blood thus
treated, but this did not greatly discourage its use. Then,
as now, one of the chief uses of blood transfusion was found
to be in the practice of obstetrics. A series of 57 cases of
this kind were reported by Martin of Berlin in 1859, 43 of
these having been successful. A further series of cases was
collected by Blasius in 1863. He was able to report that
of 116 transfusions performed during the previous forty
years, in 56 the results were satisfactory. These statistics
did not indicate a remarkable degree of success. FataUties
due to the transfusion had occurred, attended by the
symptoms which we have now learned to associate with
incompatibility of the transfused blood. At that time,
however, the deaths were believed to be due chiefly to the
introduction of air bubbles into the circulation, although
it had been shown experimentally by Blundell in 1818, and
again by Ore in 1868, that small quantities, such as might
be accidentally introduced during a transfusion, produced
no ill effects. Some explanation, however, was required,
and so air bubbles for a long time received the blame.

Although some of the early experiments on blood trans-
fusion had been done in England, and although its revival

Fig. 2. — Mr. Higginson's Transfusion Instrument

A is a metallic cup, of 6-oz. capacity, to receive the supply of blood . B an outer casing, which
will hold 5 oz. of hot water, introduced through an aperture at C. D is a passage leading into an
elastic barrel, composed of vulcanized india-rubber, E, of which the capacity is 1 oz. F' the exit
for the blood into the injection-pipe G. At D and F there are ball-valves, capable of closing the
upper openings when thrown up against them, but leaving the lower openings always free. The
blood, or other fluid, poured into the cup A, has free power to run unobstructed through D, E, P ;
a small plug H is therefore provided to close the lower aperture F when necessary. The tube G-
is of vulcanized india-rubber, and terminates in a metal tube 0 for insertion into the vein. This
diagram is one-half the actual size of the instrument.

13

14 BLOOD TRANSFUSION

in the nineteenth century was initiated in England, yet it
is to be noticed that most of the references to it up to 1874
are to be found in the works of Continental writers. Never-
theless, an important modification was introduced into the
technique of the operation in 1857 by Higginson, who
applied the principle of a rubber syringe with ball-valves
for transferring the blood from the receptacle into which
it was drawn, to the vein of the recipient. This apparatus
is illustrated here, as it is of some interest in the history
of medicine. Higginson's syringe is now used for a
different purpose, but it was successfully applied by its
inventor in a series of seven cases which he duly reported.
One patient whom he transfused was suffering from
extreme weakness, which was attributed to the too pro-
tracted suckling of twins. He gave her about twelve
ounces of blood from a healthy female servant, and a state
of quietude followed her previous restlessness. A few
minutes later the patient was seized with a rather severe
rigor. It did not last long, but led to a state of reaction
and excitement, in which she sang a hymn in a loud voice.
The final result was good, and Higginson reports that in
five of the seven cases some benefit was to be attributed to
the transfusions. Later the same principle was used in
America by Aveling and by Fryer about the year 1874,
and subsequently it was in that country that nearly all
the important advances in the science of blood transfusion
were made.

In 1873 an inquiry was carried out by the Obstetrical
Society of London into the merits of transfusion, the
subject having been brought to the Society's notice by a
report of a case by Aveling, and an interesting summary of
the evidence was prepared by Madge in 1874. The results
do not seem to have been very encouraging, ''and transfusion
was still regarded as a procedure that was only to be used
as a last resource. Even at this date the bloodi'of other
animals was being used for transfusion, although the
practice had been discredited by Panum in 1863 and by

HISTORICAL SKETCH 15

others, and a series of eases was reported by Hasse in 1873,
in which lamb's blood was given for various conditions.
Other cases were reported from Italy (3) and Russia (101).
Sentiment, if not science, seems to have suggested that
there was something repulsive in bringing a lamb into the
sick chamber and mixing animal with human blood, but it
was remarked in a discussion on the subject that " it was
only taking lamb in another form."

After 1875, however, there was a decline in the amount of
attention given to transfusion which lasted for thirty
years. This was probably due in part to the increasing
number of fatalities which had followed the more general
use of transfusion, but, as Peterson suggests, it was also to
be accounted for by the increasing use of normal saline
solution for intravenous injection in the treatment of
haemorrhage. There was also a period during which the use
of milk was advocated for intravenous therapy (37, 279).
Soon after the beginning of the twentieth century trans-
fusion received a fresh impetus which has steadily gained
force up to the present time. The free use of cannulse
and syringes had always been hampered by the coagulation
of the blood, and it was clearly a great advance to be able
to perform a direct transfusion without the intervention of
any tube. This was made possible by great improvements
in the surgery of the blood-vessels, which were due in the
first place to the work of Murphy, published in 1897 ; they
were carried still further by others, such as Carrel and
Guthrie, and culminated in the work of Crile, who in 1907
put the technique of direct transfusion on a securer basis
than it had ever been before. His method is briefly
described in a later chapter of the present work. Mean-
while the chief factor responsible for previous fatalities
was being eliminated. The presence of agglutinins and iso-
agglutinins in the blood had been detected by Landsteiner
and by Shattock in 1901 ; in 1907 the four blood groups
into which human beings can be classified were determined
by Jansky and the work was repeated by Moss in 1910,

16 BLOOD TRANSFUSION

Simplification of the group tests soon followed, as is
described in another chapter. At the same time great im-
provements were made in the use of syringes, paraffined
tubes, and in anastomosis of the blood-vessels. In this
connexion one of the most notable contributions was made
by Curtis and David, who in 1911 introduced the use of
syringe transfusion through a two- armed tube coated on
the inside with paraffin. In 1913 indirect transfusion by
' means of the paraffined vessel was introduced by Kimpton
and Brown, and it was now evident that blood transfusion
was shortly to become a method of treatment which would
be without any very difficult technique, and could therefore
be more extensively applied.

The final advance was made in 1914, when the use of
sodium citrate as an anticoagulant was made possible by
the work of Lewisohn in America, of Hustin in Belgium,
and of several others, who all arrived independently, but
almost simultaneously, at the same conclusion. The use
of an anticoagulant was no new idea. In 1858 the use of
small quantities of ammonia had been suggested by B. W.
Richardson in the Guy's Hospital Reports, and in 1869
sodium phosphate was used in four obstetrical cases by
Braxton Hicks, who found that the process was greatly
facilitated thereby ; but neither of these methods came
into general use. It had long been known that hirudin or
leech extract, and the salts of oxalic acid or of citric acid,
could be used as anticoagulants outside the body, but
their supposed toxicity had prevented their being used for
transfusion. The proof that sodium citrate was both
efficient for this purpose and non-toxic in a dilution that
was still effective at once raised blood transfusion to a wider
sphere of usefulness than had been possible before. The
first transfusion of citrated blood was performed by
Professor L. Agote of Buenos Aires, on November 14, 1914,
a date which is therefore of the greatest importance in the
history of blood transfusion. A method had at last been
discovered which approached the ideal, since it united the

I

HISTORICAL SKETCH 17

four cardinal virtues of simplicity, certainty, safety, and
efficiency.

This great stride forward in the technique of blood
transfusion coincided so nearly with the beginning of the
war that it seemed almost as if foreknowledge of the
necessity for it in treating war wounds had stimulated
research. Yet during the first two years of the war almost
nothing was known in the British Army of its possibilities. I
I have no evidence that the French or German army doctors
were any better informed than ourselves. Some attempt
was made in 1916 to introduce the use of direct transfusion
through cannulae, but the technique was too difficult and
uncertain for the stress of war conditions. It was not until /
1917, when the British Army Medical Corps was being/
steadily reinforced with officers from the United States of
America, that knowledge of blood transfusion began to be
spread through the Armies. A conspicuous part was '
borne by Oswald Robertson in introducing the use of the
citrate method, and to him a very large number of men,
indirectly owe their lives. In some armies the paraffined)
vessel of Kimpton and Brown remained the favourite
method, but to me the citrate method seemed the more
suitable, because of the certainty with which success could
be attained, and the same view was taken by many others.
At the same time the investigators appointed by the
Medical Research Committee attempted to elucidate the
problems connected with haemorrhage and wound shock,
and their results, as will be seen, served to confirm the
estimate already being formed of the value of blood trans-
fusion.

In this way a large number of operators in this country
became familiar with the various methods, and transfusion
has in consequence been used increasingly in civilian
practice since the war. It is undoubtedly destined to
figure still more largely in the therapeutics of the future.
Meanwhile the public mind is becoming gradually more
used to the idea, and the time is past when every transfusion
2

18 BLOOD TRANSFUSION

is deemed worthy of a sensational headline in a newspaper.
Nevertheless, at the end of the year 1920 the following
advertisement appeared in the personal columns of The
Times :

" Will any Doctor who knows method of treating
cancer by transfusion of child's blood kindly write
Box — ."

So the wheel is come full circle, and the shade of Pope
Innocent VIII may well chuckle as he notes the small
advance in popular knowledge since the fifteenth century.

CHAPTER II

INDICATIONS FOR BLOOD TRANSFUSION

The indications for blood transfusion are gradually becom-
ing more numerous as experience of its effects accumulates,
and there can be no doubt that the value of transfusion as
a therapeutic measure is destined to become much more
generally recognized than it is at the present time. Lack
of knowledge, together with an exaggerated idea of the
difficulties of the process, is the chief obstacle to its more
extended use. Time and the education of the rising genera-
tion will provide the remedy for this.

The conditions for which blood transfusion may be used
fall into four well-defined groups. On the one hand are
those characterized by an acute anaemia, which demand the
performance of a blood transfusion as an emergency or
life-saving operation ; on the other hand are those in which
the anaemia is of slow onset, and is to be combated by a
single transfusion to tide the patient over an operation or
a critical period or by repeated transfusions in the hope of
prolonging the patient's life if not of obtaining a cure.
A third group includes the haemorrhagic diseases in which
the transfusion is administered not only to replace blood
which has been lost, but also to bring about cessation of
the haemorrhage. A fourth group includes cases of general
toxaemia, whether chemical or bacterial, in which the new
blood is given partly on account of its therapeutic pro-
perties, partly in order to dilute the circulating toxins or to
supply healthy red blood cells to carry on the oxygenation
of the tissues.

For the first and third of these groups blood transfusion

19

20 BLOOD TRANSFUSION

is now very firmly established as a method of treatment
which is of extraordinary value. For the second group it
may be regarded as a palliative to be given with circum-
spection. For the fourth group administration of blood is
still in the experimental stage.

In the present work each condition will be taken in
turn and, as far as possible, separately, though at the outset
it has been found undesirable to dissociate the two con-
ditions, haemorrhage and shock. The present position of
blood transfusion in relation to each condition will be
discussed ; its limitations and the precautions to be
observed will be described.

HAEMORRHAGE AND ShOCK

Blood transfusion is pre-eminently the best form of
treatment that is known for the condition of acute anaemia
following haemorrhage to whatever cause it may be due.
Its good efiects were seen by a number of operators in
many hundreds of exsanguinated patients during the latter
part of the war, and its value was then established upon a
secure foundation. It was unusual during the war to meet
with patients who were in danger of their lives from loss of
blood alone without the additional factor of traumatic
shock, but such cases did occur, and they are also to be met
I with in civil practice, as, for instance, in attempted suicide
' by throat cutting, in gastric ulcer with severe haematemesis,
and in secondary haemorrhage after operation. The more
typical condition following war wounds, haemorrhage with
I shock, will be faithfully reproduced in the victims of train
or street accidents, in patients who have undergone certain
severe operations, and in women suffering from post-partum
haemorrhage or a ruptured ectopic gestation.

The signs and symptoms of acute anaemia will be familiar
to most readers. It is characterized by a peculiar greyness
of the skin, by extreme pallor of the mucous membranes,
by a cold perspiration, by a thready and rapid pulse which

HEMORRHAGE AND SHOCK 21

may exceed 140 beats to the minute, and by extreme rest-
lessness. The " amaurosis " of the text-books is seldom
met with, but in the last stages the patient becomes semi-
unconscious, the restlessness tends to disappear, the
muscles relax, and the respiration takes on a peculiar sigh-
ing character, which is described as " air hunger," and
probably indicates exhaustion of the respiratory centre.
Meanwhile, if instruments are at hand, additional signs may
be recognized. The most important of these is a fall in
blood pressure. It has been stated that a systolic pressure
below 70 mm. of mercury is scarcely compatible with life,
but this is not in accordance with experience. It was
common during the war to meet with blood pressures
below 45 mm., so low in fact that they could not be
measured with the ordinary apparatus that was available,
but many patients whose lives had reached even so low an
ebb as this were quickly restored by the administration of
blood, provided that the exsanguinated state had not lasted
for too long a time. If the medullary centres are damaged
beyond recovery by inadequate oxygenation lasting for
several hours, then no treatment is of any avail. But
provided that it be given before this length of time has
elapsed, a blood transfusion may succeed in saving life at
any stage of the condition. Its efficacy is indeed only
limited by the actual cessation of the patient's heart beats.
I have successfully treated a patient who before transfusion
could only be described as moribund. He was almost un-
conscious, absolutely blanched, and his radial pulse
imperceptible ; his jaw was relaxed and his breathing had
become a series of fish-like gasps, such as are only associated
with imminent dissolution. His heart would certainly
have ceased beating within a few minutes, yet his condition
improved so rapidly after transfusion that an hour later it
was possible, with the help of a second transfusion, to
amputate his leg above the knee. This patient ultimately
recovered, having been as near death as it is possible to be
and yet remain alive.

22 BLOOD TRANSFUSION

The results of a blood transfusion upon a patient suffering
from acute anaemia are, indeed, amongst the most dramatic
effects to be obtained in the whole range of surgery.
Within a few minutes of its commencement the whole
aspect of the patient alters. His respiration becomes deep
and regular, his restlessness disappears, colour returns to
his face, his pulse rate falls, and he begins to take an intelli-
gent interest in his surroundings. These changes taking
place within a period of fifteen minutes may well strike an
onlooker as little short of miraculous. Shortly afterwards
the patient may fall into a natural sleep, a sure sign that
the normal circulation has been restored to the exhausted
central nervous system.

In considering how much blood should ordinarily be
given in the treatment of acute anaemia, experience is a
safer guide than any theoretical considerations. Never-
theless, it is worth while to inquire briefly into the
experimental and theoretical basis upon which the treat-
ment of acute anaemia rests. It is difficult to estimate
accurately the total quantity of blood in the body of an
adult, but it has been variously stated by physiologists to
be from a twentieth to a tenth part of the body weight, or,
in liquid measure, from 3 to 6 litres (approximately 5 to 10
pints). This has been estimated in several ways, the
results of which show some discrepancy. A figure
approaching the higher one was obtained long ago by the
direct method of washing out the blood from the bodies of
executed criminals. Recently it has been claimed by
Haldane that these determinations were inaccurate ; by
means of his carbon monoxide method, with the details
of which we are not concerned here, he has estimated that
the blood volume is but one-twentieth of the body weight,
or in very stout persons is even as low as one-thirtieth.
Still more recently Haldane's estimation has been chal-
lenged in its turn by observers who have injected a dye
into the circulation and have then determined its degree
of concentration in the blood by means of colorimetric

HEMORRHAGE AND SHOCK 23

comparisons. It is evident that if the dilution which
occurs when a known quantity of dye is injected can be
accurately estimated, then the total volume of circulating
fluid can be calculated. This method could not be used
until a non-toxic, non-diffusable dye had been discovered,
but it was found in 1915 that " vital red " fulfilled these
requirements (143). The results obtained in this way show
that those originally given by the direct method were sub-
stantially correct. The blood volume was found to vary
from 1/13 to 1/10-5 of the body weight ; on the average it
amounted to 5,350 cc, or 85 cc. per kilogram of body
weight. These observations have been in their turn
criticized (114), but only to the extent of reducing the
amount by 1/10. It may therefore be assumed that,
according to the most recent work, the blood volume is
from 5 to 6 litres, or, approximately, 8 to 10 pints.

It is a still more difficult matter for obvious reasons to
estimate how much blood a man can lose and yet remain
alive. This will depend partly on the power of physiolo-
gical accommodation possessed by the individual in his
vaso-motor system and tissue fluids and partly on the
rapidity with which the bleeding takes place. Clinical
observations have shown that after a moderate haemor-
rhage, such as the withdrawal of 800 cc. of blood from
a donor, the blood volume may be restored to normal
within an hour. If, on the other hand, the haemorrhage is
excessive, a condition results in which the normal process
of rapid restoration of volume fails, and the circulation
remains in a dangerously depleted condition. The heart
attempts to keep the blood pressure at an adequate level
by an increase in its rate, but it is in effect attempting to
circulate a small volume of fluid in a vascular system which
has become too big for it. Imperfect oxygenation of the
medullary and cerebral centres with exhaustion of the
heart results, and this is accompanied by all the symptoms
of anaemia which have been already described.

If the initial haemorrhage be very rapid, death may result

24 BLOOD TRANSFUSION

almost at once, since the physiological processes may have
no time to act. On the other hand, a rapid haemorrhage
may under certain circumstances save the patient's life,
for the immediate syncope which results produces so great
a fall in the blood pressure that haemorrhage almost ceases
and a clot may form in the lumen of the divided vessel.
If the haemorrhage be more gradual, the physiological com-
pensation may at first be adequate to maintain the blood
volume, but finally a point is reached at which this process
fails and the patient then passes into the condition of acute
anaemia.

The actual amount of blood therefore that must be lost
to be fatal will vary according to circumstances. Experi-
ence shows that haemorrhage may take place into the peri-
toneal or pleural cavities to the extent of two litres or even
more, and it may be stated as a rough guess that 2-5 litres,
that is to say, even as much as almost half the total blood
volume, may be lost without immediate death resulting.
This degree of depletion could not, however, be endured
for long. A series of clinical observations made by Keith
by the vital-red method upon the blood volume in soldiers
suffering from the combined effects of haemorrhage and
wound shock showed that in the most serious cases the
volume was below 65 per cent, of the normal, frequently
even between 50 and 60 per cent. Serious symptoms
followed a reduction to between 65 and 75 per cent. In
patients without distressing symptoms the volume was
never below 75 per cent, of the normal. There is direct
evidence, therefore, that those patients who are most in
need of treatment, such as a transfusion of blood, will
probably have lost from 25 to 50 per cent, of their blood
volume, that is to say, 1-5 to 3 litres in amount, and will
need from 750 cc. to 1-5 litres to restore them to, or near to,
the 75 per cent, level at which the compensatory processes
can begin to regain their power.

It is thus possible to arrive at a theoretical basis on which
an idea can be formed of the amount of blood that should

r

HAEMORRHAGE AND SHOCK 25

be given in acute anaemia. Practical experience is in agree-
ment with the theory, and it will now be easier to under-
stand how it is that in treating acute anaemia no attempt
need be made to replace the whole amount of blood that
has been lost, or indeed anything approaching it. In an
extreme case 2 to 3 litres of blood will have been lost and
1 litre or more will be needed to restore the blood volume
to approximately 75 per cent, of the normal. A case of
this sort, however, is fortunately not often to be met.
One has already been described on page 21 ; this patient
received altogether nearly 1,600 cc. of blood in two trans-
fusions, and 1,000 cc. of normal saline were given in
addition.

In most cases of severe haemorrhage the patient has
probably not lost more than 1,400 to 1,800 cc. of blood,
and 600 to 800 cc. will be enough to restore the balance of
the circulation. This is in practice the amoim^t of blood
that is commonly administered, and it is well within the
limits of what a single blood donor can afford to lose. If
a more definite standard be required, it may be laid down
that in a single transfusion for acute anaemia 750 cc. of
blood should be given. If, in an exceptional case, more
than this is needed, a second transfusion should be per-
formed with a similar amount taken from another donor.
Sometimes it may happen that a patient already in
exti^emis from loss of blood, needs a severe operation ; in
such a case a second transfusion may be given with great
advantage at the conclusion of the operation. The first
transfusion will restore the patient sufficiently to render
the performance of an operation possible ; the second will
combat the additional shock and haemorrhage which it has
caused. ^

It has already been stated that it was uncommon during
the war to meet with patients who were suffering from
anaemia uncomplicated by traumatic shock. It was in
fact the condition of shock which tended to dominate the
clinical picture, and it was towards the elucidation of the

26 BLOOD TRANSFUSION

facts concerning shock, its causation, prevention, and
treatment, that the investigations co-ordinated by the
Medical Research Committee were mainly directed. These
investigations were carried out both in the laboratory and
in the military hospitals, and considerable additions were
made to the knowledge of the condition. It is necessary
to give some account of the conclusions which were reached
in order that the role of blood transfusion in the treatment
of shock may be fully understood.

Haemorrhage and shock cannot be dissociated, and this
is not only because they so frequently occur together in
the same patient, but also because the manifestations of
the two conditions are essentially the same. In shock, as
in haemorrhage, are found the same pallor of the face and
mucous membranes, the same fall of blood pressure and
rapid pulse, the same perspiration, restlessness, and shallow
respiration. The symptoms following a severe haemorrhage
have sometimes been referred to as constituting a " shock-
like condition." As will be seen, however, it is more
accurate to describe the symptoms of shock as closely
resembling those of haemorrhage, and to regard both
conditions as a manifestation of deficient fluid content in
the circulation.

Numerous theories have been advanced to account for
the symptoms seen in shock. Until recent years it was
customary to suppose the vaso-motor centres had failed,
being overcome by exhaustion consequent upon excessive
stimulation by a greatly increased number of afferent
impulses from the periphery of the body. It was suggested
that as a result there was a general dilatation of the vas-
cular system, especially in the abdominal veins, and there-
fore a general impairment of the circulation. Various
hypotheses were, in addition, formulated, to account for
the vaso-motor failure. These included the ideas of
deficient carbon dioxide in the blood, exhaustion of the
adrenal secretion, and exhaustion of nerve-cells in the
higher centres. All these theories found their supporters

HEMORRHAGE AND SHOCK 27

and much experimental evidence was brought forward,
but none was susceptible of final proof. The whole theory
of vaso-dilatation and the idea that the patient " bleeds
into his own abdominal veins " were eventually disposed
of by observation of the clinical facts. Many extensive
abdominal operations have been performed upon shocked
patients, but the accumulation of blood in the splanchnic
area has never been demonstrated. It has, on the other
hand, been found that in the limbs the arteries and
arterioles are strongly contracted. It is also by no means
unusual to meet with the condition known as venospasm ;
the veins are collapsed and their walls contracted, so that
it becomes necessary to use a considerable positive pressure
before any fluid can be induced to flow into them. It has,
in addition, been shown that the vaso-motor system is still
active, and the heart, although beating rapidly, still
responds to reflex stimulation and to increase of intra-
cranial tension.

It becomes necessary, therefore, to find some other ex- j
planation of the low blood pressure which is the essential
feature of shock. Of especial value in this connexion are
the investigations by Keith, already mentioned, into the
changes in blood volume found in soldiers suffering from
shock and haemorrhage. In very few of these cases were
the symptoms due to shock alone, but usually the loss of
blood volume was much greater than could be accounted
for by the amount of haemorrhage which had taken place.
Here, therefore, was evidence strongly suggesting that the
symptoms of shock are due to actual loss of circulating
fluid, and the problem now resolved itself into a search
for this fluid which has ceased to be part of the effective
blood volume. Enough has already been said to show that
there is no evidence that the larger vessels, whether
arteries or veins, are acting as reservoirs in which the blood
is stagnating. It therefore only remains to consider
whether the capillary system is capable, under abnormal
conditions, of holding so large a proportion of the blood as

28 BLOOD TRANSFUSION

has been shown by Keith to have left the circulation. For
a discussion of this problem the reader may be referred to
W. B. Cannon's summary of the arguments (45), from which
it becomes clear that the capillary system may be regarded
as a potential reservoir large enough to contain the lost
blood in shock. The question is, however, further
complicated by the fact that the capillary blood in shock
differs from the circulating blood in containing an abnormal
concentration of corpuscles. Extensive observations made
on wounded soldiers have shown that the number of red
blood cells may rise even to 8,000,000 per cmm. in the
capillary blood, while the number in the venous blood
remains at 5,500,000 or less. This concentration of the
red cells is gradual and progressive, and will by itself
account for a large part of the loss of volume, since normally
the bulk of the blood is made up of corpuscles and plasma
in approximately equal parts. The stagnation is, more-
over, accentuated by the increased viscosity of the blood
resulting from the concentration, and by the chilling of
the surface of the body, which is always a feature of the
state of shock. A vicious circle is thus established, and
the symptoms of shock become severe as the capillary
stagnation becomes more pronounced.

A second factor which may also play its part in the loss
of blood volume in the general circulation is the exudation
of some of the plasma into the surrounding tissue spaces.
As the stagnation increases, oxygenation decreases, and the
walls and the capillaries become more permeable, so that
some fluid is probably lost in this way. This permeability
may also be accentuated by the increased hydrogen- ion
concentration in the blood, which often accompanies
shock, but it seems to be clear that this is a secondary
phenomenon resulting from imperfect oxygenation in the
tissues, and it will therefore not be regarded as one of the
factors responsible for shock. Further fluid is lost by the
copious perspiration commonly seen in shock. There
seems, therefore, to be a conspiracy between a whole set of

HEMORRHAGE AND SHOCK 29

different factors all tending to deprive the patient of his
circulating fluid. The net result is a condition so closely
resembling haemorrhage that it may be impossible to
distinguish the two, this difficulty being increased by the
fact that they so often occur together.

In the foregoing account of the production of shock the
fate of the lost blood has been discussed, but nothing has
been said of the factors initiating the capillary stagnation.
This is a subject which is of great interest and some
obscurity, and is of evident importance in considering how
shock may be avoided. The present treatise, however, is
primarily concerned with the treatment of shock when
already established, and it is therefore not proposed to
follow out the other question in detail. An injury may be
followed immediately by a condition of " primary wound
shock," in which the patient becomes suddenly pale and
pulseless. This is a physiological reaction, which may be
transient, and it is to be distinguished from the much
more serious condition of " secondary wound shock "
which appears some time later. It is this secondary shock
alone which has been under consideration in the preceding
pages. The chief importance of the primary shock lies in
the fact that it may initiate the conditions which predis-
pose to secondary shock, so that under certain circum-
stances the one may become merged in the other. These
predisposing conditions are ii^creased evaporation from
the skin, a general fall in the temperature of the body,
mental anxiety, and the continued stimulation of the
higher centres by afferent impulses as is manifested by
pain. The condition of secondary wound shock was
shown in a striking degree, during the earlier years of the
war, by the men suffering from fracture of the femur. In
the later part of the war warmth was supplied more
systematically than before to the seriously wounded, and
all fractured femurs were treated at an early stage with
Thomas's splints. Two of the factors predisposing to
shock, namely cold and pain, were in this way to some

30 BLOOD TRANSFUSION

extent eliminated, and it was very striking how much better
than before was the general condition of the patients on
arrival at the hospitals.

Nevertheless, the elimination of these factors, which is
a simpler matter in civil life than it was under conditions
of war, will not avert all shock in a large proportion of
cases. It is necessary, therefore, to find some additional
factor which will initiate shock in addition to the predis-
posing causes. It is thought that this may have been
identified in a substance of obscure nature which is derived
from the damaged tissues themselves, and which, circulating
in the blood, is able directly to affect the capillary system.
Just as the shock following severe burns is believed to be
due to the circulation of a toxic substance formed by the
burning of the skin and other tissues, so the shock following
severe trauma is believed to be of toxic origin, the toxin
being derived from damaged tissues, muscle being parti-
cularly active in this respect. The condition may, there-
fore, be one of " traumatic toxaemia," in which there is a
general loss of capillary tone throughout the body, so that
" the blood percolates into the network of channels as into
a sponge." The circulating blood is thus rapidly depleted,
and the symptoms of shock become established. The
investigation of this source of shock was carried out
chiefly by Dale, Bayliss and Cannon (65), who were
able to reproduce the condition of shock in animals
by the injection into their circulation of a substance
obtained from damaged muscles. To this substance
the name histamine was given. It would be a mistake,
however, to suppose that because a substance producing
shock experimentally has been obtained from muscles, that
therefore this is the identical substance which is responsible
for every case of traumatic toxsemia. Extreme shock may
be produced when but little damage has been done to
muscles. Probably damage to any tissue of the body if
extensive enough will produce a substance or substances
which will give rise to the symptoms, and it may be a long

r

HEMORRHAGE AND SHOCK 31

time before these are isolated and identified. That the
last word on the production of shock is still far from being
uttered is shown by the fact that profound shock may be
induced without doing any appreciable damage to tissue,
namely, by handling and exposing the abdominal viscera.

It may be this traumatic toxaemia which will account for
many cases of post-operative shock, but it has been shown
that some anaesthetics, such as chloroform or ether, will of
themselves greatly accentuate shock initiated by other
causes.

It has already been mentioned that the increased hydro-
gen-ion concentration in the blood, which results from
imperfect oxygenation in the tissues, is not itself a cause
of shock, but it will aggravate shock due to other factors.
A discussion of this will be found in the paper by W. B.
Cannon already referred to.

The present state of knowledge concerning the causation
of shock having been thus briefly reviewed, the question
of the treatnient of the condition may be discussed. In
this connexion the value of blood transfusion will be
considered. It will have become clear that essentially the
condition to be combated in treating shock is one of
lowered blood pressure following upon a diminution of the
volume of blood in the circulation. All the factors which
have been mentioned in considering the causation of shock
must be combated. Warmth must be supplied, morphia
administered, fractures efficiently immobilized, damaged
tissues excised : but clearly all these measures are
prophylactic rather than curative. None of them will
remove a state of profound shock once established, for they
will not of themselves restore the blood volume depleted
by capillary stasis. It is necessary, therefore, to attack
this condition directly. It may with justice be compared
to a state of acute anaemia following haemorrhage, but with
this difference, that the blood is still present in the body and
will return to the circulation when the capillary stasis has
been abolished and the circulating balance has been

a^ BLOOD TRANSFUSION

restored. The possibility of recovery from shock depends
upon how long the condition has existed. After a certain
time the toxaemia, whether the primary traumatic toxsemia
or the secondary increase in hydrogen-ion concentration,
appears to have a damaging effect upon the capillary walls,
so that an increased loss of fluid takes place into the tissues
and this cannot be remedied. It is essential, therefore, to
use the means which will most rapidly restore the circula-
tion and bring about a rise in blood pressure which will be
permanent. It is reasonable to infer that the most hopeful
means of bringing this about is by a blood transfusion,
which will actually replace the blood temporarily lost.
This is the physiological remedy, and its value has been
proved by the results obtained in many cases of my own as
well as in those recorded by others. The efficiency of the
treatment is accentuated by the fact that so large a pro-
portion of cases of shock are associated with, and aggra-
vated by, some degree of haemorrhage. Apart from this,
Keith's observations have shown that the diminution of
blood volume in shock is comparable with that which
attends severe haemorrhage. The state of shock in fact so
closely resembles haemorrhage that most of the same
remarks concerning blood volume and the amounts that
should be given by transfusion may be applied, and it is
unnecessary to repeat them here. It must be remembered,
however, that in pure shock the amount of haemoglobin in
the body is not reduced though there is less in the circula-
tion. It is restored to the circulation when the capillary
stagnation is overcome. This will be referred to again
later on.

During the war the value of blood transfusion in shock
was amply demonstrated. In civilian practice I have
found it to be of value when given after operations such as
removal of the rectum, whether by the perineal or abdomino-
perineal route, amputation of the leg through the hip joint,
or removal of a sarcoma from the nasopharynx. Trans-
fusion should be given towards the close of the operation

HEMORRHAGE AND SHOCK 33

before the evidences of shock have reached their maximum.
The depletion of the blood volume is then actually remedied
as it takes place, and transfusion becomes almost as much
a prophylactic measure as warmth and the administration
of morphia.

It is probable that the mortality following very severe
operations such as those mentioned above would be con-
siderably reduced if blood transfusion were to be given as
a routine measure. Reference has already been made to
the bad effect of the ordinary anaesthetics, and the best
effects are obtained by a blood transfusion in conjunction
with gas and oxygen or with spinal anaesthesia. It is
necessary, however, to draw attention to the fact that a
blood transfusion if given to a patient under the influence
of a spinal anaesthetic must not be performed until the
operation is very nearly completed, for it will very often
produce a much more rapid return of sensation than would
otherwise occur.

In advocating the use of blood transfusion to combat the
effects of shock and haemorrhage, it would be misleading to
imply that this is necessarily the only treatment that is
available. Something must be said of the substitutes for
blood that have been used, and in particular the value of
gum acacia must be considered. In the days before the war
it was customary to treat post-operative shock or haemor-
rhage with large quantities of normal salt solution given
intravenously or subcutaneously. During the earlier part
of the war also this was used, and there can be no doubt
that for the less severe cases this treatment is often bene-
ficial. Occasionally even the lives of patients who were
desperately ill have been saved by it ; I have seen a saline
infusion cause the recovery of a man who had a dozen
perforations of the small intestine and who had, in addition,
lost several pints of blood intraperitoneally from a wound
of a large mesenteric vessel. Such cases are, however,
exceptional. In the presence of severe shock or haemor-
rhage a saline infusion may cause an immediate rise in

^4 BLOOD TRANSFUSION

blood pressure, but the fluid exudes so rapidly into the
tissues that the effect is usually very transient. This,
fact is universally admitted to be true and need not be
further emphasized. Saline solution administered by the
rectum is likely to have a more lasting effect, but the
process of absorption is slow, and the patient may be dead
before it has had time to act. The same applies to water
given by the mouth. A patient suffering from severe
shock is unable to tolerate more than a very small quantity
of fluid in his stomach without vomiting. Some success
was attained by Oswald Robertson in treating cases of
haemorrhage by the method of " forced fluids," large
quantities being given by the mouth and by the rectum (245).
In many serious cases, however, this treatment is inappli-
cable, and it is clear that transfusion is more rapid and
more certain in its effect. Isotonic saline having been
found ineffectual, it was suggested that a hypertonic
solution (2 per cent, sodium chloride) might be of more
value. This was tested clinically and in the laboratory,
and was found to have no advantage over the isotonic
solution (11).

When the association of increased hydrogen-ion con-
centration with shock was demonstrated, it was at first
supposed to be one of the factors producing the condition.
It was therefore natural that the effect of a solution of
sodium bicarbonate (4 per cent.) should be tried. The
effect upon certain cases suffering from extreme
" acidosis " and air hunger was very striking, but in
general the alkaline solution was no more effective than
the ordinary isotonic saline. I soon abandoned its use
for intravenous infusion, but it was of service in serious
cases when given by the rectum.

During the war the necessity for the conservation of
time — and of blood — ^was evident. The search for a
satisfactory substitute for blood was therefore prosecuted
with great energy, most of the research being done by, or
under the direction of. Professor W. M. Bayliss. The

r

HEMORRHAGE AND SHOCK 35

object of the research was to discover a non-toxic solution
which possessed the same " viscosity " as the blood, and
the same osmotic pressure due to contained colloid. It was
believed that such a solution would not tend to exude so
rapidly into the tissues and would therefore augment the
blood volume more effectively than the fluids previously
used. After many experiments it was claimed in 1916
that a blood substitute had been found in a 6 per cent,
solution of gum acacia with -9 per cent, sodium chloride.
It was even stated on the evidence of laboratory experi-
ments that the gum solution was as effective as blood in
the treatment of shock and haemorrhage. It was therefore
used very extensively among the wounded, and favourable
reports upon its value were made by various workers. It
is difficult, however, to control the results in giving treat-
ment of this kind. If a patient dies after being given a
gum infusion, no one can state definitely that he would
have lived had he been given a blood transfusion instead.
If a patient lived after having a blood transfusion, it would
be equally rash to state that he would have died had he
been given gum. Nevertheless, after giving the gum
solution a number of trials, I formed the opinion that the
results were inferior to those obtained with blood. Patients
did not recover whom from previous experience with blood
transfusion I should have expected to do so. I accordingly
continued to use blood in preference to gum whenever it
was available, although justice must be done to those who
so strongly advocated gum by saying that there can be no
doubt that it is very much more effective than other
solutions previously used. The same opinion was formed
by many other surgeons, although it was natural to feel
a bias in favour of gum which could be given with much
greater economy of time and effort than blood. Up to
the present time I have seen no reason for altering this
opinion, and should always prefer to treat haemorrhage and
shock with a blood transfusion if possible.

Recently the relative values of a number of intravenous

36 BLOOD TRANSFUSION

infusions for shock have been put to an extensive experi-
mental test by F. C. Mann. The shock was produced by
handling the abdominal contents, and the effect on the blood
pressure of the various fluids was mechanically registered.
The conclusion was reached that far the best results were
obtained by a transfusion of blood or blood serum, the
effect of these being more permanent than that of any other
substance used. The use of gum acacia was found to give
results which were " variable and sometimes disastrous,"
but this may have been due to some extent to errors in the
technique of preparing the solution.

This draws attention to a possible objection to the use
of gum, namely, that some samples of the solution have
been found to be actually toxic ; but it is said that this can
be avoided if proper care be exercised in its preparation.
Full instructions for this are given in a paper by S. V.
Telfer.

Into the discussion of the relative merits of blood and
gum solutions may be profitably introduced the further
question as to which is the more valuable constituent of
transfused blood, the corpuscles or the plasma. It has
been seen that the essential factor in producing the
symptoms of shock and haemorrhage is a reduction of blood
volume, and treatment is therefore directed in the first
place towards the restoration of this volume, with a fluid
of the same viscosity and osmotic pressure as blood. This
might be done with plasma or, some may say, equally well
with gum. From the point of view only of volume, the
corpuscles and plasma are of equal value, since each forms
approximately half the total volume of a given quantity
of blood. There is, however, another aspect to be con-
sidered. One of the results of loss of blood volume is
imperfect oxygenation in the tissues. When the volume
is increased by the addition of plasma or gum, the corpuscles
in the circulation are diluted, and this by itself would tend
further to impair oxygenation. The dilution is, however,
compensated for by the improvement in circulation which

HEMORRHAGE AND SHOCK 37

in its turn improves the supply of oxygen to the tissues,
and it is still further counteracted by the restoration to the
circulation of the blood corpuscles which were stagnating
in the capillary system. It seems clear that these
successive processes will be accelerated by the use of a
fluid which itself contains corpuscles, and this may afford
a theoretical explanation of the clinical observation that
blood is more effective than gum. Its use will tend to
establish more quickly the " virtuous circle " following
increased volume, and so undo the " vicious circle " due
to insufficient volume. It has been questioned whether
the corpuscles of transfused blood really do play an active
part in the economy of their new host, or whether their
new environment may not quickly render them effete.
This has been answered by the exceedingly interesting and
ingenious series of experiments carried out by Winifred
Ashby. She has transfused blood of a known group (see
Chapter IV) into an individual of a different, but compatible
group, and then shown that it is possible by selective
agglutination with a suitable serum to demonstrate the
presence m the blood of the two kinds of corpuscles side
by side. In this way she has shown that transfused cor-
puscles are still present in the circulation and of normal
appearance thirty days after they were introduced.

It is therefore justifiable to make the inference that
transfused corpuscles can for some little time carry out
their normal function. If it be true that their presence is
an advantage in the treatment of deficient blood volume,
it may also be conjectured that their presence is likely to
be of greater importance in treating haemorrhage than it
is in the treatment of pure shock, for in the latter condition
all the original corpuscles are still present in the body,
while in the former they are not.

I should sum up the discussion of the relative merits of
blood and gum by saying that on the groimds of experi-
ment and clinical experience I believe blood to be the
more efficient of the two, particularly in the most serious

38 BLOOD TRANSFUSION

cases. Every patient who needs it should therefore have
the advantages conferred by blood transfusion if it can be
done. If it cannot, then gum and saline is much the most
satisfactory substitute that is at present known.

Some of the concluding remarks in the foregoing pages
will have suggested that the use of gum infusion may be
considered of more value in treating pure shock than in
treating haemorrhage. For this reason, apart from other
diagnostic considerations, it may be of importance to
be able to distinguish clinically between shock and
haemorrhage. Attention has already been drawn to the
fact that the symptoms and appearance seen in a patient
suffering from severe shock very closely resemble those
seen in haemorrhage. It may, in fact, be impossible to
say from purely clinical evidence whether a patient is
suffering from shock, or haemorrhage, or both. A case
which recently came under my own observation well
illustrates this point. A very stout, elderly man had
fallen down a lift-shaft and was brought into St. Bartholo-
mew's Hospital soon after the accident. He appeared
to have fallen on his feet, and the lower ends of both tibiae
had been driven through the inner sides of his soles, but
there were no other signs of injury. His general condition
on arrival at hospital was fairly good, but all the usual
measures were taken to minimize shock. An hour or two
later he had passed into a condition of extreme collapse,
and exhibited all the symptoms which have already been
described. Not much haemorrhage had taken place from
the wounds in his feet, and the question arose as to whether
his present condition was due to internal haemorrhage from
visceral injury, or whether it was due chiefly to shock.
His abdomen contained so much fat that no evidence could
be obtained from an examination of it, and it was in fact
impossible to arrive at any conclusion. There could, how-
ever, be no question of performing any operation, and the
patient made no response to other treatment. At the
autopsy it was found that there were fractures of the ribs,

HEMORRHAGE AND SHOCK 39

r

■ spinal column, and symphysis pubis in addition to the
K injuries to the legs. There was very little haemorrhage in
^P connexion with any of the fractures, and it appeared that
death was to be attributed almost entirely to shock. This
was perhaps a somewhat unusual case, in which no help
could be derived from an examination of the patient, but
similar difficulties will sometimes be met.

It might be expected that a criterion would be supplied
by an examination of the blood. The results from this,
however, have proved to be disappointing. The facts have
^k been investigated by Cannon and others (47) and may be
^^ summarized as follows. The number of red corpuscles in
the blood from the capillaries of the ear or finger has been
found to be invariably raised in patients suffering from
shock. A blood count may show an increase up to seven
million red cells per cmm. or even more. The blood in the
venous circulation, however, of the same patient is more
dilute, the count being less by one to two million red cells.
When the shock is complicated by haemorrhage, the blood
count in the venous system will again be lower than that
in the capillaries, but in both the counts will be less than if
there were no haemorrhage. The differences are, however,
not so great or so constant that any principle can be laid
down by which the two conditions may be distinguished.
In patients in whom haemorrhage is the outstanding feature
the blood counts will be still lower, but the capillary and
venous difference will still be present. It was found that
in haemorrhage the haemoglobin percentage, and therefore
the colour index, tended to be lower than in shock, but this
was most obvious when the haemorrhage had been very
severe, and in such cases the diagnosis is usually clear
from other evidences. The clinical difficulty lies in the
distinction between cases of pure shock and of shock
complicated by considerable haemorrhage. It seems that
little help is to be derived from an examination of the
blood. This difficulty in diagnosis can only influence
treatment in the direction of giving blood rather than

40 BLOOD TRANSFUSION

gum-saline, though the latter would probably be effective
for many of the cases of shock if they could be distin-
guished.

The effects of transfusion for haemorrhage and shock
are to be judged best by the clinical results. The abnormal
distribution of the corpuscles is altered by the treatment
with a consequent redistribution in the circulation. No
constant changes, therefore, in the blood count follow
transfusion, and no exact mathematical effect can be
demonstrated. It has been shown by Huck that some-
times the immediate rise in the blood count is greater than
can be accounted for by the amount of blood given. This
is often followed by a fall, which is succeeded in its turn by
a second rise. These results are to be explained by altera-
tions in the amount of destruction and formation of red
cells going on in the body. That is to say, they are
biological rather than mechanical, and are at present but
imperfectly understood.

In the foregoing discussion haemorrhage and si ock have
been considered in a general way. Something i lUst now
be said of the particular conditions for which transfusion
may be given. Concerning traumatic haemorrhage and
shock there is little to be added, for these conditions present
the general features of the problem in its least complicated
form. No clear-cut rule can be laid down as to the point
at which transfusion becomes necessary. The blood
pressure is perhaps the best single indication, and if this
has fallen below 80 mm. (systolic), then a transfusion is
certainly indicated. Apart from this, the patient's general
condition is the safest guide. As soon as it becomes
evident that his life is in danger, a transfusion should be
given. Better save a few lives by many transfusions than
lose them by reserving transfusion for those who are
actually moribund.

Secondary haemorrhage following an operation is funda-
mentally similar to primary haemorrhage, but may present
a few additional points. In recent years by far the largest

HEMORRHAGE AND SHOCK 41

number of transfusions for secondary haemorrhage have
been given for bleeding from septic amputation stumps.
In many cases of this sort it is no easy matter to stop the
bleeding by ligaturing a bleeding vessel ; sometimes it is
impossible. Nevertheless, transfusion should not be with-
held owing to a risk of increased haemorrhage supposed to
follow a rise in blood pressure. Usually the patient is
debilitated by prolonged suppuration, and often his blood
is deficient in its power of coagulation. It has been found
that a transfusion, in addition to replacing some of the
blood that has been lost, tends to improve the patient's
resistance to micro-organisms, and to shorten the coagula-
tion time of the blood. Recurrence of the haemorrhage is
therefore discouraged on the whole, and in many cases a
series of transfusions for recurrent haemorrhages has saved
a patient's life when the prognosis had seemed to be almost
hopeless.

Post-operative haemorrhage associated with chronic
jaundice is another condition which demands special
consideration ; this will be dealt with later under the
heading of haemorrhagic diseases.

The proper treatment of severe haemorrhage from a
gastric or duodenal ulcer has always puzzled physicians
and surgeons alike. It is probably true that patients very
seldom die as the result of a single rapid haemorrhage, even
if severe. There can, however, be no doubt that death
due actually to acute anaemia may follow repeated or pro-
longed haemorrhage. Hitherto treatment has been con-
ducted mainly on medical lines. Opinion is now, however,
tending to favour earlier and more frequent surgical inter-
ference, and this can be made a less dangerous procedure
by giving a preliminary blood transfusion to improve the
patient's general condition. When the patient's life is
threatened by haemorrhage repeated or prolonged, trans-
fusion is undoubtedly the best means of saving him. Here
again the fear of restarting the haemorrhage by raising the
blood pressure has acted as a deterrent, so that transfusion

42 BLOOD TRANSFUSION

is apt to be withheld until too late. Nevertheless, it is clear
from the numerous cases recorded in the literature that this
fear is groundless (130, 215, etc.). The effect of a transfusion
on the coagulating power of the patient's blood more than
compensates for the risk attending a rise in blood pressure.
Now only is lost blood replaced, but also the clot plugging
the damaged vessel is made more secure. The patient is
tided over the immediate danger to his life, and surgical
treatment is made possible. This view will doubtless
meet with much adverse criticism, but its justice will
eventually be recognized.

As in the early days of transfusion, so at the present
time, a considerable proportion of the patients that need
transfusion will be met with in the course of obstetrical
practice. It has often been remarked how much blood can
be lost by a woman following the delivery of her child
without any serious result ; nevertheless, many deaths
are occasioned every year by post-partum haemorrhage,
placenta prsevia, and rupture of an ectopic gestation.
Sometimes the bleeding is so rapid that there is no margin
of time available for a transfusion unless all the facilities
be immediately at hand. Short of this, transfusion is the
ideal treatment, and the problem is a simple one, the relief
of acute anaemia being the only object in view. One
interesting modification of the procedure has been recently
recommended by German writers, namely, the reinfusion
of the patient's own blood. This is applicable only when
the haemorrhage has taken place into the peritoneal cavity,
and is therefore limited to the treatment of a ruptured
liver or spleen, a ruptured uterus, or a tubal abortion.
With a ruptured uterus the sterility of the blood is not
assured, and this condition were better not included. For
the other conditions Lichtenstein recommends that the
blood should be ladled out of the peritoneal cavity into
Ringer's solution and then strained to remove clots. The
resulting fluid is infused into a vein. Judging from my
own experience of intraperitoneal haemorrhage, not much

HEMORRHAGE AND SHOCK

43

blood would actually be recovered in this way, since
usually so much of it has clotted. In any case, the whole
procedure is to be looked upon with suspicion owing to the
unknown and probably profound changes that have taken
place in partially clotted blood. Eberle records that in
one case re infusion was followed by haemolysis, and among
twenty-one cases reported by Schweitzer in 1921, one death
was attributed to the reinfusion, which, as in Eberle's
case, was followed by haemoglobinuria. Transfusion has
also been used for the toxaemias of pregnancy, but this will
be dealt with under another heading.

CHAPTER III

INDICATIONS FOR BLOOD TRANSFUSION — Continued

HEMORRHAGIC DISEASES

It is claimed that blood transfusion provides an efficient
means of treatment in most conditions distinguished by
symptoms of spontaneous haemorrhage or by traumatic
haemorrhage which cannot be controlled. All such diseases
have the common features that the coagulation time of
the blood is abnormally prolonged, and it may be supposed
that the transfused blood supplies some missing constituent,
so that for the time the blood is enabled to coagulate more
normally. Most of the evidence available shows that the
claims made for transfusion are not exaggerated.

Jaundice. — It is well known how exceedingly dangerous
an operation upon a jaundiced patient may be owing to
the difficulty of obtaining haemostasis. The coagulation
time of the patient's blood is not affected in a transient
catarrhal jaundice, but in the chronic condition it has been
shown to be three or four times the normal (223). In these
circumstances it is found that a transfusion is of some
use in shortening the coagulation time of the patient's
blood so that bleeding ceases, although sometimes,
especially in cases of jaundice due to malignant disease in
which the biliary obstruction has not been relieved by the
operation, the effect is very transitory, and after two or
three days the patient may again begin to bleed (215).
No other method of overcoming this has yet been fomid to
be more effective than transfusion, though the intravenous
administration of calcium compounds is sometimes of value.

44

HEMORRHAGIC DISEASES 45

Haemophilia. — Blood transfusion is of still greater value
when the coagulation time of the blood is prolonged owing
to a congenital deficiency, as in haemophilia. It is un-
necessary to discuss here in detail the precise nature of the
deficiency. No definite conclusion has yet been reached,
though it seems to be clear that the abnormality resides in
the organic clotting complex, and not in the calcium content
of the blood. Treatment, therefore, will aim at supplying
the deficient substance, so that the coagulation time may
be reduced to normal, whereupon the bleeding will cease.
Various methods of bringing this about have been used.
Horse serum or whole blood injected subcutaneously has
often been found effective and sometimes even when used
merely as a local application. Not infrequently, however,
horse serum fails of its effect, so that no reliance can be
placed upon it. Even when effective, the alteration in
coagulation time is transitory, a fact which introduces an
obvious objection to its use, for if the occasion should arise,
as it easily may, for a repetition of the treatment, the
patient may be exposed to the risk of severe anaphylactic
shock.

Another form of treatment has been introduced by
H. W. C. Vines, in which a slight anaphylactic shock is
deliberately induced, the result of this being a fall in the
coagulation time of the blood to normal. The mechanism
of this change is at present unexplained. Again, the effect
is transitory, but for a certain period afterwards a surgical
operation may be safely performed upon a haemophilic
patient treated in this way. This method has not yet
been extensively tested, and in any case it cannot be used
in an emergency, for the patient must be sensitized by a
preliminary injection and an interval of several days allowed
to elapse before the anaphylaxis can be produced.

The efficiency of blood transfusion in the treatment of
haemophilia has been very often demonstrated, and seems
at present to afford the most certain means that we possess
of arresting the symptoms. Presumably the transfused

46 BLOOD TRANSFUSION

blood supplies directly the deficient factor in the coagula-
tion complex, and it has been shown by Bernheim (1917)
that the transfusion even of quite a small amount of blood
will almost immediately stop the bleeding. In addition
to comparative certainty and rapidity in action, transfusion
has the advantage that it will replace the blood which has
been lost, for often the patient has reached a stage at which
he is in danger of his life from actual anaemia. This
treatment, therefore, will always be useful in an emergency,
whether the patient be bleeding to death from a slight
wound, or whether he be suffering from acute appendicitis
and so is in need of an immediate operation. If trans-
fusion does not at once stop the bleeding, the treatment
can be repeated, so that the patient should not be allowed
to die from loss of blood. In most cases the bleeding will
eventually stop if the patient's life can be prolonged.
Even if the treatment be immediately successful, the trans-
fused blood necessarily contains only a limited quantity
of the substance necessary for the coagulation complex,
and this gradually disappears. Again, therefore, the effect
is transitory, so that transfusion is in no sense curative.
It has been noticed that the tendency of a haemophilic to
bleed decreases as age advances, and it has been suggested
by Ottenberg and Libmann that small quantities of blood
should be injected into his veins at regular intervals of one
to three months. It is possible that in this way he might
be brought safely through the more perilous years of his
life.

The proof of the effect of transfusion upon the coagula-
tion time of the blood rests upon the evidence of a number
of independent observers. Pemberton has recorded a case
of a haemophilic whose coagulation time before transfusion
was estimated to be 23 minutes. Blood was given to the
amount of 500 cc, and 5 minutes later the coagulation
time was 3 minutes. Twelve hours later it was 8 minutes,
and on the fourth day after transfusion it had risen again
to 20 minutes.

HEMORRHAGIC DISEASES

Other observations have been made as follows

47

Coagulation time.

Minutes.

Bulger

Before transfusion
1 day after transfusion
8 days „

25 „ „

82

10

8

40

Minot & Lee

Before transfusion

After

3 days after transfusion

150

normal

60

100

Addis .

Before transfusion
After „
25 days after transfusion
After 8 cc. serum injected

245
24

200
38

In treating jaundice or haemophilia the transfusion may
be performed by the method of choice described in Chapter
VII of the present work. The addition of an anticoagulant
to the blood does not render it any less efficient as a haemo-
static agent. In all cases the coagulation time of the
patient's blood is found to be reduced after transfusion,
whether sodium citrate be used as an anticoagulant or
not. The explanation of this may be found in the fact
referred to on p. 120, that the citrate is very rapidly
destroyed in the circulation, and so cannot for long
influence adversely the haemostatic properties of normal
blood.

The seeming paradox of using an anticoagulant in an
endeavour to promote the coagulation of the blood is
heightened by the work of Ottenberg, who has shown that
the coagulation time may be reduced by the intravenous
injection of sodium citrate alone. In this experiment 20
cc. of a 3 per cent, solution of sodium citrate were injected
into a haemophilic, whose coagulation time had been found
to be 85 minutes. Ten minutes after the injection it was
found to be 25 minutes. Two days later it had risen again

48 BLOOD TRANSFUSION

to 85 minutes. This observation has not been confirmed^
but, if it be true, citrated blood is likely to be actually
more efficient in the treatment of hsemophilia than un-
treated blood.

The amount of blood to be transfused in hsemophilia
will vary with the age of the patient and according to
whether he is suffering from acute anaemia or not. If
haemostatic effects only are wanted, 100 cc. of blood will
be enough. If anaemia is also present, the dosage will
be governed by the same considerations as have already
been discussed in the section on the treatment of
haemorrhage.

Melaena Neonatorum. — Another haemorrhagic con-
dition in which blood transfusion is of the very greatest
value is that known as melcena neonatorum. Severe
haemorrhage takes place from the bowel of an infant,
sometimes only a few hours after birth. The cause is
quite unknown, but it is found that absolute haemostasis
is usually brought about by blood transfusion. Horse
serum has often been successfully used as in treating
haemophilia, but blood transfusion again has the additional
merit that the blood which has been lost is thereby re-
placed. A single transfusion is usually enough, as the
haemorrhage does not tend to recur when once it has been
stopped. For a newly born infant, even if in extremis,
only a small quantity of blood is needed, so that a trans-
fusion of 50 to 100 cc. is usually found to be enough.
Bruce Robertson suggests that, as a good working rule,
the amount should not exceed 15 ccm. per pound of body
weight. The superficial veins of an infant are exceedingly
small, so that the introduction even of a fine needle into
the median basilic may be matter of the greatest difficulty.
The best method of transfusing an infant, therefore,
demands special consideration. A description of this will
be found on p. 134 of the present work.

The value of transfusion for melcena neonatorum has not
been very generally recognized, but a number of striking

H-^MORRHAGIC DISEASES 49

cases have been reported. Defibrinated blood had been
used in 1873 by Sir Thomas Smith as described in Chapter
I, but the first case in which whole blood was used was
published by Lambert in 1908. Later, in 1910, Welch,
and then Schloss, recommended the subcutaneous injection
of serum or of blood, but these measures were clearly not
so effective as the intravenous transfusion of blood, as
has been testified by numerous observers (Lespinasse,
Unger, Vincent, Graham, Bruce Robertson, Lapage,
Hutchinson, etc.). The patients may be actually mori-
bund, for a new-born infant can only afford to lose a
relatively small amount of blood, but even then transfusion
is often successful. Bruce Robertson reports that of a
series of forty cases of hsemorrhagic disease of the new-
born which were treated by transfusion, all recovere'd
except four ; of these two died from associated umbilical
sepsis, one from intracranial haemorrhage, and the fourth
had already ceased breathing when the treatment was
begun.

It has sometimes been stated that for transfusing an
infant either parent can be safely used as blood donor, on
the assumption that the serum reactions are not yet
developed. This may sometimes be true, but the fallacies
and possible dangers of this are explained in a later chapter.

A case was recently reported by R. D. Laurie, who,
knowing that he himself belonged to Group IV, drew 20
ccm. of his own blood into a syringe containing five grains
of sodium citrate in solution. This he injected into a
vein in the infant's arm ; the small size of the vein he had
chosen made this difficult, but the treatment resulted in
the rapid recovery of the patient.

Purpura. — Of all the forms of haemorrhagic diseases, the
two already described, haemophilia and melaena neonatorum,
are the only ones for which blood transfusion is a really
effective remedy. It is probable that under the somewhat
general term " purpura haemorrhagica " are grouped
several conditions, all of very obscure origin, none of
4

50 BLOOD TRANSFUSION

which are conspicuously benefited by transfusion. Many
transfusions have been given for purpuric symptoms,
chiefly in America. Several cases are reported by Bern-
heim, and twelve transfusions were given to seven patients
by Peterson. In some of these the treatment produced a
temporary improvement, but usually they relapsed after
an interval of a few months. One of Bernheim's patients
appears to have owed his life for the time being to a
transfusion, but he died subsequently during a recurrence.
Two cases are reported by Graham. One was not bene-
fited at all ; the other improved for a time, but afterwards
relapsed. In a serious case, therefore, transfusion may
be worth trying ; it has indeed been stated by Ottenberg
and Libmann, observers with a wide experience of trans-
fusion, that this treatment is " definitely curative " in
severe cases of purpura. At the present time there is
little to add on the subject, but it is possible that further
advances will be made by proceeding on these lines.

Blood Diseases

Pernicious Anaemia. — Blood transfusion has been
advocated for several conditions characterized by altera-
tions in the cells of the patient's blood. It has been used
in the treatment of aplastic anaemia, splenic anaemia,
chlorosis, and leukaemia, but in none of these diseases has
it been of much avail. In pernicious anaemia, however,
transfusion has proved to be of very great service.

It is, indeed, now a recognized form of treatment for
this disease, though the numerous reports upon results
that have been published have not pronounced unanimously
in its favour. Variability in results probably depends to
some extent upon the difficulty of distinguishing true
pernicious anaemia from some forms of secondary anaemia.
It is hardly to be expected that much benefit w^ould follow
blood transfusion in the undiagnosed secondary type,
since the destruction or loss of corpuscles is continuous

r

BLOOD DISEASES 51

until the cause has been removed. In true pernicious
anaemia, on the other hand, there may be remissions in the
disease, and it is quite clear that these may be initiated or
prolonged by blood transfusion. The largest number of
consecutive cases that has been recorded was treated in
the Mayo Clinic in the years 1915 to 1918 (Archibald,
Pemberton, Hunt). It was estimated that in about 60
per cent, of the patients with pernicious anaemia a definite
improvement followed transfusion. It is generally agreed
that the best results are seen in those who have not yet
reached the last stages of the disease, though sometimes
patients who are actually in extremis will also show great
improvement. A remarkable instance of this has been
reported in Norway (261). A man, aged thirty-three, was
dyspnoeic, semi-conscious, and moribmid when admitted to
hospital. His red cells numbered 850,000 per cmm., and
his haemoglobin percentage was 19. Immediate improve-
ment followed the transfusion of 900 cc. of cit rated blood,
the red cells rising quickly to 2,000,000 and later to
3,000,000. Twelve days after admission he was walking
about. No case must therefore be regarded as hopeless,
though disappointments must be expected.

As a general rule blood transfusion should be given
before the more serious secondary manifestations of the
disease have shown themselves, that is to say, some time
before the condition has become dangerous to life. Pro-
bably the disappointing results of this treatment have
partly been due to the fact that it has been regarded as a
last resort and has often been given at too late a stage.
No rule can be laid down as to when transfusion should
be given, but common sense suggests that it should be tried
as soon as it is evident that the disease is progressing in
spite of other methods of treatment. One authority
(Anders) even advises that transfusions should be given as
soon as an assured diagnosis has been made, but he weakens
his case by adding that other methods of treatment should
be used at the same time. If the patient is already seriously

52 BLOOD TRANSFUSION

ill when first seen, the blood transfusion should be tried
at once, as its effect, if beneficial, is likely to be more rapid
than that of any other form of treatment.

The amounts of blood given in pernicious anaemia have
varied. Massive doses have occasionally been given (179),
but the general opinion seems to favour smaller amounts, 300-
500 cc, the dose being repeated at intervals of two or three
weeks. Repeated transfusions have been an outstanding
feature of the treatment, and as many as thirty-five trans-
fusions of 500 cc. or more have been given to one patient,
extending over a period of thirty months. This is in itself
a demonstration of the fact that blood transfusion does not
cure the disease ; the beneficial effect of each transfusion
may wear off in a short time, but by repeating the treat-
ment the patient's life can be prolonged for months or
even years beyond the time when it would otherwise have
ended.

Although the effect of transfusion is apt to be transient
yet it is certain that its good effects are due not merely to
the addition of a certain number of healthy corpuscles to
the circulation, but, in addition, to an obscurer factor.
This can best be expressed by saying that the transfused
blood appears to have a stimulating effect upon the blood-
forming tissues of the patient, so that more red corpuscles
are discharged into the circulation. One observer believes
that enumeration of the reticulated red cells may be used
as an indication of the haemopoietic powers of the bone
marrow (289). The reticulated appearance is assumed to
be characteristic of cells which have recently entered the
circulation. The mode in which this stimulus acts is un-
known, and the whole subject calls for further investigation.
That this does take place is well illustrated by the following
details of three cases from Dr. Drysdale's wards at St.
Bartholomew's Hospital. The transfusions were given by
Dr. Joekes, who was also responsible for the estimations
of the corpuscles.

I. A woman, aged 51, had been treated for four years for

BLOOD DISEASES

53

pernicious anaemia, and when admitted to hospital was
becoming steadily worse. The red corpuscles numbered
1,470,000 per cmm., and her haemoglobin percentage was
32 on October 21, 1918, and by November 19 they had
fallen to 750,000 and 25. On November 22 she was trans-
fused with
500 CC. of
citra t ed
blood, and a
blood count
made imme-
diately after-
wards showed
that she then
had 1,410,000
red cells per
cmm. On
December 12
the number
had risen
to over
3,000,000,
and on Janu-
ary 2 8 of
the following
year it
was over
4,000,000.
This was still
maintained
in May, 1919,

and on the last occasion on which a blood count was made
she was found to have 4,400,000, with a haemoglobin
percentage of 90. Since then she has been lost sight of,
but would certainly have returned had she relapsed.
This case shows what remarkable results sometimes follow
a single transfusion and the progressive improvement

jK/d)'

^Kid"

3 X/O

2X.IO

'A^io'

-^

/

r

J

^

V

> '

\f

}

\

S lO

WEEKS

15

20

Fig. 3. — Pernicious Anemia, Case I

54

BLOOD TRANSFUSION

which follows the initial rise. The diagram shows the
results more graphically.

II. A similar result, even more striking, was obtained in
a woman aged 42. She was treated medicinally for four
months, during which time her red cells steadily decreased

froml, 250,000
to 429,000
per cmm .
She was then
transfused
with 400 cc.
of blood, and
her blood
count rose
immediately
to 967,000.
The rise con-
tinued steadi-
ly, and three
months later
her blood
count was
3,690,000 per
cmm. Two
very small ad-
ditional trans-
fusions were
given during
this period,
but to what
extent these

helped in the treatment cannot be estimated. The results
in this case also are represented graphically by the
diagram above.

III. A less favourable result is illustrated by the follow-
ing history : A stores assistant, aged 47, had been ill for
two years, and was first treated for pernicious anaemia in

5X/0

^-x-io

ay-io

2i</0

3 '/zx/o^

ii
1

B

1

1

S:

|/

1

< '

1

I

1

1

^

-

h^.

5 lO

15

20

25

<30

Fig. 4. — Pernicious Anemia, Case II

BLOOD DISEASES

55

April, 1920. He was medicinally treated with arsenic,
but no improvement followed. On June 18, 1920, his
corpuscles numbered 1,060,000 per cmm. He was trans-
fused with 600 cc. of blood, and his corpuscles increased at
once to 1,840,000 per cmm. A month later there had
been a further increase
to 2,520,000, but this
was not maintained, and
nine months afterwards
he was given a second
transfusion of 500 cc. of
blood. Immediately after
this his red cells num-
bered 1,800,000 per cmm.
(April 14, 1921). There
was a further slight rise
and then another rapid
fall, so that on June 4,
1921, he had only 830,000
red cells per cmm. He
was then given a third
transfusion of 700 cc.
The effect of this was a
steady rise, and on June
17 he had 2,112,000 red
cells per cmm. A fourth
transfusion of 500 cc. was
given at this point, and
thereafter the improve-
ment was maintained,
with slight variations,

until, on August 4, 1921, his corpuscles numbered 3,450,000
per cmm.

In this case the effect of the two first transfusions was
short-lived, but perseverance with the treatment brought
him in the course of two months from an extremely serious
condition to a state of comparatively good health, in which

5 i^lO^

4- Kit

3 KIO

ZXfcf

I X.IO

1''^

x/o

1.

1 !

1 ^

^1

/

A

/

H

r

vj

S lO

h/EEKS

15

20

Fig. 5. — Pebnicious Anemia, Case III

56 BLOOD TRANSFUSION

he could again for a time go about his business. The
diagram illustrates well the rise which followed each of the
later transfusions. He had again relapsed four months
later, but, unless each transfusion had chanced to coincide
with the remissions which may occur spontaneously in
this disease, it seems clear that the treatment greatly
relieved him for a time.

There is no objection to the use of citrated blood for
pernicious anaemia, so that the transfusion can be carried
out in the ordinary way described in Chapter VII. It is
necessary, however, to utter a warning as to the choice
of a blood donor. It is quite clear that in some patients,
whose disease has been diagnosed as pernicious anaemia,
there is an alteration in the reactions of the serum. The
corpuscles may show an agglutination which conforms to
one of the group tests described in Chapter VI ; never-
theless, it is essential in addition that the patient's serum
should be tested directly against the corpuscles of the
proposed donor, even if he belongs to Group IV, whose
corpuscles are not agglutinated by the serum of any normal
person. I was recently asked to transfuse a patient whose
disease had been diagnosed as pernicious anaemia. Her
red blood cells had fallen to 600,000 per cmm., so that she
was probably in the last stages. Her corpuscles were
agglutinated only by serum of Group III, so that she
apparently belonged to Group II. Only two donors were
available, both of whom belonged to Group IV. Never-
theless, the patient's serum strongly agglutinated the
corpuscles of both of them, so that I considered it inadvis-
able to carry out the treatment. Similar abnormalities
have been noticed by others. It seems to be a universal
experience that slight reactions are more commonly met
with after transfusion for pernicious anaemia than when it
is done for other conditions, although these do not in any
way prejudice the results that are obtained. These
reactions are possibly to be explained by abnormalities,
though of slight degree, in the patient's serum. In a case

BLOOD DISEASES 57

such as I have described the reaction would probably be
very severe, if not fatal. It is possible also that a well-
marked alteration in the serum reaction is not characteristic
of the clinical entity constituting true pernicious anaemia,
but in reality indicates that there is another underlying
cause for the anaemia, such as an undiagnosed carcinoma.
Dr. Joekes has recently (August 1921) told me that he
believes from his own observations that this is actually
the case, but it needs to be established by further investiga-
tion. The connexion between malignant disease and
abnormal serum reactions is referred to elsewhere
(p. 93).

Another possible complication is introduced into the
treatment by the necessity for giving repeated transfusions.
It has been noticed that sometimes a serious reaction
follows one or more of the later transfusions of a series,
even when the blood is taken from the same donor who had
been used before without ill effects. A report on several
such cases shows that this form of reaction cannot be
predicted or eliminated by the most careful testing before-
hand for reactions between the patient's serum and the
donor's corpuscles, though it has occasionally been so
severe as actually to hasten the patient's death (34). This
fact suggests that the reaction is not due to the presence of
agglutinins, but is rather of the nature of an anaphylactic
shock, the patient having been sensitized by a trace of
foreign protein introduced in the blood on the earlier
occasions. Possibly it may be to some extent avoided by
not using the same donor if another is available. It also
emphasizes the necessity for giving the blood slowly and
cautiously, so that the transfusion may be stopped at the
first sign of a reaction in the patient.

Very large numbers of transfusions for pernicious
anaemia have been given in the past, yet a reaction of a
dangerous severity has occurred in but few of them. This
need not, therefore, be regarded as a contra-indication for
transfusion, but rather as an indication for circumspection

58 BLOOD TRANSFUSION

in giving it. Transfusion is clearly a therapeutic measure
of great value.

Very recently it has been claimed by Waag that excellent
results have been obtained by the repeated subcutaneous
injection of small doses (5 cc.) of whole blood. In an actual
case which he reports, nine injections were given twice
weekly. If the claim be substantiated by further successes,
this method of treatment may eventually supplant the
more elaborate process of actual transfusion.

Toxemias
Bacterial Infections

Pyogenic. — The value of vaccines and bactericidal sera
in pyogenic infections, though not in universal favour, is
strongly advocated by many competent authorities, and
the transfusion of blood from an immunized donor suggests
itself as a natural corollary. A quantity of blood taken
from a vigorously reacting man and given to a debilitated
patient should theoretically supply him with a large amount
of the antibodies of which he stands in need. During the
war it was found that transfusion enabled an exsanguinated
patient better to withstand the attacks of pyogenic and
putrefactive organisms in his wounds, but this was probably
due to the improvement in the general circulation which
resulted rather than to any bactericidal properties in the
transfused blood. It is known that outside the body
blood has considerable powers of inhibiting the growth of
bacteria, but ordinarily it does not possess bactericidal
properties. It has been claimed, on the other hand, that
the best criterion of the degree of immunity in an
immunized animal is the measurement of the bactericidal
power of its blood. There is justification therefore for
attempting to combat a pyogenic infection by the trans-
fusion of immunized blood.

This method has at present not progressed beyond the
stage of preliminary trials. I have attempted it in one

TOXAEMIAS 59

case, but without any obvious benefit. The patient was
a middle-aged man suffering from a chronic staphylococcal
septicaemia and a secondary anaemia. He received a
transfusion of 650 cc. of blood from a donor who had himself
just recovered from a severe infection with staphylococcus
aureus. The patient's red blood cells miderwent a tem-
porary increase in number, but no other result was
observed. One series of nine cases has been recorded by
Fry, and in these the results leave some doubt as to the
efficacy of the treatment. Six of these patients were
almost hopelessly ill with streptococcal (five) or staphy-
lococcal (one) septicaemia, and only one of these responded
to treatment. He received transfusion from an ordinary
donor and two from immunized donors, who had been given
five or six injections of a mixed vaccine, the maximum dose
of which contained 120,000,000 streptococci. Improve-
ment definitely followed the transfusions, and his recovery
was afterwards encouraged by injections of an autogenous
vaccine. The other five patients received similar treat-
ment, but all died. The remaining three patients had
chronic suppuration, one following a streptococcal
arthritis of the knee, but no septicaemia, and all recovered.
It cannot be assumed that these recoveries were due to the
transfusions.

It is stated by Waugh that he transfused nineteen cases
of pyaemia of whom twelve recovered, and in these cases
an ordinary donor was used. No details, however, are
given, so that it is not possible to make any inferences from
this.

Greater success is claimed by Hooker, who reported that
in five cases of pyogenic infection the results were distinctly
favourable. He used immunized blood, but has formed
the impression that the transfusion even of normal blood
is of value in septicaemia by correcting the anaemia and
helping to restore the normal resistance. He recommends
that if the patient has a good blood volume and a high
bacterial content in the blood, he should be bled by

60 BLOOD TRANSFUSION

venesection before transfusion. A striking case of staphy-
lococcal septicaemia has been recorded by Little, who
believed that the patient's recovery was directly due to
the treatment. Four transfusions were given, the blood
for three of these being taken from donors who had each
received, four days previously, an injection of vaccine
made from the patient's own infection. Ottenberg and
Libmann have treated ten cases of pyogenic infections with
transfusions. All the patients were extremely ill and six
died. It is stated that the four who recovered " probably
owe their lives to the transfusion," but obviously it is
difficult to control the results. The same observers have
used transfusion in the treatment of infective endocarditis,
but unsuccessfully.

Some experimental work on this subject has been carried
out by Kahn. A bacterial infection was introduced into
the peritoneal cavities of several dogs. Continuous trans-
fusion between an infected dog and a healthy dog was then
performed, the blood passing to and fro between the
animals, sometimes for over an hour. It was found that
all the transfused animals fared better than those that
were not. The experiment suggests that resistance to
infection is heightened if two bodies can combat the in-
fection present in one ; but continuous transfusion is
scarcely practicable in man.

Diphtheria. — In the later stages of some acute diseases
due to a bacterial infection, the patient falls into a
condition of acute toxaemia, the symptoms of which
resemble in some ways those of shock. Harding has
drawn attention to this condition in diphtheria ; he has
produced it experimentally in animals and has treated it
by blood transfusion. The toxaemic stage was found to
occur on the fourth to the eleventh day. It was charac-
terized by a reduction of the output of the heart with a
corresponding fall in blood pressure, an exudation of lymph
into the tissues, and an increased specific gravity of the
blood. In all these respects it resembled the collapse due

TOXEMIAS

61

to trauma or to haemorrhage, and it was shown by experi-
ment that the treatment must be directed towards increas-
ing the amount of effective fluid in the circulation and to
decreasing its viscosity. It was found that normal saline
solution failed to do this ; gum-saline solution also failed,
and tended to produce a pronounced agglutination of the
red blood cells. Blood transfusion, on the other hand,
resulted in a considerable number of recoveries. In the
aggregate more than twice as many animals survived after
transfusion as survived without it, the same amount of
toxin being given in each case.

These experimental findings are exceedingly suggestive,
but the clinical efficacy of the treatment still remains to be
proved. Harding found that the amount of blood that
should be transfused was one-fifth of the total blood
volume ; the following amounts are, therefore, recom-
mended for the treatment of children in the toxaemia stage
of diphtheria :

Age.

Weight.

Amount.

U years .
2" „ .
4 „ . .
6 „ • .

21 lbs.
28 „
35 „
42 „

160 ccm.
200 „
300 „
400 „

Pneumonia. — A condition of toxaemia similar to that
seen in diphtheria was also observed in some of the cases
of pneumonia which complicated the influenza epidemic of
1918-19. In the United States, among a large number of
cases admitted to an emergency hospital, a series of 28
patients, some of whom were moribund, was treated by
blood transfusion by Rose and Hund. The results were
compared with those in 21 similar cases which were not
transfused. The figures seemed to show that transfusion
was of some value. Of the 28 who were transfused, 6, or
22-4 per cent., died, and the rest recovered ; of the 21 who

62 BLOOD TRANSFUSION

were not transfused, 9, or 47-7 per cent., died, and 12
recovered. The numbers treated are not large enough to
afford statistical evidence that can be relied upon, but the
results were at least encouraging.

Typhoid, Measles, Tuberculosis. — Transfusion has
been tried for several other bacterial infections with vary-
ing results. McClure has administered immunized blood
to a typhoid patient with a remarkably good result.
Ottenberg and Libmann have transfused five typhoid
patients, all of whom were desperately ill ; two of them
recovered. Transfusion has also been used for intestinal
haemorrhage in typhoid, but this is chiefly with the object
of combating anaemia. Subcutaneous injection of blood
has been successfully used by Terrien in a case of malignant
measles ; the donor had had measles six months previously.
Freilich has recently transfused six patients suffering from
tuberculosis, but without benefit. He is at present testing
the use of blood from donors who show a positive comple-
ment fixation test for the tubercle bacillus.

It is evident that treatment with immunized blood is
still in an experimental stage, but it merits further trials,
all the circumstances of which should be carefully recorded.
Toxaemias of Pregnancy. — The treatment of eclampsia
by blood transfusion was first employed by Kimpton, who
speaks favourably of the results obtained. Later it was
independently suggested to Blair Bell, who was the first
to employ it in this country, by certain investigations into
the facts of immunology. It had been found that symp-
toms resembling those of eclampsia could be produced in
mice by injecting into them an extract of placenta, whether
from a healthy or an eclamptic woman ; the same results
were obtained by injecting fresh serum from similar in-
dividuals. Further, if the placental extract was mixed
with serum from a normal person of either sex, the effects
were not obtained, and it was inferred that the placental
toxin had been neutralized by antibodies in the serum. If,
however, the placental extract was mixed with serum

TOXEMIAS 63

obtained from the blood of an eclamptic patient, then the
toxic symptoms were obtained as before. Apparently,
therefore, the serum in eclampsia lacks certain antibodies
which are present in the serum of normal individuals. If
these observations had been correctly interpreted, it seemed
reasonable to suppose that blood from a normal person
would supply an eclamptic patient with the antibodies
which she lacks. The patient treated by Blair Bell was
already comatose and apparently dying. She was given
500 cc. of citrated blood and rapidly recovered ; her
convalescence was uninterrupted. It would be unwise to
found great hopes on a single case, but the treatment
undoubtedly merits further trial.

Transfusion has also been used by Keator in treating the
toxaemia of early pregnancy, and Morel has successfully
used the blood of a healthy pregnant woman for the same
purpose. Gettler recommends the use of alkalinized blood
for " acidosis " in pregnancy. At present, however, little
evidence can be adduced in favour of this form of treat-
ment.

Nephritis. — ^A single case of nephritis successfully
treated by blood transfusion has been recorded by Ramsay.
The patient, a man aged 22, had been ill for ten days.
He was slightly drowsy and had a furred tongue. His
systolic blood pressure was 100 mm. and diastolic 60.
His urine had a specific gravity of 1010, and contained
much albumin and many granular casts, but no blood cells.
Vomiting was .incessant. On the second day after ad-
mission he passed 2 ozs. of urine and his systolic blood
pressure fell to 90 mm., his diastolic to 40 mm. His low
blood pressure and the evident imminence of suppression
of urine suggested the administration of blood ; he was
accordingly given 1,140 cc. of fresh blood. His blood
pressure immediately rose to 100 mm. systolic, and 50 mm.
diastolic, and the other symptoms abated. He passed
24 ozs. of urine during the ensuing twenty-four hours. He
was afterwards treated with alkalies, intravenously and

64 BLOOD TRANSFUSION

by the mouth, and his condition steadily improved. It
cannot be inferred from the evidence that his recovery is
to be attributed entirely to the transfusion, but it appears
to have been initiated by this treatment, which was a
reasonable one in view of the symptoms. No other similar
cases have as yet been recorded.

Carbon Monoxide Poisoning. — In any condition in
which the function of a large proportion of the red blood
cells as oxygen carriers has been temporarily destroyed or
impaired, it is a rational procedure to replace as many of
them as possible with normal red cells. The evidence
that transfused blood cells can carry out their functions in
their new host has been given on another page. In carbon
monoxide poisoning the oxyhaemoglobin has been converted
into carboxy haemoglobin, which is more stable than the
oxygen compound, and therefore useless for purposes of
respiratory exchange. Undoubtedly the ideal treatment
for carbon monoxide poisoning is by putting the patient in
a specially constructed chamber in which he can breathe
oxygen under a pressure of about three atmospheres. By
this means the carboxyhsemoglobin is dissociated and re-
placed by oxy haemoglobin. An oxygen chamber is usually
not available, though a very useful substitute may be tried
in the shape of a Haldane's oxygen mask. Failing this,
there is evidence to show that a blood transfusion is an
effective form of treatment. Nevertheless, although
poisoning with coal gas is by no means a rare event, this
treatment does not seem to have had the attention it
undoubtedly deserves. Transfusion was first used for
carbon monoxide poisoning by Hiiter in 1870, who was
able to record a case in which recovery appeared to have
been due to the treatment. It was also advocated by
Lauder B:unton in 1873. After this date recorded cases
are few, but in 1916 Burmeister put this form of treatment
on a more scientific basis by direct experiment. Using
rabbits and dogs he showed that if the animals treated with
coal gas were transfused without a venesection, 75 per cent.

TOXEMIAS 65

of them recovered. Of a series of control animals, which
were not transfused, nearly all died.

Most writers on the subject have recommended that as
much blood be taken from the patient by venesection as is
to be replaced by transfusion. On theoretical grounds this
seems to be sound, though it is not supported by the results
of Burmeister's experiments. Nevertheless, in a recent
series of seven cases reported by Bruce Robertson, in
which 1,000 cc. of blood were removed and the same amount
given by transfusion, satisfactory results were obtained.
If no venesection is done, there is some risk that the trans-
fusion may put an additional load upon an already over-
strained right heart, so that a preliminary venesection is
certainly a wise precaution. Transfusion should not be
withheld until the patient is in extremis ; if no oxygen
chamber is available, it should be given at once. A mini-
mum amount of 750 cc. of blood should be taken by vene-
section, and 1,000 cc. of blood should be given. If the
patient's condition does not then show enough improve-
ment, this should be repeated.

Nitrobenzol and Benzol Poisoning. — Blood trans-
fusion for poisoning with nitro-benzol (CgHgNOg) has been
recommended by Hindse-Nielsen, who records a case in
which it was successfully employed. The patient, a girl
of 19, had taken a tablespoonful of the poison several
hours before, and her condition appeared to be hopeless.
She was deeply cyanosed, the mucous membranes being of
a dark blue colour. Washing out the stomach and inhala-
tion of oxygen were tried without effect. Finally she was
bled to the extent of 600 cc, and 1,000 cc. of citrated blood
were injected. Her colour at once became more normal
and recovery followed. The literature does not contain
records of any other cases treated in this way, but the
condition is analogous to coal-gas poisoning referred to in
the last paragraph, oxyhsemoglobin being in this case
replaced by methhsemoglobin, and its treatment by trans-
fusion has, therefore, a rational basis.
5

66 BLOOD TRANSFUSION

A somewhat similar condition is seen in benzol poisoning,
though there is an additional destruction of red blood cells.
Three cases treated by transfusion have been reported by
McClure. One patient, whose red blood cells had been
reduced to 1,460,000 per cmm., was extremely ill, but
recovered after five transfusions up to a total amount of
1,500 cc.

Diabetes. — Blood transfusion has been used in treating
diabetes mellitus, but there is no evidence to show that it
is of any service. Ottenberg and Libmann transfused four
patients who were already in diabetic coma, but no
improvement resulted. Another patient who was trans-
fused by Raulston was actually made worse, as was
indicated by an increased output of sugar, acetone, and
ammonia compounds.

Pellagra. — The precise aetiology of pellagra being still
unknown, treatment of the disease can only be empirical.
From this point of view blood transfusion has been tried
by Cole, who began using it in 1908. The results in twenty
cases have been reported, and are distinctly encouraging.
All the transfused patients were in the last stages of the
disease, but nevertheless a recovery rate of 60 per cent,
was obtained, the usual rate being 10 to 20 per cent. In
the present state of knowledge comment is scarcely possible,
but if pellagra is, as some observers have suggested, a
" deficiency disease," it may be supposed that the trans-
fused blood provides a temporary supply of the substance
that is lacking ; the patient is thus enabled to start along
the road to recovery.

CHAPTER IV

DANGERS OF BLOOD TRANSFUSION

Appreciation of the dangers attending the practice of
blood transfusion has varied greatly at different times.
In the seventeenth century a happy ignorance took no
account of them whatever. In the eighteenth century
they were so greatly feared that transfusion fell into
abeyance. In the nineteenth century it was realized that
dangers existed, but they were imperfectly understood ;
when fatalities occurred, a partial knowledge explained
them away more easily than our fuller knowledge can
to-day, so that transfusion was practised in spite of them.
At the beginning of the twentieth century, with the dis-
covery of " blood groups," it was thought that all danger
had been eliminated. At the present time the pendulum
is swinging back again, and the problem of the complete
elimination of danger is proving more complex than it was
thought to be a few years ago.

The chief dangers of blood transfusion are two -fold —
that of introducing into the recipient a disease carried by
the donor, and that due to the inherent properties of the
donor's blood which may interact in a serious manner with
the blood of the recipient. The first of these dangers is
obvious, and common sense will suggest what steps should
be taken to avoid it. Danger of communicating disease is
almost restricted to conditions in which an infective agent
is actually circulating in some form in the blood. Inquiry
will usually be enough to establish the possible presence
in the prospective donor's blood of an organism such as the
malaria parasite. Nevertheless, a case has been recorded

67

68 BLOOD TRANSFUSION

by van Dijk, in which malaria was transmitted by injecting
into a patient suffering from influenza some serum obtained
from another patient who was supposed to be convalescent
from influenza, but had been treated for malaria a few
months earlier. Another case is reported by Bernheim,
who transmitted a double infection of malaria — tertian and
sestivo -autumnal — by means of a blood transfusion. Blood
infections, such as those due to the exanthemata, may be
avoided by the precaution of never employing a blood donor
who shows any signs of present illness, even though a
raised temperature be the only symptom. In certain cases,
when, for instance, the prospective donor may be suffering
from tuberculosis in some form or from gonorrhoea, the
organism is extremely unlikely to be present in the blood in
numbers sufficient to communicate disease. Nevertheless,
on general principles, such donors should be eliminated if
circumstances permit. The most subtle form of infection,
the most dangerous, and the most difficult to eliminate, is
syphilis. Definite cases have been recorded in which
syphilis has been communicated by blood transfusion. In
one instance recorded by Sydenstricker and by Bernheim
a father was infected by blood taken from his son, who
had refused beforehand to allow himself to be tested.
Fortunately such occurrences are rare. Still rarer and still
more curious is the transmission of horse asthma recorded
by Ramirez. In this instance, in which the disease is to
be regarded as a form of anaphylaxis, the patient had
received an amount of serum sensitive to horse protein
great enough to provide him with the corresponding
symptoms for some time afterwards.

If the transfusion is being done at leisure, the donor's
blood must be tested for a positive Wassermann reaction.
Even this test, however, has been known to fail, and since,
in an emergency, the most careful inquiry, aided by a
desire on the part of the donor to arrive at the truth, may
reach an erroneous conclusion, the risk of infection with
syphilis can never be completely eliminated. Since

DANGERS OF BLOOD TRANSFUSION 69

reasonable care can make the danger a remote one, it need
not hinder the performance of a transfusion any more
than an occasional death under anaesthesia prevents the
frequent use of general anaesthetics. The mere existence
of such a danger is, however, an argument in favour of the
general use of the " professional blood donor," whose
Wassermann reaction, personal history, and mode of life
are well known to the practitioner ; the previous use of his
blood on perhaps more than one occasion, if unattended by
any ill results, will give an added confidence. The tragedy
of such a misfortune is so great that no precaution which
can possibly be taken should be regarded as absurd.

The second danger present in the inherent qualities of
the donor's blood has been already alluded to in the
historical sketch of the subject. Before the existence
of the " blood groups " was realized, a number of fatalities
due to an unexplained cause had occurred. Even after
the existence of the groups had been demonstrated, the
warning that resulted was apt to be disregarded, and it
was not until still further fatalities due to this incompati-
bility of bloods had taken place that the very important
nature of the discovery came to be understood. The
chances are, on the whole, that the blood of any donor
chosen at random will not prove fatal to a given recipient ;
nevertheless, it must frequently happen that the transfusion
without being fatal will be wasted, or to some degree
detrimental. It is therefore evident that the existence of
blood groups must be seriously regarded, and it is necessary
to enter into a detailed consideration of their relations to
one another and the symptoms which they may produce.
In the next chapters will be found a further description of
their physiology and pathology and of the methods of test-
ing for them.

It has long been known that if the blood of one species
of animal is injected into the circulation of another species,
the corpuscles of the foreign blood are at once destroyed,
their contained haemoglobiu being set free. This process

70 BLOOD TRANSFUSION

of haemolysis is under such circumstances rapid and
complete, and haemoglobin may appear in the urine in a
short time. The precise nature of the reaction is obscure
and need not be discussed here in detail. The present
bearing of the phenomenon is the fact that a similar, or
analogous, reaction may occur when the bloods of certain
individuals are mixed with the bloods of certain others
even of the same species. It was the observation of this
fact that first led to the discovery of the so-called " blood
groups " among human beings, and so to the partial
elucidation of the cause of the previously unexplained
fatalities following blood transfusion. In 1901 Landsteiner
had detected the presence of hsemolysins and iso-haemoly-
sins in blood and classified three groups in human beings.
In 1907 it was shown by Jansky that human beings may
be divided into four groups, the blood of the members of
each group having a certain definite relation to the blood
of the other groups as determined by the manner of their
interaction. The work was repeated and confirmed by
Moss in 1910. The reaction takes place between the
serum of one group and the corpuscles of the other groups,
and is evidenced by the agglutination or haemolysis of the
corpuscles that are being acted upon. In the course of
his researches Moss showed that haemolysis, or the breaking
up of the corpuscles, is always preceded by agglutination
or the clumping together of the corpuscles. The process
does not necessat'ily go as far as the destruction of the cor-
puscles, but may be arrested at the stage of agglutination.
It may, on the other hand, be as rapid and complete as if the
bloods belonged to different species, and the appearance of
haemoglobin in the urine may quickly give evidence of this.
The groups have been arbitrarily numbered, and it is
now usual to refer to them by the Roman numerals I, II,
III, and IV. According to the accepted convention, the
reactions of these four groups are as follows : ^

1 The notation used here is that initiated by Moss in 1910. This does
not agree with the notation introduced three years previously by Jansky,

DANGERS OF BLOOD TRANSFUSION 71

The corpuscles of Group I are agglutinated by the sera
of II, III, IV. The corpuscles of Group II are agglutinated
by the sera of III, IV. The corpuscles of Group III are
agglutinated by the sera of II, IV. The corpuscles of
Group IV are not agglutinated by any of the other groups.

On the other hand :

The- serum of Group I agglutinates no other corpuscles.
The serum of Group II agglutinates the corpuscles of
Groups I, III. The sertim of Group III agglutinates the
corpuscles of Groups I, II. The serum of Group IV
agglutinates the corpuscles of Groups I, II, III.

This may be represented -more graphically by the follow-
ing table, a -f indicating agglutination, a — indicating
no reaction :

Serum

I

n -

III

IV .

CO

©

8

I ^

-

-f

+

+

II

-

-

+

+

III '

-

+

-

+ -

IV

-

-

-

The active principle in the serum is called " agglutinin "
or " hsemolysin," according to the degree of the reaction,
and the corpuscles are rendered sensitive to this by the

the Groups I and II of Moss corresponding to the Groups IV and III of
Jansky and vice versa. The difference has given rise to confusion and some
disasters, and it has been recently recommended by an American Medical
Committee that the notation of Jansky be universally adopted on grounds
of priority. This decision is no doubt fully justified in American practice,
but in this country the notation of Moss has been so generally used that I
have not attempted to reverse it. The possible dangers that may arise
should, however, be realized.

72 BLOOD TRANSFUSION

possession of an " iso-agglutinin " or " iso-hsemolysin."
Sometimes the corpuscles are said to have " agglutino-
philic " properties. It may be stated, therefore, that the
serum of Group I entirely lacks agglutinins, whereas the
corpuscles of Group IV lack iso-agglutinins. All these
terms, like the " amboceptors," " receptors," and " hapto-
phores " of Ehrlich, are used to conceal ignorance rather
than as an expression of knowledge, but, until more light
has been shed upon the nature of the reactions, ignorance
must be abbreviated.

It is now clear that the blood as a whole contains two sets
of reactions which are independent. These properties
reside in the serum and in the corpuscles respectively, and
the reactions are complementary between Groups II and
III, that is to say, the serum of each group agglutinates
the corpuscles of the other. It will be seen from the table
that the serum of Group I blood does not agglutinate the
corpuscles of any of the other groups, and conversely the
corpuscles of Group IV are not agglutinated by the serum of
any of the other groups. Individuals of Groups I and IV
have therefore been named " universal recipients " and
" universal donors "respectively. This implies that if the
recipient be found to belong to Group I, the blood of any
donor may be transfused into his veins irrespective of his
group, and that if the donor be of Group IV, his blood may
be used for transfusion irrespective of the group of the
recipient. These statements may be accepted as true in
an emergency, but important reservations may have to be
made under certain conditions.

It was at one time believed that the group reactions were
clear-cut and absolute rather than relative. At the
present time, however, the view is gaining ground that
there may be some " over-lapping " of groups, that is to
say, a serum may contain agglutinins which give a gross
reaction with the corpuscles of one group and a reaction
with another group so slight that it can be detected only
with difficulty, or alternatively the recipient's corpuscles

DANGERS OF BLOOD TRANSFUSION 73

may give a definite and limited group reaction, while his
serum may cause some agglutination in the blood of a
theoretically compatible group. These properties have
recently been termed " major " and " minor agglutinins "
by Unger, who claims that the possible presence of minor
agglutinins makes it advisable to test the recipient's blood
directly against the donor's in every case. The term
" universal donor " commonly applied to Group IV is, in
fact, misleading. The blood of Group IV cannot be used
indiscriminately with complete impunity. The groups are
determined by the major agglutinins, and by these the
ordinary gross reactions may be eliminated. Everyone
who has used blood transfusions extensively has observed
that slight reactions may occur after transfusion with a
compatible blood, irrespective of the methods employed.
Usually these reactions are slight, and do not in any way
prejudice the benefits conferred by the transfusion, but
they may become greatly accentuated in the later trans-
fusions of a series, and it is probable that minor agglutinins
may be developed in certain pathological conditions.
Further reference to these phenomena will be made else-
where (p. 93). In addition to this, it has been commonly
observed that the intensity of the reaction varies greatly
with the sera of different individuals of the same group.
It has also been stated by Stansfeld that the agglutinating
power of the serum of an individual may vary from time
to time. As a rule the corpuscles of a person belonging
to Group I are not agglutinated with equal rapidity
or intensity by the sera of Groups II and III, but
the meaning of this phenomenon has not been fully
investigated.

A possible source of trouble will occur to anyone looking
critically at the table of reactions, for it will be noticed
that the serum of Group IV, the so-called " universal
donors," agglutinates the corpuscles of all the other groups.
How does it come about, therefore, that the blood of this
group may be given indiscriminately ? The answer is to be

74 BLOOD TRANSFUSION

found in the fact that though the reaction takes place as
shown in the table outside the body, nevertheless the serum
of the transfused blood does not exert its agglutinating
power in the body of the recipient. Several hypotheses
have been advanced to account for this discrepancy, though
no final explanation has yet been arrived at. In the first
place it is possible that the agglutinating power of the serum
is rendered ineffective by the dilution which it undergoes
when it is mixed with the blood of the recipient. It has
been shown, however, by Culpepper that agglutination
takes place outside the body with serum diluted up to
1 : 150, a degree of dilution far greater than is ever obtained
in a transfusion where the dilution in the patient's circula-
tion is usually no greater than 1 : 7. Secondly, it has been
suggested that the transfused plasma meets with an excess
of plasma containing protective or antihsemolytic pro-
perties. The evidence on this point is conflicting. Hek-
toen in 1907 was unable to demonstrate any such property
in serum or plasma. Brem and Minot in 1916 both claimed
to have demonstrated antihaemolytic properties in serum,
and Minot added the observation that its concentration
varies. Karsner in 1921 reported that he had failed to
demonstrate anti-agglutinins in the blood. For the present,
therefore, the point must remain undecided. Finally, it is
possible that the agglutinins of the transfused plasma,
meeting with an excess of agglutinable cells, are all absorbed
without actually producing any agglutination. Which-
ever of these hypotheses be true, the fact remains that the
blood of Group IV individuals may be given without
serious effects in most ordinary cases in which transfusion
is indicated.

It must not be inferred from the tabulated reactions that
a transfusion with the blood of an incompatible group
necessarily produces a fatal, or even a serious, result. If,
for instance, an individual of Group II be transfused with
blood of Group III, the corpuscles of the donor's blood will
certainly be rendered ineffective, being destroyed either at

DANGERS OF BLOOD TRANSFUSION 75

once or in the course of a short time. But beyond this
wastage of the transfused blood there may be no effects,
as shown by morbid symptoms in the recipient ; he will
merely not be benefited. There may, on the other hand,
be an evident reaction in the recipient, the symptoms
varying from slight discomfort to almost immediate death.
It appears, therefore, that there is a gradation of toxicity
between the bloods of incompatible groups, so that it may
be justifiable owing to extreme urgency in certain cases to
perform a transfusion without doing any preliminary tests
on the bloods of donor and recipient. There is a good
chance that the groups will be compatible ; if, however,
they be incompatible, there is still a good chance that the
recipient will be no worse off than he was before the
transfusion.

Even when the tests have been performed, it may still
happen that through various causes a mistake has arisen.
Owing to the inexperience of the operator or to staleness of
the sera used in performing the test, an incompatible group
may appear to be compatible. It is necessary, therefore,
that everyone who performs a transfusion should be able
to recognize the symptoms of a reaction as soon as it begins
to appear, so that the transfusion may be at once discon-
tinued. Sometimes the reaction between incompatible
groups is so immediate and severe that death takes place
almost at once. I did not myself perform any transfusions
until after the period when blood-grouping tests had
become a routine procedure, so that I have no personal
experience of such unfortunate results. The symptoms
may therefore best be described in the words of one who
has several times witnessed the effects of an incompatible
blood : " The clinical picture of these reactions is typical.
They occur early, after the introduction of 50 cc. or 100 cc.
of blood ; the patient first complains of tingling pains
shooting over the body, a fullness in the head, an oppressive
feeling about the precordium, and, later, excruciating pain
localized in the lumbar region. Slowly but perceptibly

76 BLOOD TRANSFUSION

the face becomes suffused a dark red to a cyanotic hue ;
respirations become somewhat laboured, and the pulse
rate, at first slow, sometimes suddenly drops as many as
from twenty to thirty beats a minute. The patient may
lose consciousness for a few minutes. In one-half of our
cases an urticarial eruption, generalized over the body, or
limited to the face, appeared with these symptoms. Later
the pulse may become very rapid and thready ; the skin
becomes cold and clammy, and the patient's condition is
indeed grave. In from fifteen minutes to an hour a chill
occurs, followed by high fever, a temperature of 103° to
105°, and the patient may become delirious. Jaundice
may appear later. The macroscopic appearance of
hgemoglobinuria is almost constant." (Peterson.)

In a fatal case recorded by other writers the chief
symptom was hsemoglobinuria, which progressively in-
creased until the functions of the kidney became so much
interfered with by deposits of haemoglobin or damaged
corpuscles that the patient died with suppression of urine
and all the signs of uraemia (25).

In other cases a slighter and transient hsemoglobinuria
has been noticed, showing that some destruction of red
cells has taken place without producing any further effects.
This symptom is, of course, due to haemolysis following
reactions between the serum and corpuscles as explained
above. The variation in degree of the reaction is to be
partly explained by the fact that there are three possibili-
ties : (1) The donor's corpuscles may be haemolysed by
the recipient's serum ; this will result in the transient
haemoglobinuria and wastage of the transfused blood ; (2)
the recipient's corpuscles may be haemolysed by the donor's
serum, or (3) serum of each may haemolyse the other's
corpuscles. Either of the latter events will be extremely
serious. As already mentioned, haemolysis is always pre-
ceded by agglutination, and it seems that the agglutination
may be the more rapidly fatal of the two. It was probably
this that was chiefly responsible for the suppression of urine

DANGERS OF BLOOD TRANSFUSION 77

in the case referred to, and a case has been recorded in
which it appeared to be the only cause of immediate death
or, as an American writer expresses it, " sudden exitus took
out, out of a clear sky," owing to the presence of multiple
emboli.

In addition to the evidence of haemolysis the patient
may exhibit the symptoms described above. Sometimes
the urticarial rash has been accompanied by vomiting and
headache. This group of symptoms suggests that the
condition is analogous to the anaphylactic shock which
may follow the intravenous injection of any foreign protein.
The symptoms in a mild degree do occasionally follow the
transfusion of blood which has been shown to belong to a
compatible group, and it had been foimd to develop even
to an alarming extent after the later transfusions, when a
series was being given for a condition such as pernicious
anaemia (34). In such cases, however, as is suggested else-
where, this may, perhaps, be regarded as true anaphylactic
shock. The symptoms which may accompany a first
transfusion cannot be identical with this since true anaphy-
laxis must have been preceded by sensitization with a
minimal dose of foreign protein introduced into the circu-
lation.

It was formerly thought that possibly the products of
haemolysis were themselves toxic and capable of producing
the symptoms described. This seems, however, to have
been disproved by Bayliss, who has shown that in the dog
and cat the haemolysed blood of the same species is, with
extremely rare exceptions, innocuous.

Another possible cause of similar symptoms is the sodium
citrate used as an anticoagulant in one of the methods
of transfusion subsequently to be described. But the
symptoms, if due to this cause, will not be accompanied by
any signs of haemolysis, are usually not severe, and are
always very transient. This will be referred to again
later on.

The symptoms of incompatibility begin to be apparent

78 BLOOD TRANSFUSION

so quickly that the worst results can be avoided by the
exercise of caution. If for any reason it has been
necessary to use an untested blood donor, the first 100 cc.
of blood should be injected very slowly. If no untoward
symptoms result, the remainder of the blood can be
injected with greater confidence. Little can be said as to
the treatment of this condition, for prevention is far better
than cure. When the symptoms have developed, the
damage has been done, and cannot be imdone. The ordin-
ary measures for combating severe collapse may be used.

A lesser danger of transfusion is that of administering
the blood too rapidly. Sometimes during a transfusion
the patient complains of difficulty in breathing and a
sensation of tightness in the chest ; this should always be
regarded as a warning that the blood must be given more
slowly or perhaps that enough has been given and that the
transfusion should be discontinued. Usually the symptom
amounts to nothing more than disconlfort, and will dis-
appear if caution be exercised. The explanation is to be
found in the too rapid filling of the venous side of an im-
paired circulation with overloading, and perhaps temporary
dilatation, of the right side of the heart. I have never seen
these symptoms occur to an alarming degree, but actual
loss of consciousness with a very rapid and feeble pulse
has been recorded by other writers. Directions as to the
amount of blood which should be given and the rate at
which it should be injected so that these symptoms may
be avoided will be found under the description of methods
given in a later chapter.

CHAPTER V

PHYSIOLOGY AND PATHOLOGY OF BLOOD GROUPS

In the foregoing chapter the reactions between the blood
groups and the morbid symptoms which may follow the
injection of incompatible blood have been described. In
the present chapter some account will be given of the more
general physiology and pathology of the groups.

It seems to be clear that iso -agglutinins and iso-haemoly-
sins, that is to say, serum reactions among the individuals
of a species, are to be found distributed widely through the
animal kingdom. The phenomenon is, however, weak in
operation compared with that found among human beings,
and it is very much more difficult to demonstrate. The
facts have not been investigated for very many species of
animals.

Some of the earliest attempts to investigate the distribu-
tion of iso -agglutinins among animals were made by Hek-
toen in 1907. He tested the blood of rabbits, guinea-pigs,
dogs, horses, and cattle ; his results were negative in every
case, but probably his technique was imperfect or an in-
sufficient number of animals was tested. Grouping has
been found among goats by Ehrlich. Ottenberg and others
believe that they have demonstrated the existence of three
groups among steers, and of four groups among rabbits.
Von Dungernhas shown that there are four groups among
dogs. Agglutination reactions were found by Ingebrigtsen
and by Ottenberg among cats, but they were not constant,
and it was not found possible to distinguish any grouping.
The same was found to be true of rats. I have not been
able to discover any record of research upon iso -agglutinins

79

80 BLOOD TRANSFUSION

in birds or reptiles. The phenomenon of blood groups has
a possible bearing on the success or failure of experimental
transplantations of tissue, whether healthy or diseased,
from one animal to another of the same species. From
this point of view an investigation of the blood reactions
among mice was carried out by B. R. G. Russell in the
laboratories of the Imperial Cancer Research Fund, but he
was unable to find any sort of grouping. Ingebrigtsen has
made an attempt to correlate the results of the transplanta-
tion of arteries in cats with their serum reactions, but he
was unable to do so. His results were equally bad whether
iso-agglutinins were present or not. Nevertheless, it is
highly probable that the success of tissue transplantation
in man will be found to be largely dependent upon com-
patibility of blood groups in donor and recipient. The
problem is one that cannot easily be investigated by experi-
ment on animals, among which natural incompatibility is
evidently much less well marked than it is in man. A
method of overcoming this unsuitability is suggested by
the experiments of Ottenberg and Thalimer. These
observers, as already mentioned, found that in cats iso-
agglutinins were present, though inconstant ; on the other
hand, iso-haemolysins were seldom if ever found in normal
cats, though they often appeared in the recipients of trans-
fusions. Grafting experiments might therefore be preceded
by transfusions designed to stimulate artificially incom-
patibility of the tissue fluids.

The incompatibility of blood is essentially a phenomenon
which distinguishes different species of animals, since in no
case can the blood of one species circulate unaltered in the
blood-vessels of another kind of animal. This serological
specificity may be in some way related to the sterility of
one kind of animal with another, though not actually
causing it, and so be merely an incidental phenomenon.
It cannot be in any sense protective, since it never happens
in the course of nature that blood is transferred from one
animal to another. In the same way it is difficult to see

PHYSIOLOGY OF BLOOD GROUPS 81

how there can be any biological " purpose " in similar
differences between individuals of the same species, and,
so far as is at present known, the possession of a particular
group does not confer upon its owner any advantage over
the individuals of other groups, such as a relatively greater
immunity from disease, longevity, or fertility. It is quite
clear that there is no connexion between incompatible
blood groups and sterility between individuals.

An investigation of a possible relation between blood
groups and disease has been begun by W. Alexander at St.
Andrews University. In a preliminary communication
concerning the blood groups found among fifty patients
suffering from " malignant disease " of all forms, including
leukaemia, he has found that there is a considerably higher
proportion of Groups I and III than among healthy people.
On the other hand, the groups are found in the normal
proportions among people suffering from tuberculosis,
syphilis, and tetanus. It would, however, be premature
to assume that individuals of Groups I and III are more
liable to suffer from " malignant disease " than other
people, as the numbers tested are, at present, too small for
definite conclusions to be formulated. Also it remains to
be proved that the presence of malignant disease does not
produce an alteration in the agglutinating reactions by
which the groups are determined.

It seems probable that the differences between the groups
have arisen incidentally in the evolution of mankind,
possibly as the result of the parallel descent of two or
more original stocks from different sources, which after-
wards converged and mingled, with the production of
serological hybrids. In view of this it ic of interest to find
that some investigation of the racial incidence of blood
groups has already been carried out. On the Macedonian
front during the war a large number of men of many
different races were gathered together, and scientific
advantage of this opportunity was taken by L. and H.
Hirschfeld. The blood groups were determined in
C

82 BLOOD TRANSFUSION

approximately 8,000 individuals, including French, Eng-
lish, Italians, Germans, Austrians, Serbs, Greeks, Bul-
garians, Arabs, Turks, Russians, Jews, Malagasies, Senegal
Negroes, Annamese, and Indians. According to the
results obtained by the Hirschfelds, the groups designated
II and III show a definite variation in their distribution
among different races. As will be seen hereafter. Group I
is compounded of the two factors producing Groups II
and III, while Group IV results from their absence. It is
therefore necessary only to consider the incidence of
Groups II and III in calculating the racial differences. For
the statistical tables and diagrams the reader must be
referred to the original paper published in 1919, but the
results may be roughly summarized as follows. It was
found that the factor producing Group II is prevalent
among European peoples, whereas the factor producing
Group III is characteristic of men from Asia and Africa.
Thus the Group II factor was found in not less than 45
per cent, among most European peoples. It gradually
diminishes in the countries lying between Asia and Central
Europe, being present in Arabs 37 per cent., in Russians
37 per cent., in Jews 38 per cent. In Asiatics and Africans
it falls considerably, being in Malagasies 30 per cent., in
Negroes 27 per cent., in Annamese 29 per cent., in Indians
27 per cent. On the other hand, the factor producing
Group III shows exactly the opposite variation. Among
the English, the most Western people of Europe, it is rare,
being found by these observers to be present in only 10
per cent. ; it rises to 14 per cent, in French and Italians,
to 18 per cent, in German Austrians, and to 20 per cent, in
the Balkan peoples. In Africa and Asia the Group III
factor rises considerably, being present in Malagasies 28
per cent., in Negroes 34 per cent., in Annamese 35 per
cent., and in Indians 49 per cent.

We may still be far from elucidating the anthropological
meaning of these facts, for the mingling of the hypothetical
stocks of which mankind is made no doubt began in a

PHYSIOLOGY OF BLOOD GROUPS

83

remote antiquity, and it is possible that a serologically pure
race does not exist. The investigation, however, of the
more isolated peoples might throw much light on the
problems of anthropology.

Interesting as the wider questions may be, we are here
more immediately concerned with the distribution of the
blood groups amongst our own population. The percen-
tages in which the four groups occur have been estimated
by various observers, and, as will be readily understood
from the foregoing remarks, the numbers show some
variation. The approximate figures as worked out by
three observers in America are as follows :

Bernheim

Moss

Culpepper

(1,600 tests)

(5,000 tests)

I

2

10

3 per cent.

II

40

40

38 „ „

III

15

7

18 „ „

IV

43

43

41 „ „

The percentages found among the first hundred men
whom I tested in the British Army in 1917 conformed
almost exactly to the first of these series of figures, and
they may be taken as an average result for Western peoples.
It will now be seen upon what grounds it was stated in the
last chapter that the chances were in favour of the blood
of a donor chosen at random being compatible with that
of the recipient. If the patient belong to Group II, then
83 per cent, of other bloods will be compatible. If he
belong to Group III, 58 per cent, will be compatible. Only
if he belong to Group IV will the chance in favour of com-
patibility fall below 50 per cent.

This statement of the facts concerning distribution of
the blood groups will serve to emphasize the absolute
necessity for the careful testing of a donor before his blood
is used for transfusion. But, further than this, it is
necessary to clear away several widely spread misappre-

84 BLOOD TRANSFUSION

hensions as to the group relations between an infant and
its mother and between the various members of a family.
It has several times been stated in print that a mother's
blood must be compatible with that of her child, or some-
times that a baby has no blood group, so that it may be
safely transfused with blood taken from its mother or its
father without preliminary testing. On other occasions
the statement has been made that the brother or sister of
a patient is more likely than other people to belong to the
same or a compatible blood group, so that imtested blood
may be transfused from one member of a family to another
with little risk. Knowledge of the existence of blood
groups has become somehow mixed up with vague popular
beliefs concerning " affinities " and " blood relations."
Such confusions must, however, be dissipated, for none of
these statements are more than partially true, and they
may lead to a false sense of security and to disaster.

The assertion that an infant has no blood group was
tested by the writer some time ago and shown to be false.
On several occasions a newly born infant was tested and
found to show well-marked agglutination reactions in-
dicating Groups II or III as the case might be. Even in
1905 it had been shown by Martin that reactions could
often be demonstrated between an infant's corpuscles and
the maternal serum, and sometimes between the infant's
serum and the maternal corpuscles. More recently (March
1920) the results of a full investigation into the reactions
found in infants and children have been published by W. M.
Happ in America. These researches began with the testing
of blood from the umbilical cord, and this was seldom found
to show the blood reactions as given by the adult. So far
the statement quoted above was justified. It is even true
that the serum of an infant's blood will usually not give any
reaction at birth or during the first month. The percen-
tage in which it does give a reaction increases with the age
of the child ; after one year it is usually, and after two years
always, established. On the other hand, the agglutination

PHYSIOLOGY OF BLOOD GROUPS 85

reaction in the corpuscles appears before that in the serum,
so that the grouping tested in this way may be present
immediately after birth, as I found to be the case. It is
possible that the grouping which first appears may after-
wards be modified, but any change which occurs is always
by the addition of factors and not by their subtraction ;
thus an apparent Group IV may become a Group II or III,
or an apparent Group II or III may become a Group I.
It is found that when a reaction is present in both the
corpuscles and the serum, the group does not afterwards
change. Happ's conclusion, based on his investigations,
was that it is unsafe to transfuse an infant with its mother's
blood without first making the usual tests, and the reasons
for this will now be evident. In the first place an infant
may be possessed of its final blood reactions very shortly
after birth, and should therefore be treated in the same way
as if it were an adult. In the second place, although its
serum may be without agglutinating powers, so that
transfused corpuscles will not be attacked, yet its corpuscles
may be possessed of pronounced agglutinophilic properties,
so that they may be seriously affected by the serum of
transfused blood from an incompatible group. In the
third place, as will presently be seen, it is by no means the
rule that an infant should belong to the same group as its
mother, whatever its blood reactions may be.

Another set of observations, leading to precisely the
same conclusions, have been made by F. B. Chavasse of
Liverpool. He terms the potential agglutination of the
foetal corpuscles by the mother's serum, and of the maternal
corpuscles by the serum of the foetus, the " maternal
threat " and the " foetal threat " respectively, and states
that there is no obvious relationship between the " foetal
threat " and eclampsia or the toxaemias of pregnancy.
The inference is therefore justified that there is no trans-
ference of the agglutinating substances in either direction
across the placental membranes. No chemical "im-
munity " is acquired, therefore, on either side, since the

86 BLOOD TRANSFUSION

protection is mechanical. This agrees with the fact ob-
served by Happ that the mother's milk contains the same
agglutinins as the serum of her blood ; but these do not
have any deleterious effect upon the infant, and are there-
fore either not absorbed at all or are destroyed in the
process of digestion.

The statement that the blood group of an infant is not
necessarily the same as that ot its mother can be amplified,
for it has been found that blood groups are inherited on a
definite plan, so that if the groups of the parents be known,
certain predictions can be made as to the possible groups
that may be found among their offspring. Many characters
in animals and plants have been shown during the last
twenty years to be transmitted according to the Mendelian
plan of inheritance, but up to the present time very few
normal characters in man have been isolated, and their
manner of inheritance demonstrated, though a number of
pathological conditions have been shown to conform to the
theory. It is therefore of much interest to find that the
inheritance of blood groups in man can be quite satisfac-
torily and consistently explained in Mendelian terms.

According to this theory, each quality in an organism
which can be isolated and investigated independently of
other qualities, is termed a "unit character," and the
appearance of each such unit character is determined by
the presence of something called a " factor " in the sexual
cells or " gametes," male and female, by the union of which
the individual is formed. Further, these unit characters are
believed to occur in alternative pairs, and at first it was
supposed that each alternative pair consisted of " domi-
nant " and " recessive " characters, the second of which
could only make its presence apparent in the individual
if the dominant character were absent. Subsequently it
was seen that the dominant and recessive characters need
not necessarily consist of two positive, though opposite,
qualities, but might better be regarded as consisting of the
presence of a character and its absence. To use a classical

r

PHYSIOLOGY OF BLOOD GROUPS 87

illustration of this view, sweet peas may be classified into
tall peas and dwarf peas. At first the unit characters were
taken to be tallness (dominant) and dwarfness (recessive).
Later this idea was modified, and it was said that
potentially all peas are dwarf, but to some is added a
factor producing tallness, this factor being absent in those
that are dwarf. To represent this idea more simply a con-
ventional notation has been used, according to which the
large letters of the alphabet indicate the presence, and the
small letters the absence, of each factor.

In order to apply this theory to the case under considera-
tion, it has been suggested that two pairs of factors are
concerned :

A the presence of the character producing Group II.
a the absence of the character producing Group II.
B the presence of the character producing Group III.
b the absence of the character producing Group III.

Each pair of factors is transmitted independently of the
other. Both A and B may be absent, in which case the
individual belongs to Group IV ; or both may be present,
and in this case the individual gives the reactions of
Group I.

It must be understood that the term " character pro-
ducing Group II " is here used as a convenient way of
expressing the obscure and probably complicated set of
properties responsible for the reactions manifested by in-
dividuals of Group II. It includes not only the agglutinin
or haemolysin of the serum which reacts with corpuscles of
Group III, but also the complementary iso -agglutinin or
iso-hsemolysin by virtue of which the corpuscles react
with serum of Group III.

The appearance of the different groups can now be
further explained in terms of the Mendelian theory.
According to the conception of the individual formulated
by Mendel, each cell of the body contains an ingredient
derived from each of the sexual cells or gametes which

88 BLOOD TRANSFUSION

united at the moment of fertilization of the ovum by the
spermatozoon to form the individual. But when the adult
in his or her turn forms sexual cells or gametes, these
ingredients separate again, half the gametes containing
one of the pair of factors, half containing the other. This
process certainly takes place during the rearrangement
of the nuclear substance or chromosomes at the cell
divisions which result in the formation of the ripe sexual
cells. It is called the " segregation of the gametes."

In the present case the unit character producing Group
II will be first considered. As already explained, the
factors concerned may be called A and a, and the individual
of Group II may be constituted by AA or Aa, and the
gametes, therefore, may contain either A or a, but not both.
The individuals resulting from the union of the gametes
derived from Aa adults may then be constituted in three
ways — AA, Aa, or aa. Similarly for the unit character
producing Group III, the factors concerned may be called
B and b, and the individual of this group may contain BB
or Bb. The gametes then contain either B or b, and the
individual resulting from their luiion may again be con-
stituted in three ways — BB, Bb, or bb.

In computing the results, however, it must be remem-
bered that most, or perhaps all, people are hybrids, so that
both unit characters are present simultaneously, and all the
factors must be taken into account. It is easily seen that
the gametes derived from a hybrid individual must contain
one of the following combinations :

AB, Ab, aB, or ab,
and consequently the individuals formed from them must
have one of the following constitutions ;

AB— Ab, Ab— aB, aB— ab, ab— ab, AB— AB,-

AB— aB, Ab— ab, aB— aB,

AB-ab, Ab-Ab.
This includes all the possible combinations that can result
from the chance union of the gametes, and it is now clear

PHYSIOLOGY OF BLOOD GROUPS 89

which blood groups result from which combinations, if it
be remembered that

A is dominant to a,

JJ fi 99 JJ D)

and that

Group I results from the presence of both A and B.
,, II » „ 9, 99 „ A only.

>5 ll-l- >> JJ JJ JJ JJ -t> JJ

„ IV „ „ ,, absence ,, both A and B.

Thus Group I may be constituted by AB— AB.

AB-aB.

AB-Ab.

AB-ab.

Ab-aB.
Group II may be constituted by Ab— Ab. i

Ab— ab.
>> III j> 5> >j JJ ^b aB.

aB-aB.
J, IV „ „ „ „ ab— ab.

It now becomes evident what offspring may result from
the union of parents who have any of the above constitu-
tions. Thus parents both of Group I may have off-
spring belonging to any group according to which of the
five possible constitutions they possess. If the union be
represented by

AB-AB X AB-AB,

then only offspring of Group I can result, since every
gamete contains both A and B. The other possibilities
may be worked out by the reader if he desire.

Similarly, a union of Groups I X II, I X III, or II X III
may produce any of the groups, definite limitations being
imposed by the detailed constitution of the parents. On
the other hand, the remaining group unions that are
possible can only produce a more limited variety of off-
spring. Thus II X II or II X IV can only produce

90 BLOOD TRANSFUSION

Groups II or IV ; III X III or III X IV can only produce
Groups III or IV ; IV X IV can only produce Group IV.

The Mendelian theory of inheritance in general has been
subjected to a prolonged and widely ramifying series of
tests, and it seems in the present state of knowledge to
present a satisfactory and consistent explanation of the
facts. For a more extended accoimt of it the reader must
be referred to the standard works on the subject.^ As
regards its application to the present case, the test of
actual experiment has not yet been carried out on a large
scale. A series of observations has, however, been pub-
lished by J. R. Learmonth, who, taking forty families at
random, determined the blood groups of both parents and
the children in each family. In this way he tested most
of the possible group matings, and, with a single exception,
the group inheritance conformed to the theory as set out
above. Additional confirmation of the truth of the theory
is afforded by the pedigree given on the page opposite.
I have recently collected this pedigree, which includes fifty-
nine individuals belonging to four generations, and it has
not been published before. It will give, perhaps, a more
graphic representation of the facts than has been conveyed
by the brief summary contained in the foregoing pages.
It does not show any variation from the results that were
to be anticipated according to the theory.

The exceptional result obtained by Learmonth in one
of his forty families serves to emphasize the clarity of the
theoretical considerations. In this family parents both
belonging to Group IV had a child showing the reactions
of Group I. There are three possible explanations of this :

(1) The observations were at fault.

(2) The putative father was not the real father.

(3) The Mendelian theory of inheritance is wrong.

The Mendelian theory is established on so firm a basis
that, in the absence of more numerous exceptions, (3) may
be rejected. There is no reason for supposing that the

1 Mendelism, R. C. Punnett, 5th ed., Macmillan, 1919.

go

o <

OS

a w
^ 15

2 ^

^■«

0 o

* Hi

1 w

pt.

91

92 BLOOD TRANSFUSION

observations were inaccurate, and we are therefore brought
to the conclusion that in such a case the child is illegitimate.

The conclusions which emerge from this structure of
theory and fact are obviously of very great clinical im-
portance. It is now clearly demonstrated that a mother
belonging, say, to Group I, may give birth to a child belong-
ing to any one of Groups I, II, III, or IV ; her blood may
not be used for transfusing her child without a grave risk
that the " maternal threat " may culminate in the death
of the child. The same applies to the possible relations
between a father and his child. Two brothers, again, may
belong to Groups II and III respectively. Even the blood
of twins may be mutually incompatible, except in the rare
case of " identical twins," who, it may be supposed on
theoretical grounds, would certainly belong to the same
group, though I am not aware of a case in which this has
been put to the test. As much care, therefore, must be
exercised in testing the blood groups of members of the
same family before performing a transfusion as would be
taken before using a donor who is not related to the patient.

The medico-legal importance of the facts concerning the
inheritance of blood groups is also evident, and, although
this test has not yet been used as a test of legitimacy, there
can be little doubt but that it will be so used in the near
future. The information to be derived from it is of a
negative rather than a positive character. Thus the
occurrence of Group III blood in a child whose mother is of
Group II and putative father of Group I cannot be taken
as a proof either of legitimacy or the reverse. But if, as
in Learmonth's case, parents both of Group IV have a
child of Group I, or if parents both of Group II have a
child of Group I or III, then this may be taken as a proof
of illegitimacy.

There is not much experimental evidence concerning the
effect of various pathological conditions on the agglutina-
tion reactions of the blood and serum. It has already been
mentioned that there is no proof that the possession of any

PATHOLOGY OF BLOOD GROUPS 93

particular blood group confers upon its owner any special
immunity from, or liability to, disease. The numbers,
investigated by Alexander in the communication referred
to on p. 81, are too small for the observation to be of much
value ; it is also necessary, as a preliminary to any such
research, to demonstrate that there is no abnormal altera-
tion in the reactions of the blood of these patients. It is
probable, indeed, that evidence of this alteration in malig-
nant disease already exists, for a reference to it is to be
found in Kolmer's work on serum-therapy,^ but I have been
unable to find a record of the investigation.

I possess, on the other hand, evidence that an alteration
may take place in some other diseases, such as pernicious
anaemia and familial, or acholuric, jaundice. Evidence
for the former was provided recently by a patient whose
condition was typical, clinically, of the last stages of the
disease. Her corpuscles, tested with stock sera, belonged
to Group II, but her serum, tested directly with the
corpuscles of prospective donors known to belong to Group
IV, agglutinated these vigorously, so that a transfusion
could not safely be performed. The same phenomenon has
been found by other observers. In acholuric jaundice
there is a progressive destruction of red corpuscles in the
patient's circulation. This appears to be connected in
some way with an abnormal functioning of the greatly
enlarged spleen, since the destruction of corpuscles ceases
almost at once when this organ is removed. There seems
to be, in addition, an alteration in the blood reactions. In a
case which I tested recently, the patient's corpuscles were
quickly agglutinated by serum of Group III, and he there-
fore nominally belonged to Group II. His serum, however,
when separated and tested against other bloods of known

1 J. A. Kolmer, Injection, Immunity , and Specific Therapy, ed. 2, Saunders
Co., 1917, p. 287 : " With the increasing number of blood transfusions
the phenomena of iso-agglutination and iso-haemolysis are of consider-
able practical importance, especially if the patient is suffering from
cancer, when the serum is likely to be actively haemolytic for the donor's
corpuscles." No authority is given.

94 BLOOD TRANSFUSION

groups gave, in addition to a rapid agglutination of cor-
puscles belonging to Group III, a definite, though slower,
agglutination of corpuscles belonging to Groups II and IV,
showing that it had acquired abnormal properties.

It is possible that there are similar alterations of reactions
in other pathological conditions. The instances mentioned
above suggest that the serum is affected rather than the
corpuscles, but further investigations are needed. It is an
observed fact that blood outside the body soon develops
the property of auto -haemolysis. If blood is drawn from a
vein, put into a test-tube, and allowed to clot, then after
twenty-four hours or more the serum which has separated
from the clot begins to be tinged with haemoglobin, even
though it has remained absolutely sterile. It appears,
therefore, that the serum develops a haemolysin and the
corpuscles the corresponding iso-haemolysin, the interaction
of which results in the breaking up of corpuscles. If this
process takes place in normal blood outside the body, it
would not be surprising to find that it may also occur
abnormally inside the body. This actually happens in
the condition known as paroxysmal haemoglobinuria. The
pathology of the disease is obscure, but it seems that a
haemolysin develops in the serum as the result of cooling
in the extremities and haemolysis takes place when the
cooled serum is again warmed by being restored to the
general circulation. The presence of this haemolysin in
addition to the normal haemolysins has been demonstrated
by Moss. It is possible that a similar though less acute
change takes place in acholuric jaundice. Blood trans-
fusion, therefore, is not likely to be efficacious in such
conditions, since the transfused corpuscles may be
destroyed whatever the apparent blood group of the
patient. Some of the facts of auto -haemolysis have been
recently investigated by Bond, but it is not necessary to
give the details here. He concludes that the development
of auto-haemolysins, which are non-specific and independent
of the specific haemolysins of the blood groups, has a

PATHOLOGY OF BLOOD GROUPS 95

biological significance in the history of the red corpuscle,
and is a product of ageing. The biochemistry, however,
of the process remains at present entirely unknown.

The necessity for careful blood grouping in every case
before performing a transfusion has now been sufficiently
emphasized, but before proceeding to the description of
the methods of choosing a donor and of grouping, a
possible danger must be mentioned which may arise even
when the blood groups are known. In the preceding
chapters references were made to the effects which have
been observed to follow repeated transfusions given in the
treatment of a condition such as pernicious anaemia. In
such cases, although the groups were ascertained, and the
bloods were also tested directly against one another with-
out any incompatibility being detected, yet when the third
or fourth transfusion was given, symptoms of toxaemia
followed, sometimes with haemolysis. The death of the
patient has even been hastened in this way. A very
striking instance of this phenomenon, which has been
recently reported (278), will serve to bring home the reality
of the danger. A boy was transfused by the citrate method
with blood from his father, and this was followed only by
a mild febrile reaction such as is often observed. Eighteen
days later a second transfusion with blood from the same
donor was performed, and after 150 cc. had been given, a
severe reaction resulted, which was followed later by pro-
nounced haemoglobinuria. In this case the bloods of donor
and recipient had been tested against one another directly,
but this was not repeated, and the groups were not ascer-
tained until afterwards. Probably there was some error
in the original test, for it afterwards appeared that the boy
belonged to Group I and his father to Group III, so that
there should have been agglutination of the boy's corpuscles
by his father's serum outside the body. Nevertheless,
Group I individuals have been called the " universal
recipients," and no ill effects are usually observed whatever
blood be used for transfusing them. In the other cases

96 BLOOD TRANSFUSION

already mentioned a reaction followed the later transfusions,
even when the donor and recipient belonged to the same
group. It appears that by repeated transfusions the
recipient becomes as it were sensitized to the blood of
another individual even of the same group, and conse-
quently great caution must be used in giving the later
transfusions of a series. Some light is thrown on this
question by the observations of Ottenberg, already referred
to, concerning the artificial production of iso-hsemolysins
in cats. In these animals iso-agglutinins are found, but
iso-haemolysins seldom or never. The reaction is, however,
found to become ha^molytic in the recipients of transfusions,
and it is then selective. It seems, therefore, that the
group reactions may not be as clearly defined as was at
one time supposed. Probably there are slight incom-
patibilities of an unknown nature between individuals of
the same or compatible groups. These are very seldom
of any consequence in a first transfusion, but become
accentuated as the result of " sensitization," and in later
transfusions have a pronounced influence. This " over-
lapping " of groups has been mentioned on another page.
It must not be supposed that any untoward results follow
repeated transfusions as a general rule, for usually no such
effect is observed. In order, however, to minimize the risk,
it may be suggested that the following precautions should
be taken : (1) The donor should be actually of the same
group as the recipient, and not merely of a theoretically
compatible group ; a patient, for instance, of Group II
should receive blood of Group II rather than of Group IV.
(2) The same donor should not be used for the later
transfusions of a series, on the grounds that the sensitiza-
tion appears to be an individual rather than a group
phenomenon. (3) In performing the later transfusions,
the blood should be given at first very slowly, so that it
may be discontinued at the first appearance of any signs
of a reaction.

CHAPTER VI

THE CHOICE OF BLOOD DONOR

The physiology of blood groups having been examined, the
principles governing the choice of a blood donor can be
more readily understood. It is evident that this choice is
determined largely by blood groups, and in the present
chapter therefore the clinical methods of testing for the
groups will be described.

Before, however, the bloods can be tested, a willing
donor must be found, and this is not always an easy matter.
During the war, even when transfusion was being practised
on a large scale, there was never any difficulty in finding
volunteers among the men that were more lightly woimded.
In addition to the genuine and ready response which many
men would make at once to a call for help in a matter of
life and death, there was the glamour of novelty and the
feeling of satisfaction following an act of conscious heroism
— for such the sacrifice of blood was held to be, the days
having long been forgotten when as much blood was " let '*
in the treatment of almost any ailment. In the Ex-
peditionary Force, too, the unofficial reward of a fortnight's
leave in England proved a potent inducement, and the
rejection of a volunteer on the ground of incompatibility
was regarded almost as an injustice or as a reflection upon
the physical condition of the candidate. In civilian life,
however, such inducements cannot be held out, and it will
be found that many a man " does not like the idea " of
parting with a pint of blood, even though the sacrifice may
save another's life. Often, however, a near relative of the
patient may happen to be willing and suitable, or, failing

7 97

98 BLOOD TRANSFUSION

this, in a hospital ward there will usually be some young
man who has been admitted for a slight operation, such
as the radical cure of a hernia, and will accede to a request
for blood if the procedure, its object, and its harmlessness
to himself be briefly explained. Notoriety is fortunately
seldom a motive for volunteering, and though paragraphs
have occasionally appeared in the daily press with head-
ings such as " Police Inspector's Sacrifice," this has
probably not been done by the donor's own wish. It is,
after all, natural that to the mind of a layman the giving
to another of so personal a possession as his blood should
seem to be an act of heroism, and it is also natural that
occasionally a man should feel some repugnance to taking
part in a strange performance which he but dimly under-
stands. To the young, on the other hand, the procedure
may appeal by its faint flavour of adventure.

Occasionally during the last two years advertisements
for blood donors have appeared in newspapers, probably
not in vain. If the demand for blood donors becomes
greater than it has been as yet, it will certainly result in
the creation of a class of " professional blood donors," who
already exist in some numbers in the United States of
America, where blood transfusion is a more widely recog-
nized form of therapeutics than it is in this country.
These professionals have even formed a Trade Union, so
that as high a fee as possible may be obtained from those
who need their blood. Apart from this, some of the
advantages of having these professionals available have
already been explained in the chapter on the dangers of
blood transfusion. It is evident that certain sources of
danger can be eliminated in advance, and in an emergency
it is obviously better to have donors of known groups
available, so that no time is lost in testing the prospective
donors of whom several in succession may be found un-
suitable. Probably it will be easier for practitioners to
arrange for such professionals to be available at the
shortest notice than for necessary arrangements to be made

THE CHOICE OF BLOOD DONOR 99

in a hospital. Even in large institutions it is usually
difficult for any of the men employed in them to be spared
from their work for twenty-four hours, so that, although
suitable men of known groups are always within call, it
may be impossible to use them. This, however, is not the
place to discuss the organization that is necessary to make
a blood transfusion a really efficient form of emergency
treatment in a hospital. It may merely be observed that
in every hospital it should be possible to give a blood trans-
fusion to a patient suffering from urgent haemorrhage
within fifteen minutes of his arrival on the premises.

Whether the donor be a " professional " or an
" amateur," it may be useful to mention a few points to
be observed in choosing him. There can be no doubt that
the most satisfactory individuals for the purpose are young
men between the ages of eighteen and twenty-five. The
younger the donor, the less likely is he to be suffering from
certain of the diseases mentioned in the chapter on the
dangers, the less will be the immediate effect of the with-
drawal of circulating fluid, and the more quickly will he
recuperate from the loss of blood.

It must not be supposed, however, that the withdrawal of
even 1,000 cc. of blood will usually have an appreciable effect
upon a healthy man. It is impossible to predict from the
donor's appearance what immediate effect the loss of blood
will have upon him. It sometimes happens that the most
robust-looking individual becomes faint after losing a few
hundred cubic centimetres, whereas another, to all
appearances pallid and much less satisfactory, will not
evince the slightest discomfort from the loss of 750 cc. or
even more. Normally a man should be able, by his
physiological mechanisms, to compensate reflexly and at
once for the removal of this amount of fluid from his
circulation. In any case, the worst effect that is seen in a
well-chosen donor is a transient faintness ; it is usually
wise to keep him on his back for two or three hours after
the operation, and he should not, if it can be avoided,

100 BLOOD TRANSFUSION

return to his work on the same day. During the late war
a medical officer of my own acquaintance gave 750 cc. of
blood for a severely wounded friend and continued his
arduous duties as Surgical Specialist in a Casualty Clearing
Station immediately afterwards. In this case, however,
the donor was solely responsible for his own welfare ;
usually this responsibility rests upon another, and greater
care must be exercised. The effect, indeed, of a trans-
fusion upon the donor seems to depend more upon psycholo-
gical than upon physiological factors. A nervous and
excitable donor is more likely to suffer than one who
approaches the operation without apprehension. This is
another point in favour of employing a professional donor,
who soon becomes familiar with the whole procedure and
will lose all symptoms of fear.

The same considerations may be applied to the use of
women as blood donors. In them the spirit of self-sacrifice
is commonly more highly developed than it is in men, and
some of the most eager donors will be found among them.
The disability of nervousness will, however, occur more
often in women, and another consideration of importance
is that the veins of a woman are usually much less easily
accessible than those of a man. Not only is the abundant
subcutaneous fat an impediment in women, but usually the
superficial veins are all of small size. The method of
choice for performing a blood transfusion will be presently
described, and it will then be seen that the operation is
easier and that much less damage is inflicted on the donor
if a large superficial vein can be tapped. In women this
will very often be difficult or even impossible. In general,
therefore, it may be stated that the use of women as blood
donors is to be avoided. The fallacies concerning the
indiscriminate transfusion of an infant with its mother's
blood and of any patient with the blood of a near relation
have already been explained.

THE CHOICE OF BLOOD DONOR 101

Testing for Blood Groups

Reference to the table of blood reactions given on p. 71
will show that in order to discover the blood group of any-
individual it is only necessary to test his corpuscles against
the serum of Groups II and III. These reactions may be
recapitulated as follows :

(i) If he be Group I, his corpuscles will be agglutinated
by the serum of Groups II and III.

(ii) If he be Group II, his corpuscles will be agglutinated
by the serum of Group III only.

(iii) If he be Group III, his corpuscles will be agglu-
tinated by the serum of Group II only.

(iv) If he be Group IV, his corpuscles will be agglutinated
by neither serum.

Only the serum, therefore, collected from people known
to belong to Groups II and III need be kept in stock.
This can generally be obtained from the Lister Institute,
and if kept sterile will retain its agglutinating properties
for some months, but under no circumstances should serum
more than six months old be used, since the consequences
of a failure to agglutinate may be very serious. Neverthe-
less, the agglutinins contained in serum are very resistant
to physical and chemical changes in their environment.
Dried serum has been successfully used for testing purposes,
and Culpepper has shown that the reactions are not inter-
fered with by cold or by heat until actual coagulation of
the serum takes place. Bacterial contamination does not
affect the reactions, so that the serum is still active even
when putrid. Various methods have been used for pre-
serving the serum. Its properties are not affected by the
addition of dilute cresol (1 : 250) or of chloroform.

In the absence of any stock sera, the agglutinating test
may be applied directly. A few cubic centimetres of blood
are taken from the patient, and the serum as soon as it has

102 BLOOD TRANSFUSION

separated is tested against the corpuscles of the prospective
donor. If agglutination occurs, this donor is at once
excluded. If no agglutination occurs, he is either of the
same group as the patient or belongs to a compatible group.
Supposing that a donor actually of the same group as the
patient is wanted, then the reverse test must be performed
in addition, that is to say, the corpuscles of the patient
must be tested against the serum of the donor. If both
tests are negative, then donor and patient are proved to
be of the same group. The method of direct test cannot
be applied in an emergency owing to the loss of time
involved ; it is better, therefore, that anyone who intends
to be ready to perform a blood transfusion should always
have serum of Groups II and III immediately available.

The collection of stock sera is not a matter of any diffi-
culty. With strict aseptic precautions 20 cc. of blood are
withdrawn in a syringe from persons known to belong to
Groups II and III ; the bloods are put into a sterile test-
tube and allowed to clot. As soon as the serum has
separated it is drawn up into sterile glass bulbs of suitable
capacity, which are sealed off at each end. The most
convenient form of storage for actual use is a capillary glass
tube sealed at each end. Each tube may be made to hold
a single drop, which is the amount used for a test. There
is then no wastage of serum, and no chance of contaminat-
ing the remaining stock. When the blood has been with-
drawn and has clotted, the complete settling of the
corpuscles can be hastened by the use of the centrifuge.
If the serum be left in contact with the corpuscles for more
than twelve hours, some auto -haemolysis may take place,
so that the serum will become tinged with haemoglobin.
It is exceedingly important that the two stock sera should
not become confused, and this may easily happen unless
each tube has some distinguishing mark.

The methods of testing for blood groups have been
simplified by successive observers since the existence of the
groups was first demonstrated in 1907. Moss used an

THE CHOICE OF BLOOD DONOR 103

elaborate technique such as was essential for putting a
new discovery upon a secure scientific basis. In order to
obtain a suspension of corpuscles, blood was drawn into a
syringe containing a solution of sodium citrate to prevent
clotting. The corpuscles w^ere collected by means of the
centrifuge, and were thoroughly washed twice in normal
saline solution so that they were finally collected free from
serum and from citrate. Serum was collected in the
manner already described. A series of small tubes was
then filled with equal quantities of serum and the sus-
pension of corpuscles, and was incubated for two hours at
37-5° C. At the end of this time observations were made
and again after the tubes had stood for twelve hours in
an ice chest. Varying degrees of agglutination and
haemolysis were then accurately recorded, and far-reaching
results were obtained.

Later workers had the advantage of using stock sera
belonging to known groups, so that the number of observa-
tions to be made was very greatly reduced. Brem intro-
duced in 1916 a method of testing in which he mixed the
serum and suspension of washed corpuscles in very small
quantities on a coverslip, which was inverted over an
ordinary cell slide rimmed with petroleum jelly. The
results could then be observed macroscopically or under the
microscope, and the presence or absence of agglutination
could be determined within fifteen minutes. The detection
of haemolysis by the hanging drop method requires that
the cells should be incubated and observed at intervals
for several hours, but it is not always easy to see the
disintegrated corpuscles xmless the process has taken
place extensively. The diagram on p. 105 gives in a
tabulated form some idea of the appearances presented
by the corpuscles of the different groups when mixed with
the stock sera and observed in a hanging drop imder a
microscope. Agglutination must be distinguished from
the formation of rouleaux, which may be seen in any of
the mixtures.

104 BLOOD TRANSFUSION

For scientific purposes these very careful tests are
necessary, but it seems to be clear that for clinical pur-
poses a much rougher and quicker test is adequate. In
the clinical determination of blood groups it is superfluous
to carry the test to the point of watching for haemolysis, for
it is upon the presence of agglutinins in the serum and the
corresponding iso-agglutinins in the corpuscles that the
determination of the groups depends. Further, no error
is introduced by neglecting the haemolysis, since it has
been shown that haemolysis is invariably preceded by
agglutination. It is the occurrence of agglutination there-
fore that is of prime clinical importance. If that is
excluded, haemolysis is necessarily excluded also, and the
prolonging of the test is seen to be only of academic interest.
In the methods described above the corpuscles were always
tested in the form of a washed suspension. This precaution
was taken on the supposition that the presence of any of the
serum belonging to the corpuscles might interfere with the
reaction. If, however, the amount of this serum be small
relatively to the amount of the test serum, then no such
interference takes place.

The ordinary clinical method of testing may therefore
be greatly simplified, and the one commonly used at the
present time is as follows : A single drop of each of the
stock sera is placed on two glass slides, or, better, side by
side upon a white glazed tile or plate, the numbers of the
groups, II and III, being written above the respective
drops. The lobe of the ear of the person to be tested is
then washed with ether and pricked with a sterile surgical
needle. A small quantity of the blood which exudes is
taken up on the end of a blunt metal or glass rod, and is
intimately mixed with the drop of serum under the number
II. The end of the rod is then carefully wiped clean, and
a similar small quantity of blood is mixed with the drop of
serum marked III. The amount of blood to be used should
not be so great as to make the drop of too deep a colour,
which may interfere with observation of the reaction, but

GROUP II.
SERUM

CROUP III.
SERUM

GROUP I.
CORPUSCLES

AGGLUTIhlATIOM

AGGLUTItNATIOH

GROUP II.
CORPUXLtS

NO AGGLUTIMATIOrs

AGGLUTirSATIOM

GROUP III.
CORPUSCLES

AGGLUTirSATIOM

NO AGGLUTIINATION

no AGGLUTIMATIOM

GROUP nil.
CORPUSCLE.5

no AGGLUTIMATlOn

Fig. 7. — Tabulation of Serum Reactions as seen in Hanging Drops.

105

106 BLOOD TRANSFUSION

it should be enough to impart to it a very definite red tint.
The slide or tile is then gently rocked, so that some slight
movement is imparted to the drops, which are at the same
time closely watched in a good light. The agglutinating
reaction is readily seen with the naked eye, especially
against the white background provided by the tile. If
the serum be properly active, the agglutination of the
corpuscles begins to be apparent as a definite granular
appearance resembling brick dust within a minute of
mixing. With a little practice this appearance is easily
recognized, but it must be distinguished from the appear-
ance produced by a mechanical gravitation of the corpuscles
towards the centre of the drop. If agglutination is taking
place, the granulation appears simultaneously throughout
the drop, and not only in the centre. With an active serum
the process may proceed rapidly, so that in less than five
minutes the corpuscles have been aggregated into a few
irregular masses ; often it stops short of this, but the drop
presents, nevertheless, a coarsely granular appearance which
is quite unmistakable. If no granulation can be seen at
the end of five minutes, it can be assumed that the test is
negative for the serum of that group, and the group of the
corpuscles may be deduced upon the principles already
explained.

The test carried out in this way is admittedly not
susceptible of the same finesse as if it were done with the
assistance of the hanging drop, the incubator, and the
microscope ; nevertheless, my own experience in a large
number of cases has shown that, clinically, this test may
be relied upon, and the same view has been expressed by
other writers on the subject. Very seldom is there any
doubt as to the presence or absence of agglutination.
When doubt exists, it is easy to repeat the test and obtain
a confirmation of the result. It may perhaps be urged
that this test is quite insufficient for eliminating the
slighter degrees of incompatibility which have produced
serious results when the transfusion has been repeated

THE CHOICE OF BLOOD DONOR 107

several times. But in the cases reported, the blood that
was used had not shown any agglutination even when most
carefully observed under the microscope. It seems, there-
fore, that the results were probably due to another
factor, as already suggested (see p. 57), which the more
elaborate test failed to eliminate. The efficiency of the
rapid test is therefore not invalidated. It is, nevertheless,
in the present state of knowledge, a wise precaution to
perform the direct test between patient and donor in
addition to the group test when circumstances permit. It
is essential when the patient is suffering from any form of
blood disease. It is unnecessary when the transfusion is
to be performed as a life-saving operation in haemorrhage
or shock.

CHAPTER VII

THE METHODS OF BLOOD TRANSFUSION

Some reference has already been made in the first
chapter to the rapid development in recent years of the
technique of performing a blood transfusion. The earlier
operators, owing to the difficulties introduced by the
coagulation of blood outside the body, were constrained
to make use of some method of direct transfusion, the blood
flowing directly from an artery of the donor into the
patient's veins. This has now been largely replaced by one
of the methods of indirect transfusion, the blood being
withdrawn from the donor into a vessel in which clotting
is delayed or prevented, and then injected or allowed
to run into the patient's circulation.

Direct Transfusion. — The obvious method of performing
a direct transfusion is by making an end-to-end anasto-
mosis between an artery of the donor and a vein of the
recipient. The most readily accessible artery is the radial
at the wrist, and this is indeed almost the only artery that
is available. The most accessible vein is the median basilic
or the median cephalic at the elbow. The operation of
end-to-end anastomosis, using an artery of so small a
calibre as the radial artery at the wrist is usually found to
be, is one of great technical difficulty ; this effectually
prevented transfusion from being used at all frequently.
A modification has been used by Sauerbruch and others,
in which the end of the radial artery is drawn into the
lumen of the vein through a slit in its wall. A suture is
passed through the radial artery close to its cut end, and
the needle is then passed through the slit in the vein and

108

METHODS OF BLOOD TRANSFUSION 109

out again through the wall of the vein an inch or so higher
up. Traction on the suture then pulls the artery into the
vein. The artery has meanwhile been temporarily occluded
by a clip, which is removed when the artery is inside the
vein, so that the blood can then flow from one to the other.
This is easier to do than the anastomosis, but, in addition
to the other objections to direct transfusion to be mentioned
presently, the difficulty occurs of occlusion of the artery by
the physiological process of inversion of its coats at the
cut end. This is likely to happen before much blood has
passed, so that apparent success at first is often not
maintained. Sauerbruch claimed that the amount of
blood that had passed could be estimated by measuring
the time taken for 1 cc. of blood to flow from the artery
before it was introduced into the vein ; but there is no
proof that the rate of flow remains constant.

If direct transfusion be desired, there can be no doubt
that Crile's method, introduced some fifteen years ago, is
the best to employ. After much patient work Crile per-
fected a method of anastomosis which ensures that no
occlusion of the vessels can take place at the site of junction.
This depends on the use of a short silver tube, through
which the end of the artery is threaded. The artery is
then pulled back again outside the tube in the form of a
cuff and fixed in position. The end of the artery has thus
been made rigid, and over this the vein is pulled in its turn
and fixed by a ligature. A watertight junction is thus
made, and blood can flow through it without interruption —
unless clotting takes place in the vessels as the result of
handling and injury to their walls. This method has been
extensively used in America, and it was the first to render
the operation of transfusion a comparatively popular one.

Various other devices for achieving the same result have
been elaborated by other workers, and attention may be
drawn to those of Elsberg and Bernheim, both of which are
described in the book by the latter on " Blood Trans-
fusion." During the war a simpler method was introduced

110 BLOOD TRANSFUSION

by Colonel Andrew Fullerton, who, working at a Base
Hospital in France, found that he could get good results by
employing a thin rubber tube with a small silver cannula
at either end. The apparatus was first coated on the
inside with a thin layer of paraffin wax, in order to dis-
courage clotting within the tube, and the cannulas were
introduced into the donor's artery and the recipient's vein
respectively. The blood could then flow freely from one
to the other. The fact that blood was being transmitted
was taken to be proved by the visible pulsation of the thin
rubber connecting-tube synchronously with the arterial
pulsations. The disappearance of this was assumed to be
evidence that clotting had occurred. This method was
described by Colonel Fullerton to the surgeons working at
the Casualty Clearing Stations, where blood transfusion
was likely to be of most service, but it was never used
extensively. The coating of the inside of the tube with
paraffin is in itself an operation of some difficulty. Under
conditions in which any loss of time could not be permitted,
success by this method was not attained with sufficient
certainty, and it was shortly afterwards replaced by the
more satisfactory methods described below. The most
recent work on direct transfusion has been done by J. M.
Graham at Edinburgh, who has however reached the con-
clusion that the technique is always more difficult than
that of indirect transfusion.

It can easily be seen, therefore, that all the known
methods of direct blood transfusion present great technical
difficulty, which renders the method unsuitable for general
use. There are, in addition, certain other objections to it
of an obvious nature. It is, in the first place, impossible
to measure the amount of blood which has passed from the
donor to the recipient. Sometimes an indication may be
obtained from the evident improvement in the condition
of the patient, accompanied by the signs of loss of blood
in the donor. More often clotting takes place, unknown
to the operator, at some point, with the result that blood

METHODS OF BLOOD TRANSFUSION 111

ceases to pass a considerable time before the end of the
operation, and the patient has consequently received very
much less blood than is supposed. It has been claimed by
Libman and Ottenberg that the amount of blood trans-
ferred may be estimated by weighing the donor before and
after the operation. This presupposes that a very accurate
weighing machine is easily available, which usually is not
the case.

A second objection is the extent of the injury which is
necessarily inflicted on the donor. His radial artery must
be exposed through an incision of considerable length, and
must be ligatured at the conclusion of the process. The
operation becomes, therefore, a matter of some moment to
the donor, who will be permanently scarred, and can under
no circumstances be used for transfusion more than twice.
A third objection is that the transfusion cannot be done
with due regard to the condition of the patient. A delicate
and difficult operation has to be performed with the donor
and recipient lying side by side, their arms close together.
It is therefore almost imperative that both should be on
operating-tables of a convenient height. Often, however,
with an exsanguinated patient it is very important that he
should not be moved from his bed, but as a bedside opera-
tion direct transfusion becomes difficult indeed !

A final objection is that in some people the radial artery
is of very small calibre, so that when all preparations have
been made, and the artery exposed, it is found to be quite
impossible to proceed. Another element of uncertainty is
thus introduced.

There is, therefore, little to be said in favour of direct
transfusion, and much to be urged against it. This method
has, indeed, in my own opinion, come to be of historical
interest only. For this reason the different methods have
only been very briefly described. For more detailed
information, reference must be made to the various original
communications, which will be found in the Bibliography.
Indirect Transfusion. — The methods of indirect

112 BLOOD TRANSFUSION

transfusion may be divided into those which depend upon
the use of an anticoagulant mixed with the blood and those
in which the blood is given unaltered. The technique of
either process is simple compared with that of direct
transfusion, though any method which makes use of whole
blood can never be quite as free from uncertainty or
difficulty as one which introduces the use of an anticoagu-
lant. If the blood is prevented from clotting, the chief
cause of failure in performing blood transfusions is removed.
"With any whole-blood method of transfusion speed is
exceedingly important, frequent practice is a very great
advantage, and it is essential, as with direct transfusion,
that the donor and recipient should be in close proximity
to one another, if not actually side by side.

On the other hand, the use of an anticoagulant renders
speed and frequent practice of less account. The blood
can be drawn, and can then be put on one side until the
best moment for giving it has arrived. Due regard may
be had to the patient's condition, since the blood can be
carried about and can be given at leisure to the patient in
his bed without disturbing him and almost without his
knowing it. The donor, too, is not exposed to the mental
shock of lying for some time side by side with a patient who
may be in extremis, or may even expire during the operation.

There are, however, those who consider that the use of
whole blood, instead of blood which has been chemically
treated, has advantages which outweigh the possible dis-
advantages mentioned above. Two methods of using
whole blood are, therefore, described first ; the use of
anticoagulants is then described in detail, and their
advantages and possible dangers are enlarged upon.

Whole Blood Transfusion with Syringes. — It is
obvious that, if blood can be drawn from the donor's vein
into a glass syringe and injected into the recipient so
rapidly that clotting has no time to occur, then a trans-
fusion of any quantity of blood that may be wished can be
given by this simple means. The measure of the amount

METHODS OF BLOOD TRANSFUSION 113

of blood transfused is given by the number of syringes that
have been filled and emptied. This method has been
successfully used by several workers, and it has the
advantage that no very special apparatus is necessary.
It does, however, require that several syringes, and more
than one assistant, should be available, since clotting will
take place in the syringes, unless they be frequently washed
out. There is also the possibility that clotting may take
place in the needle which is introduced into the donor's
vein, since this cannot be withdrawn and replaced for each
syringeful of blood that is transferred. With practice,
however, and with good assistants, the process can be done
quickly enough to avoid this. Wide -bore needles with
short rubber connexions are introduced into the veins of
donor and recipient ; if, as often happens, this is difficult
to do through the skin in the case of the recipient, his vein
must first be exposed through an incision and a glass or
metal cannula introduced into it. The operator then fills
the syringes with blood in quick succession and hands them
to his first assistant, who injects the blood into the recipient.
Blood is prevented from escaping from the needles when
the syringes are disconnected by nipping the rubber con-
nexions with the fingers. The first assistant passes the
empty syringes to the second assistant, who washes them
out with normal saline, and hands them back if needed to
the operator. This can be done with six 20 cc. syringes
used in rotation, possibly with only four.

The most recent description of this method has been
published by J. M. Graham of Edinburgh, who has intro-
duced an improved form of needle. This consists of a
double tube ; the inner tube has a needle point which is
used for puncturing the vein, and can be withdrawn into
the blunt outer tube when the vein has been entered.
Any further wounding of the vein is thus avoided. In
addition, movement of the needle-cannula is prevented by
a bull-dog forceps attachment, which is clipped to the skin.
Graham finds it advisable to lubricate the cannulae and
8

114 BLOOD TRANSFUSION

syringes with vaseline before being used. He also states
that : "As the absence of clotting depends upon the
rapidity with which the syringes are filled and emptied,
a series of syringes should be used in strict rotation, and
all trace of blood must be washed out with saline before
the syringes are used again. One or two additional
assistants are necessary for this method." The dis-
advantages are evident, and it is not suitable for general use.

A modification of the method has been described by
Unger, in which only one syringe is used. The barrel of
this is cooled by an ether spray so that clotting is dis-
couraged or prevented.

Whole Blood Transfusion with Kimpton's Tube. — The
principle of this method depends upon the use of paraffin
wax as a coating for the vessel into which the blood is
drawn, so that clotting is prevented or greatly delayed.
The form of the vessel has been modified by different
workers, but the essentials are the same in each. One
form of the apparatus, known as the Kimpton-Brown tube,
is illustrated in the accompanying diagram. It consists
of a graduated glass cylinder, of about 700 cc. capacity, the
lower end of which is drawn out into a cannula point at an
acute angle with the body of the cylinder ; the point is of
a size convenient for introducing into a vein and its bore
large enough to allow of a free flow of blood through it.
Near the upper end is a side tube to which a rubber tube
can be attached, and an opening at the top is closed by a
rubber bung. An ordinary rubber double-bulb bellows
is the only other apparatus that is needed.

The glass vessel is first sterilized in the autoclave, and
then it must be coated on the inside with a thin layer of
paraffin wax. The whole success of this method depends
upon this wax coating being absolutely complete right up
to the tip of the cannula at the bottom. If the tiniest area
of glass be left exposed in the cannula, the process will fail.
The production of this perfect wax coating used to be
exceedingly difficult of attainment without very frequent

Fig. 8. — Kimpton-Brown Tube

115

116 BLOOD TRANSFUSION

practice. The apparatus was first raised to exactly the
right temperature ; sterile, melted paraffin was then put
into it, and distributed evenly over the surface, excess being
allowed to run out. The apparatus was then cooled down,
and could be put away in a sterile towel ready for use,
great care being taken that the lumen of the cannula was
patent and not blocked with excess of wax. A simplifica-
tion of the process was introduced by the use of a saturated
solution of wax in ether. This solution is put into the
vessel, which must not be heated, and is made to rim all
over the surface, excess as before being allowed to escape
through the lower opening. The ether quickly evaporates,
leaving a very thin and perfect film of wax over the surface
of the glass. As before, it must be ascertained that the
lumen of the cannula is patent. The apparatus is then
ready for use.

The donor and recipient need not be lying close together,
but they must be in the same room. A vein is exposed in
the arm of each by dissection under a local anaesthetic.
The operator then picks up the vein with a pair of dissect-
ing forceps, and makes an oblique cut into the lumen as
in the diagram on p. 131. A flap is thus made which is
held in the dissecting forceps in the left hand or is picked
up with a fine-pointed pair of artery forceps. The Kimp-
ton's tube is taken in the right hand, and the point of the
cannula is introduced into the vein ; that part of the
lumen lying opposite the flap serves as a gutter which
guides the cannula directly into the lumen, so that it is
introduced without any fumbling or delay. The cannula
is pushed on so that its widest part engages the whole
circumference of the vein, forming a joint through which
blood does not leak. The cannula having been pushed well
up into the vein, the forceps holding the venous flap may be
let go. At the same time an assistant grips the donor's
upper arm, or some form of tourniquet of the necessary
degree of tightness is applied, so that the veins become
congested without obliteration of the arterial pulse. Blood

METHODS OF BLOOD TRANSFUSION 117

now flows rapidly into the tube, and the venous pressure
is always sufficient to overcome the counter-pressure of the
increasing head of fluid in the tube. It is imnecessary,
therefore, to produce any negative pressure within the tube
with a reversed Higginson's syringe or an exhaustion
pump, which has been used by some workers. Blood is
allowed to flow into the tube until the requisite amount
has been obtained. The venous congestion is then released,
and at the same time the tube and cannula, held at the
lower end with the right hand in such manner that the
index finger is free, is withdrawn from the vein. At the
moment of withdrawal the end of the cannula is closed with
the right index finger. To prevent haemorrhage from the
donor's vein, a ligature previously put round it is tied by
an assistant, or pressure on it is maintained with a sterile
swab. The operator must now, without a moment's delay,
carry the tube filled with blood over to the recipient. An
opening in his vein is made by an assistant in the same
manner as already described, the finger is removed from
the cannula, and its point is instantly introduced into the
vein. It is now necessary to produce some degree of
positive pressure in the tube to ensure that the blood shall
at once begin to flow steadily into the vein. This is done
with a rubber bellows, attached by an assistant to the
upper side tube, and the level of the blood in the tube
should at once begin to fall. Great care must be taken
that the positive pressure is released before the tube is
completely emptied of blood in order to avoid the obvious
danger of the entry of air into the patient's vein. When
the tube is nearly empty it is withdrawn, the vein is
ligatured, and the wounds in donor and recipient are
sutured. The most convenient pattern of Kimpton-Brown
tube holds only about 500 cc. of blood, so that if more is
needed, the process must be repeated.

There is virtually only one cause of failure in transfusion
by this method, and that is the occurrence of clotting in
the cannula or at the bottom of the tube. If it does occur

118 BLOOD TRANSFUSION

at any stage of the operation, it cannot be remedied. It
may happen when the tube is nearly full ; if so, the blood
that has been withdrawn cannot be used. Clotting may
be due to an imperfection in the paraffin coating on the
glass, but if there is any delay from any cause, it may take
place independently of this. The method is therefore
never absolutely certain of success even in the hands of an
expert, and for general use it is certainly unsuitable. It
was introduced into the British Army by some of the
American surgeons in 1917, and was used by the writer
under the guidance of Major Alton of the Harvard Medical
Unit during the first battle of Cambrai with good results.
Many of the English surgeons, however, soon abandoned
it as a routine method in favour of anticoagulants. There
are other objections to it besides its uncertainty. A vein
must be exposed by dissection in both donor and recipient,
so that avoidable injury is inflicted on the former. It is
not a perfectly clean method, some blood necessarily
escaping at each successive stage in the process, though an
expert can reduce this to a minimum. In the hands of a
novice it may occasion a very bloody scene. The whole
operation is one of urgency, and the best interests of donor
and recipient cannot always be considered.

Modifications have been introduced, such as that of
Vincent, who uses an attachment with a needle instead of
the glass cannula point. This obviates some of the
objections, but introduces other difficulties, such as the
necessity for coating the inside of the needle with paraffin
wax. The technique can certainly be acquired, and the
method has rendered excellent service in the past, but it
has no obvious advantages except the uncertain one of
avoiding chemical treatment of the blood.

Transfusion with Anticoagulants. — It will have
become evident from the descriptions of the transfusion of
whole blood already given, how great a difficulty is
introduced into the technique of these methods by the
physiological process of clotting in blood outside the body.

METHODS OF BLOOD TRANSFUSION 119

It is clear how much the process of transfusion would be
simplified if the clotting were to be prevented. Something
has already been said in the historical sketch of the various
means by which this problem was attacked, and it need
only be stated here that the most suitable substance for
this purpose has been found to be sodium citrate. This
method was introduced by Lewisohn as recently as 1915,
and it soon became the method of choice among most of
those who tried it.

The process of the formation of a blood clot has always
been one of the great problems of physiology, and numerous
theories have been propounded to explain it. The theory
accepted at the present time regards the process as a
complicated one depending on the presence in the blood of
a number of different factors. This theoretical explana-
tion may be represented diagrammatically as follows :

Plasma TtsQues and piabeiebQ

Prothrombtn Ca salts Thromboklnase

Fibrinogen ^Thrombin

FLbrlrt

The clot consists of fibrin in which blood corpuscles are
entangled. It is clear that if any one of the reacting agents
can be removed or rendered inert the clotting cannot take
place. There is only one inorganic substance taking part
in the reaction, and it is this factor that is more easily
removed than any of the others. Calcium is precipitated
in an insoluble form by various chemical reagents, but it is
obvious that for purposes of transfusion the formation of
an insoluble precipitate is not permissible. It is therefore
necessary to use a substance which will form a soluble

120 BLOOD TRANSFUSION

compound with the calcium and which is at the same time
harmless when introduced into the circulation. The only
substance which has been found at present to possess both
these properties is citrate of sodium. This forms with
calcium a soluble double salt, in which calcium is rendered
inert. It is usually held that the calcium to be active must
be present in the ionized form, but recent investigations by
Vines into the role of calcium tend to modify slightly
the accepted view of its action. He has shown that calcium
is present in the blood in two forms, ionized and combined,
and that both take part in the coagulation reaction. He
has, in addition, demonstrated that a quantity of anticoagu-
lant sufficient to combine with the whole of the calcium
present in a given quantity of blood is not enough to
prevent coagulation. It seems, therefore, that the anti-
coagulant acts by combining with a large organic molecule
of which calcium is only one constituent, and not merely
by combining with ionized calcium. The organic complex
with which the calcium is associated possibly corresponds
to the thrombokinase of the theory.

About the time that the use of the citrated blood was
introduced by Lewisohn, some investigations upon animals
were carried out by Salant and Wise in order to determine
how sodium citrate was dealt with and eliminated by the
body. These observers found that it very quickly dis-
appeared from the circulation, nearly 90 per cent, of the
salt having been got rid of within ten minutes of its
intravenous injection. Part of the citrate is destroyed by
oxidation, and the rest, 30 to 40 per cent., is eliminated by
the kidneys, the urine being rendered alkaline. It was
also shown that if a very large dose was ^iven, so large that
toxic symptoms resulted, the effect was rapidly obtained ;
but that if the toxic dose were not fatal, no remote effects
followed. Its injection never resulted in any albuminuria.

Lewisohn showed by experiment on the human subject
that up to 5 grammes of sodium citrate in the form of a
0-2 per cent, solution could be injected intravenously with-

METHODS OF BLOOD TRANSFUSION 121

out any harmful results. It was also shown that this con-
centration of the salt was sufficient to prevent clotting
outside the body, and that the microscopic appearance of
the blood cells was not altered by the admixture of this
solution.

Theoretically, therefore, the amount of citrate that
should be used as an anticoagulant should be 2 grammes
for 1,000 cc. of blood, or 100 cc. of 2 per cent, solution for
900 cc. of blood. In practice it is better to err on the side
of safety and to use a slight excess of citrate. This amount
of citrate should be used for the 750 cc. of blood which
constitutes the ordinary maximum amount of blood used
in a transfusion. For smaller quantities of blood the
amount of citrate may be correspondingly reduced.

The use of citrated blood was introduced to the British
Army in France in 1917 by Oswald Robertson, who re-
commended the use of a larger amoimt of citrate than this.
His object in increasing the amount was to produce a
solution which, when diluted with the correct amount of
blood, would be isotonic with it. It was thought that a
hypotonic solution might result in some damage to the
red corpuscles by osmosis, and Robertson therefore re-
commended the use of 160 cc. of a 3-8 per cent, solution of
citrate, which, when mixed with 750 cc. of blood, will give
a solution of which the osmotic pressure equals that of
0*9 per cent, saline solution. It may be doubted, however,
whether this consideration is of more than theoretical
importance. There can be little doubt that in practice
the effect of a slightly hypotonic solution, such as is given
by the 100 cc. of 2 per cent, solution of citrate, is negligible
as regards destruction of corpuscles. If, however, it be
thought necessary, an isotonic solution may be produced
by the addition of sodium chloride. Other considerations,
as will be seen shortly, weigh in favour of giving the
smaller amount of citrate. The dosage to be recommended,
therefore, on practical and experimental grounds is 2
grammes of citrate in 100 cc. of water for 900 cc. of blood.

122 BLOOD TRANSFUSION

or 1 gramme of citrate in 50 ec. of water for 450 cc. of blood
or less. These proportions need not be observed very
accurately. Latitude may be used in either direction
without harming either the transfused blood or the
patient.

It has been stated above that sodium citrate introduced
into the circulation in small quantities, such as are sufficient
for anticoagulant purposes, is non -toxic to man. In the
light, however, of the extended experience of the last four
years, it is seen to be possible that this statement may not
be quite literally true. Probably there is an individual
variation in the tolerance of different people to sodium
citrate. Certainly in some cases a reaction follows the
injection of citrated blood. The symptoms of this reaction
are a slight headache, a rise in temperature to two or three
degrees above normal, sometimes accompanied by a rigor
or a sensation of chill, and an increase in the pulse rate.
The effect is, however, always very transitory, lasting only
two or three hours, and is never, in my own experience,
attended by any symptoms which need give rise to anxiety
for the patient's welfare ; nor does it in any way prejudice
the therapeutic results of the transfusion.

That the reaction is caused by the citrate and not by
another constituent of the transfused blood has been
believed by several observers. In a case seen by the writer
a slight citrate reaction occurred in a youth who acted as
blood donor. The transfusion was carried out by a modi-
fication of the syringe method, which involved the injection
at intervals of a syringeful of citrate solution into the
donor's circulation. The possibility that the reaction was
produced by another factor was therefore not present in
this instance.

Nevertheless, it must be admitted that citrate has not
yet been absolutely proved to be the cause of this slight
reaction in all the cases in which it occurs. Evidence has,
indeed, been brought forward by Lewisohn and by Meleney
to show that citrate is definitely not responsible for the

METHODS OF BLOOD TRANSFUSION 123

reaction. The statement is made that some reaction occurs
after 10 per cent, of all transfusions, and that this percentage
is unaffected whether whole blood or citrated blood is used.
Lewisohn has himself investigated the effects in a long
series of parallel cases in which different methods were
employed, and he reports that the results following the use
of citrated blood were as good as with any other method.
Drinker states that reactions follow the use of citrated
blood slightly more often than they do that of whole blood,
but this has not been confirmed. He was unable to find any
impurity in the citrate that might be held responsible. It
is quite possible that all the reactions observed are in
reality caused by the " minor agglutinins " mentioned on
p. 73. Meleney has noticed that the blood of some
donors is more likely to produce a reaction than that of
others ; this suggests that the responsibility rests with the
blood and not with the citrate. The occurrence of a toxic
reaction constitutes the only real objection to the use of
citrated blood that has yet been brought forward, but even
this has not yet been fully substantiated ; in any case, the
reaction is of so little importance that it is greatly out-
weighed by the numerous advantages that are conferred
by the use of citrate. The possibility that a citrate reaction
does sometimes occur may be taken as an indication in
favour of using the smaller amount recommended by
Lewisohn rather than the larger dose used by Robertson.
The experience of a great many observers has established
the fact that citrated blood is quite as effective as whole
blood in its therapeutic effects.

It is convenient to have the sodium citrate in a form
ready for immediate use. I have therefore been in the
habit of keeping it in the solid form in small stoppered
bottles, each containing 1 gramme of the salt. These are
sterilized at 130° C, and can be kept indefinitely until
wanted. If 450 cc. of blood or less are to be drawn, the
contents of one bottle is shaken into the transfusion flask ;
50 cc. (approximately 2 oz.) of sterile warm water are

124 BLOOD TRANSFUSION

added, in which the citrate will rapidly dissolve. If more
than 450 cc. of blood is to be used, the contents of two
bottles must be dissolved in 100 cc. or 4 ozs. of water.
Alternatively a concentrated solution of citrate may be
kept in sealed ampoules, but the salt is less stable in
solution, and I prefer to keep it in the solid form.

The ideal method of blood transfusion seems to me to
require that it shall be absolutely certain of success, that
the blood shall not necessarily be injected into the patient
immediately it has been drawn, so that other circum-
stances besides the demands of the transfusion operation
can be considered, and that no injury shall be done to the
donor beyond the puncturing of a vein. In addition to this,
the method should be so simple and free from special
apparatus that it can be easily learnt and carried out by
one operator without skilled assistance. All these require-
ments are fulfilled by the citrate method, and a satisfactory
method of performing this will next be described. As will
be seen, the blood can be drawn with the minimum amount
of injury to the donor ; when drawn, it can be put on one
side, for several hours if necessary, and then given to the
patient at whatever may be judged to be the most favour-
able moment ; the whole process can be carried out by
a single operator without any assistance ; and finally, but
little practice is needed to make success certain every time.

The transfusion apparatus known as " Robertson's
bottle," first described by Oswald Robertson in 1918, is
the basis of most citrate methods. This could be easily
improvised in a field laboratory, and was extensively used
during the last year of the war. The apparatus consisted
of a glass bottle of about a litre capacity, the mouth of
which was closed by a rubber bung. Through the bung
three glass tubes passed. One, connected by a short
rubber tube with a wide-bore needle, ended about an inch
from the bottom of the bottle; through this the blood
flowed into the bottle. A second tube, which reached to
the angle between the side and the bottom of the bottle.

METHODS OF BLOOD TRANSFUSION 125

was connected by a rubber tube with a cannula ; through
this the blood was injected into the patient. The third
tube reached only just beyond the bung, and to this was
attached a Higginson's syringe, by means of which either
negative or positive pressure would be produced inside the
bottle, according to which end of the syringe was attached.
It is unnecessary to describe this apparatus any further,
for it was found by myself and others that it could be with
advantage modified in the direction of simplicity. It is
in the first place unnecessary in drawing the blood to
create any negative pressure if a needle of a large enough
bore ( 2 or 3 mm.) be used, and, further, it is an advantage
not to have the needle attached in any way to the bottle,
which, as the blood flows into it, has to be freely agitated
in order to mix the blood quickly with the citrate. The
needle may, therefore, be attached to a rubber tube of
suitable length which hangs freely into the collecting
vessel as shown in the diagram on p. 127. The third tube
of " Robertson's bottle " may be dispensed with by using
a conical flask provided with a side tube to which a rubber
bellows can be attached. The delivery tube is therefore
the only one that need pass through the rubber bung.
This tube should have an angle in it inside the flask so that
its lower end reaches into the corner, and the extremity
should be groimd down obliquely so that, although it
reaches right into the corner, it does not become occluded
by too accurate contact with the surface of the vessel.
By this means any wastage of blood is prevented. I have
found it a very great convenience to introduce into the
delivery tube just outside the flask an air-lock,^ the value
of which will be seen shortly. To the barrel of this air-lock
a rubber tube with a cannula is attached. Close to the
cannula is some form of clip. The whole apparatus is
illustrated in the figure on p. 133, and with the help of this
its use may be readily understood.

^ This embodies the same principle as the " dropper " designed by R. D,
Laurie.

126 BLOOD TRANSFUSION

The particular form of needle which I have been in the
habit of using is shown in the figure. Its lumen has a
diameter of 2 mm., and the steel tube ends off flush with
the wide shoulder to which the rubber tube is attached.
This avoids any recess within the needle in which clotting
may begin. The point of the needle should not be too long,
in order that it may not wound the opposite side of the vein
when it has been introduced. For ease of introduction,

Fig. 9. — Tbansfusion Needle (Actual Size)

however, the extremity should be very sharp and should
have cutting edges. The point and edges should be touched
up on a bevelled hone each time before the needle is used.
The needle should be kept ready for immediate use in
liquid paraffin. I have found that the most convenient
way of keeping it is to put it into a test-tube containing
paraffin, which is plugged with cotton-wool and sterilized
at 130° C. in the hot air oven or by careful heating over
a flame. In this way the needle may be kept ready for an
indefinite time without any chance of its rusting. When
it is taken out of the test-tube, a sterile rubber tube is
slipped on to it and it is then ready for use. As an addi-
tional precaution, a small quantity of paraffin may be
drawn up into the rubber tube, which is thus lubricated on
the inside, but this is not absolutely necessary. The tube
must be sterilized with the rest of the apparatus, as rubber
is destroyed by liquid paraffin.

When the donor's arm has been congested by gripping
it above the elbow, or better by the application of a
tourniquet ^ drawn to the requisite degree of tightness, a
suitable vein, usually the median basilic, is chosen. The

1 A very convenient form of tourniquet is that designed by R. G. Canti.
It is sold by Messrs. Maw & Sons, and by Messrs. Allen & Hanburys.

METHODS OF BLOOD TRANSFUSION 127

area of puncture is washed with ether and a very small
quantity, 2 to 3 minims, of 2 per cent, novocain is intro-
duced over the vein with a hypodermic syringe. If a larger
quantity is used, the vein may become obscured, but this

Fig. 10. — Drawing Blood for Transfusion

small amount may be dispersed by a few moments' pressure
with the finger, and is usually enough to anaesthetize the
very small area of skin that is to be operated upon. A tiny
cut in the skin is then made with the point of a scalpel, and
the needle is pushed through into the vein. If the donor's
vein is a large one, such as is usually found in the type of

128 BLOOD TRANSFUSION

donor recommended in a previous chapter, this is quite
easy to do. To make it equally easy if the vein be smaller,
it has been suggested by Watson that the vein may be
fixed by pushing an ordinary fine sewing-needle through
the skin at right angles to the line of the vein, into the
vein, and out again through the skin. This needle is held
with the forefinger and thumb of the left hand, while the
right hand pushes the transfusion needle into the lumen
of the vein just below it. When the needle is in the vein,
the blood flows out rapidly through the tube which hangs
into the flask containing the citrate, as illustrated. This
flask is held by an assistant, who mixes the blood with the
citrate by gently swinging it. If a properly adjusted
tourniquet is kept on the donor's arm while he works his
forearm muscles by clasping and unclasping his hand, a
flow of blood is obtained which is fast enough to prevent
clotting in the needle, and indeed is quite as fast as most
donors can tolerate. Blood up to 1,000 cc. may be col-
lected in this way in ten to twenty minutes. If the vein
be of a good size, it makes no difference whether the needle
be inserted towards the heart or away from it. When
enough blood has been collected, the tourniquet is removed,
the needle is withdrawn, and pressure is maintained with
a sterile swab over the site of puncture for a few minutes.
No further bleeding will take place after this, and no suture
is needed. The donor's part in the operation is then
finished. He should be made to lie on his back for a few
hours afterwards, and given plenty of fluids, but beyond
this no special precautions are necessary.

When the blood has been drawn, and has been satis-
factorily mixed with the citrate, the flask may be put on
one side until it is wanted, its mouth having been closed
with a cotton-wool stopper. If the blood is wanted at
once, the flask may be stood in a basin of warm water to
keep it at body temperature. Otherwise it may be allowed
to cool, and can be warmed up again when it is to be
administered. The citrated blood may be kept for a con-

METHODS OF BLOOD TRANSFUSION 129

siderable time without undergoing any appreciable change
in its therapeutic value. It has been given twelve hours
or more after being taken with the same good effects as if
it had been newly drawn. During the war advantage was
taken of this fact to anticipate during quiet times the
necessity for many transfusions during times of stress.
The blood was drawn in some quantity and kept for
several hours in an ice chest, so that it was readily available
during the expected battle. Recently I have administered
to a woman who had been operated upon for a ruptured
ectopic gestation 600 cc. of citrated blood which had been
kept for twenty-seven hours at room temperature after
it was drawn. The effect was in every way as satisfactory
as if it had been freshly drawn, and there was no sign of
any toxic reaction. So far as I know, blood had not ever
been kept so long as this before being used, but there does
not seem to be any objection to so doing.

When the blood is to be given, the delivery tube with the
rubber bung is inserted in the flask, and the corpuscles
which have gravitated to the bottom are distributed again
through the fluid by gently shaking it. In administering
the blood, it is very often advisable to inject it through a
cannula which is tied into a vein. If the patient is a woman,
it will usually be found that the veins are small and buried
in fat. Also many transfusions will be given to combat
the collapse due to shock and haemorrhage, in which case
the veins will be empty and the use of a cannula will be
found essential. Sometimes, however, the patient will
have large veins which can be readily distended ; this may
sometimes be encouraged by keeping the arm for half an
hour beforehand in a bath of hot water. Under these
circumstances the blood can be given through a needle
introduced in exactly the same way as has already been
described in the case of the donor. In the following
account of the process it will be assumed that the use of a
cannula is necessary.

When choosing a vein in the patient, the operator must be
9

130 BLOOD TRANSFUSION

guided by circumstances. Usually the median basilic will
be the most convenient, and if, in a collapsed patient, this
is invisible, previous knowledge of the position of the vein
must determine the site of the incision. If another opera-
tion is being done simultaneously upon the upper part of
the patient's body, it may be more convenient to use the
internal saphenous vein in Scarpa's triangle, or even one
of the superficial veins about the ankle. In administering
blood to an infant, several methods have been used. These
are described separately at the end of the present chapter.
Whatever vein be chosen, the line of the incision is first
infiltrated with a small quantity of a 2 per cent, solution of
novocain. The vein is then dissected out, and is ligatured

Fig. 11. — Transfusion Cakkula (Actual Size)

near the lower end of the incision. A ligature is also put
loosely round the upper part. The operator now takes the
barrel of the air-lock, which, together with the attached
rubber tube and cannula, is filled with 0-9 per cent, saline
solution, all air bubbles being carefully excluded. The
tube is clipped near the cannula, so that the whole system,
including the cannula, remains filled with the fluid. The
form of the cannula used will depend upon the operator's
particular preference, but a type which I have found very
convenient is shown in the accompanying figure. It is
made of glass, and its extremity is ground down at an angle,
which makes it very easy to introduce into the vein. The
slight constriction near this end ensures that it can be
securely tied into the vein and that no leakage round it
shall occur. This is very necessary, because there is some-
times a considerable pressure to be overcome, due to veno-
spasm in a collapsed patient, before the blood begins to
flow.

An oblique cut is now made in the vein, as shown in the

METHODS OF BLOOD TRANSFUSION 131

illustration, the cannula is introduced, and the upper
ligature is tied.

The barrel of the air-lock, with its contained saline
solution, is then fixed firmly on to the rubber bung, so that
the nozzle of the delivery tube projects into the saline
solution. Meanwhile, an assistant has fixed a rubber
bellows on to the side tube of the flask ; a short piece of
glass tubing loosely packed with cotton-wool should be
interposed between the bellows and the flask to prevent
any particles of dust being blown over into the flask from

Fig. 12. — Insertion of the Cannula in a Vein

the bellows, which is not sterilized. The clip near the
cannula is released, and some positive pressure is produced
inside the flask by means of the bellows. The citrated
blood then rises in the delivery tube, and a corresponding
quantity of saline solution is displaced from the air-lock
into the patient's circulation. The blood then flows from
the nozzle of the delivery tube into the air-lock, and the
remainder of the saline solution is driven on into the
patient. Finally the blood flows steadily through the
cannula, and the rate at which it is flowing can be observed
in the air-lock.

The presence of this air-lock facilitates, as has been seen,
the introduction of the cannula into the vein, since there
is no leakage of blood to obscure the operation. In addi-
tion, the operator can see at a glance whether the blood is

132 BLOOD TRANSFUSION

flowing in properly, and can regulate the rate of flow to a
nicety by varying the pressure in the flask by means of the
bellows. If a very slow injection is required, the blood can
even be made to run drop by drop. If the patient is
suffering from acute anaemia, the blood can be pumped in
rapidly, 750 cc. of blood being given in the course of
twenty minutes. If, on the other hand, the patient has a
plethora of fluids, such as is seen in some cases of secondary
anaemia, the blood must be given very much more slowly
than this, since it is dangerous rapidly to increase the blood
volume. A half to three-quarters of an hour must be
occupied in giving 500 cc, and even then the patient may
complain of a sensation of tightness in the chest and of
dyspnoea, due to embarrassment of the right heart during
the transfusion. This complaint, however, is usually
transient, and will disappear quickly if the injection be
stopped for a few minutes.

It has been said that the lower end of the delivery tube
reaches into the angle between the side and the bottom
of the flask. When therefore the flask is nearly empty, it
should be tilted so that very nearly the whole of the blood
can be forced up the tube. When the flask is quite empty,
the blood in the barrel of the air-lock must be carefully
watched, and when its level has fallen to the bottom of
this, the clip must be applied to the tube above the cannula.
By this means no blood is wasted except the small
quantity which remains in the tube below the air-lock.
As soon as the tube has been clipped the cannula is with-
drawn, the vein is ligatured above the opening into its
lumen, and the edges of the skin incision are sutured.

Transfusions carried out in this way can be performed
with uniform success. The technique is simple and
straightforward at every stage, and can be easily demon-
strated and learnt. It is, in addition, a perfectly clean
process, and not a single drop of blood need be spilt. Any
method which involves the injection of blood under
pressure is open to the objection that it is possible to over-

METHODS OF BLOOD TRANSFUSION 133

look the fact that the flask has been emptied and to kill
the patient by injecting air into his veins. This can, how-
ever, only happen as the result of great carelessness on the
part of the operator. The presence of the air-lock affords

Fig. 13. — Injection of the Blood, showing use of Air-lock

an additional safeguard, as it can hardly escape the
operator's notice that blood has ceased to flow from the
nozzle of the delivery tube.

The method may also be criticized on the ground that
some damage is caused to the corpuscles of the donor's
blood by the shaking which is necessary to mix it with the

134 BLOOD TRANSFUSION

citrate solution. This objection is, in my opinion, theoreti-
cal rather than practical. If, however, it be desired to
avoid any such shaking, the apparatus designed by A. E.
Stansfeld and described by him in 1918 may be used.
This ensures that the citrate and the blood flow into the
containing vessel together, so that no further mixing
is needed. The apparatus is more cumbrous, more
fragile, and less easy to clean and to sterilize than
that described above. In the hands of an expert it will
give excellent results, but its use requires some little
practice, and it is therefore not so well adapted for
general use.

The whole of my own apparatus, as described above,
may be obtained from Messrs. Allen & Hanburys, Wigmore
Street, London, W.l, who also provide a convenient box
for carrying it.

Transfusion of Infants. — The technique of transfusions
performed upon children over the age of about four years
docs not differ from that used for adults, except that less
blood is to be given. The antecubital veins are much
smaller and a finer cannula may have to be used, but this
is the only source of trouble. The transfusion of infants
and very young children may, however, be found to be
much more difficult. The operation will have to be done
for conditions such as melaena neonatorum, which was
discussed on p. 48 of the present work, or for post-
operative collapse, such as may follow an operation for
congenital hypertrophic stenosis of the pylorus, for in-
tussusception, or for some of the more extreme cases of
harelip and cleft palate. In all such instances the trans-
fusion will be a matter of some urgency. Speed and
certainty will depend on previous knowledge of the best
method to be employed.

In the case of melsena neonatorum treated by R. D.
Laurie, which has been already referred to, a needle was
introduced into one of the antecubital veins, and 20 cc. of
citrated blood were injected with a syringe. This method,

METHODS OF BLOOD TRANSFUSION 135

however, is not to be recommended, on account of its great
difficulty.

The method used by Helmholtz and also by Howard
depends on the introduction of a syringe needle into
the superior longitudinal sinus through the anterior
fontanelle. A needle two to three inches long attached to
a 20 cc. syringe is inserted near the upper angle of the
fontanelle at an angle of about 25° with the scalp. As the
needle pierces the wall of the sinus, a sensation of resistance
is experienced, similar to that given by the piercing of the
dura mater in doing a lumbar puncture. Blood should
then be allowed to enter the syringe in order to demon-
strate that the point of the needle really is lying in the
sinus. Abnormalities have occasionally been met with,
in which the sinus was situated to one side of the middle
line or was very much smaller than usual. The danger of
injecting the blood in such a case into the brain or the
subdural space need not be emphasized. Difficulty may
also be caused by restlessness on the part of the child, and
to overcome this Helmholtz has devised an apparatus
which grips and fixes the child's head at a suitable angle.
All this, however, makes the process unnecessarily elabor-
ate. As an alternative, Vincent has exposed one of the
internal jugular veins into which he introduces a cannula.
This again is a comparatively difficult operation, which
may leave a permanent scar in a conspicuous place. Vin-
cent had previously used the femoral vein, but he found this
difficult to approach, and the wound was apt to become
contaminated afterwards.

The method of choice is undoubtedly that used by Bruce
Robertson, who has performed a much larger number of
transfusions upon infants and children than any other
worker in this field of surgery. He has found that the
internal saphenous vein near the ankle is a vessel possessing
a fairly wide lumen and thick walls even in infants, so that
a needle or cannula can be introduced into it with com-
parative ease and rapidity. The vein must, of course,

136 BLOOD TRANSFUSION

be freely exposed through an incision, but its situation
removes any objection there might otherwise be to this
operation. Robertson has usually employed the syringe-
cannula method described earlier in the present chapter,
but there is no objection to the use of an anticoagulant.
The small amount of blood to be given, 15 cc. per pound
of body weight, makes the use of the transfusion flask
unnecessary. It is better to use a 20 cc. syringe, into
which 2 cc. of a 10 per cent, solution of sodium citrate is
drawn as a preliminary. The needle in the donor's vein
and the cannula in the infant's saphena should each be
provided with a rubber connexion, which can be clipped, or
pinched by an assistant, when the syringe is not attached.
The syringe containing the citrate is filled with blood and
injected into the infant as often as may be necessary until
the total amount decided upon has been given.

Robertson has used this method for complete replace-
ment of the circulating blood in treating streptococcal
septicaemia following erysipelas, and for shock in children
due to burns. The infant's blood is removed through the
anterior fontanelle, while a fresh supply is injected into
the saphenous vein. Complete replacement has not, so
far as I know, ever been performed upon an adult, but the
process is feasible, given a large enough assemblage of
donors. In this way some vieillard might attempt the
rejuvenation, which at present, as we are told, has only been
obtained from the transplantation of " monkey glands "
by Viennese professors.

BIBLIOGRAPHY

1. ADDIS, T. : "The effect of intravenous injections of

fresh human serum and of phosphated blood on the
coagulation time of the blood in hereditary haemophilia."
Proc. Soc. Exp. Biol, and Med., 1916, xiv. 19.

2. AGOTE, L. : " Nuevo procedimiento para la transfusion

del sangre." Anales del Inst, modelo de clin. med.
Buenos Ayres, Jan. 1915.

3. ALBINI : " R^lazione sulla trasfusione diretta di sangue

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4. ALEXANDER, W. : " An enquiry into the distribution

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5. ANDERS, J. M. : " Transfusion of blood in pernicious

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6. ARCHIBALD, A. : " The transfusion of blood in the

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7. ASHBY, W. : " The determination of the length of life

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8. AVELING, J. H. : " An improved apparatus for immediate

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9. B ARRIS, J., & DONALDSON, M. : " Acute inversion of

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10. BAYLISS, W. M. : " Intravenous injection in wound

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11. BAYLISS, W. M. : " Intravenous injections to replace

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12. BAYLISS, W. M. : " The toxicity of haemolysed blood."

Brit. Journ. Exp. Path., 1920, i. 1.
137

138 BLOOD TRANSFUSION

13. BAYLISS, W. M., and others : " Acidosis and shock."

Rep. of the Med. Res. Com., vii., 1919, 245.

14. BAZETT, M. C. : " The value of haemoglobin and blood

pressure observations in surgical cases." Rep. of the
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15. BELINA, DE : " De la transfusion du sang defibrine."

Paris, 1873.

16. BELKNAP, R. W. : " Suggestions for identification of

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724.

17. BELL, W. B. ; " The treatment of eclampsia by trans-

fusion of blood." Brit. Med. Journ., 1920, i. 625.

18. BENEDICT, N. B. : " On the operation of transfusion

— being the report of a committee." Nezv Orleans
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19. BERARD, L., & LUMIERE, A. : '' Technique for trans-

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20. BERNHEIM, B. M. : "An emergency cannula." Journ,

Am. Med. Assoc., 1912, Iviii. 1007.

21. BERNHEIM, B. M. : " Therapeutic possibilities of trans-

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22. BERNHEIM, B. M. : " Hemolysis following transfusion

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23. BERNHEIM, B. M. : " A simple instrument for the

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24. BERNHEIM, B. M. : " The limits of bleeding considered

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25. BERNHEIM, B. M. : " Blood transfusion, haemorrhage

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26. BERNHEIM, B. M. : " Whole blood transfusion and

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27. BISCHOFF, T. L. W. : " Beitrage zur Lehre von dem

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28. BLASIUS : " Statistik der Transfusion des Blutes."

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BIBLIOGRAPHY 139

29. BLOOMFIELD, A. : " The results of treatment in per-

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30. BLUNDELL, J. : " Experiments on the transfusion of

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31. BLUNDELL, J. : " Some account of a case of obstinate

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32. BLUNDELL, J. : " Some remarks on the operation of

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33. BOND, C. J. : '' On auto-haemagglutination." Brit.

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34. BOWCOCK, H. M. : " Serious reactions to repeated

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35. BREM, W. V. : " Blood transfusion with special reference

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36. BREWER, G. E., & LEGGETT, N. B. : '' Direct blood

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38. BUCHSER, J. : "A successful case of transfusion."

Med. Rec, 1869-70, iv. 337.

39. BUERGER, L. : "A modified Crile transfusion cannula."

Journ. Am. Med. Assoc, 1908, li. 1233.

40. BULGER, H. A. : " Blood changes in a case of haemo-

philia after transfusion." Journ. Lab. and Clin. Med.^
1920, vi. 102.

41. BULLIARD, H. : " Modifications sanguines apres trans-

fusions." Journ, de Physiol, et de Path. Gen., 1921,
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42. BURMEISTER, W. H. : " Resuscitation by means of

preserved living erythrocytes in experimental illumi-
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Ixvi. 164.

140 BLOOD TRANSFUSION

43. CANNON, W. B. : " Shock and its control." Am. Joiirn.

Physiol, 1918, xlv. 544.

44. CANNON, W. B. : " Acidosis in cases of shock, hfemor-

rhage, and gas infection." Report of the Med. Res.
Com., ii. (3), 1919, 85.

45. CANNON, W. B. : "A consideration of the nature of

wound shock." Report of the Med. Res. Com., ii. (5),
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46. CANNON, W. B., FRASER, J., & COWELL, E. M. :

" The preventive treatment of wound shock." Report
of the Med. Res. Com., ii. (6), 1919, 125.

47. CANNON, W. B., FRASER, J., & HOOPER, A. N. :

" Some alterations in the distribution and character of
the blood." Report of the Med. Res. Com., ii. (2), 1919,
72.

48. CARTER, W. S. : " An experimental study of the use of

sodium citrate in the transfusion of blood by direct
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49. CHARLES, R., & SLADDEN, A. F. : " Resuscitation

work at a casualty clearing station." Brit. Med. Journ.,
1919, i. 402.

50. CHAVASSE, F. B. : " The blood group in mother and

child." Brit. Med. Journ., 1921, i. 641.

51. CHERRY, T. H., & LANGROCK, E. G. : " The relation

of haemolysis in the transfusion of babies with the
mothers as donors." Journ. Am. Med. Assoc., 1916,
Ixvi. 626.

52. CLOUGH, P. W. & M. C. : " Study of reactions following

transfusion of blood." South. Med. Journ., 1^21, xiv.
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53. COLE, H. P. : " Transfusion and pellagra." Journ. Am.

Med. Assoc, 1911, Ivi. 584.

54. COOLEY, T. B., & VAUGHAN, J. W. : "A simple

method of blood transfusion." Jour^i. Am. Med. Assoc.,
1913, 435.

55. COWELL, E. M. : " The initiation of wound shock."

Report of the Med. Res. Com., ii. (4), 1919, 99.
5Q. COX, R. : " Blood transfusion in the seventeenth century."
Journ. Am. Med. Assoc, 1914, Ixii. 222.

BIBLIOGRAPHY 141

57. COX, T. : "An account of another experiment of trans-

fusion, viz. of bleeding a mangy into a sound dog."
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58. CRILE, G. W. : '* The technique of direct transfusion of

blood." Ann. Surg., 1907, xlvi. 329.

59. CRILE, G. W. : " Haemorrhage and transfusion." Apple-

ton & Co., N.Y., 1909.

60. CROTTI, A. : " Indirect transfusion of blood." Surg.

Gynec. and Obstet., 1914, xviii. 236.

61. CULPEPPER, W. L. : " Report on five thousand bloods

typed, using Moss's grouping." Journ. Lab. and Clin.
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62. CURCHOD, H. : " Transfusion of blood." Rev. med,

de la Suisse. Rome, 1920, xl. 666.

63. CURTIS, A. H., & DAVID, V. C. : " Transfusion of

blood by a new method, allowing accurate measure-
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64. DALE, H. H., and others : " Surgical shock and some

allied conditions." Brit. Med. Journ., 1917, i. 381.

65. DALE, H. H., and others : " Traumatic toxaemia as a

factor in shock." Rep. of the Med. Res. Com., viii.,
March 1919.

66. DARWIN, ERASMUS : Zoonomia ; or the Laws of Life.

London, 1794. 2 vols., 4°. Vol. i. p. 373; vol. ii.
pp. 120, 605, 676.

67. DAVID, V. C, & CURTIS, A. H. : " Experiments in the

treatment of acute anaemia by blood transfusion and
by intravenous saline infusion." Surg. Gyn. and
Obstet., 1912, XV. 476.

68. DAVID, V. C, & CURTIS, A. H. : " Recent experiences

with blood transfusion." Journ. Am. Med. Assoc,
1914, Ixii. 775.

69. DAWSON, P. M. : " The changes in the heart rate and

blood pressures resulting from severe haemorrhage and
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70. DENYS, J. : "A letter concerning a new way of curing

sundry diseases by transfusion of blood." Philosophical
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71. DENYS, J. : "An extract of a letter touching a late

142 BLOOD TRANSFUSION

cure of an inveterate phrensy by the transfusion of
blood." Philosophical Trans., 1667, ii. 617.

72. DIEFFENBACH, J. F. : " Die Transfusion des Blutes

und die Infusion der Arzneien in Blutgefasse." Berlin,
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73. DIJK, H. VAN : " Malaria induced by convalescent's

serum." Nederl. Tijdschr. v. Geneesk., 1920, ii. 1181.

74. DORRANCE, G. M. : " Indications for blood transfusion."

Am. Journ. Med. Sci., 1917, cliv. 216.

75. DORRANCE, G. M., & GINSBURG, N. : " Transfusion :

history, development, present status and technique of
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76. DRINKER, C. R., & BRITTINGHAM, H. H. : " The

cause of the reactions following transfusion of citrated
blood." Arch. Int. Med., 1919, xxiii. 133.

77. DRUMMOND, H., & TAYLOR, E. S. : " The use of

intravenous injections of gum acacia in surgical shock."
Rep. of the Med. Res. Com., iii., 1919, 135.

" Observations on the blood pressure in gas gangrene
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78. DUKE, W. W. : " Variation in the platelet count."

Journ. Am. Med. Assoc, 1915, Ixv. 1600.

79. DUNGERN, E. VON, & HIRSCHFELD, L. : " Ueber

Nachweis und Vererbung biochemischer strukturen."
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viii. 526.

80. DUNGERN, E. VON, & HIRSCHFELD, L. : '' Ueber

Vererbung gruppenspezifischer strukturen des Blutes."
Ibid., 1910, vi. 284.

81. DUNGERN, E. VON, & HIRSCHFELD, L. : "Ueber

die Giftigkeit des Blutes nach der Injektion protoplas-
matischen Substanzen und wahrend der Schwangerschaft,
und iiber passive Allergic gegeniiber Hodensubstanzen."
' Ibid., 1911, viii. 332.

82. EBERLE, D. : " Transfusion and reinfusion of blood."

Schweiz. med. Wchnschr., 1920, 1. 961.

83. ELSBERG, C. A. : "A simple cannula for the direct

transfusion of blood." Journ. Am. Med. Assoc, 1909,
hi. 887.

84. ELY, A. H., & LINDEMAN, E. : " Acidosis complicating

r

BIBLIOGRAPHY 143

pregnancy. Report of a case cured by transfusion."
Am. Journ. Obstet. and Dis. Worn, and Child., July,
1916, Ixxiv. 42.

85. EMSHEIMER, H. W. : " Intramuscular injections of

whole blood in the treatment of purpura hsemorrhagica."
Journ. Am. Med. Assoc, 1916, Ixvi. 20.

86. EPSTEIN, A. A., & OTTENBERG, R. : ''A method

for agglutination tests." Arch. Int. Med., 1909, iii. 286.

87. ERLANGER, J., & GASSER, H. S. : " Hypertonic gum

acacia and glucose in the treatment of secondary trau-
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88. FLEMING, A., & PORTEOUS, A. B. : " Blood trans-

fusion by the citrate method." Lancet, 1919, i. 973.

89. FLORCKEN, H. : " Zur Frage der direkten Bluttrans-

fusion durch Gefassnaht." Zentrbl. f. Chir. Leipzic,
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90. FOLLI, FRANCESCO : " Stadera medica, nella quale

oltre la medicina infusoria, ed altre novita, si bilanciano
le ragioni favore voli e le contrarie alia trasfusione del
sangue." Florence, 1680.

91. FORSIUS, R. : " Severe haemophilic intestinal haemorrhage

treated with transfusion of blood." Finska Lakaresdll-
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92. FRANK, R. T., & BAEHR, G. : "A new method for the

transfusion of blood. An experimental study." Journ.
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93. ERASER, J., & COWELL, E. M. : ''A clinical study of the

blood pressure in wound conditions." Report of the
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94. FREILICH, E. B., and others : " Blood transfusion in

treatment of pulmonary tuberculosis." Illin. Med.
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95. FREUND, H. A. : "A method for the transfusion of fresh

normal blood." Journ. Michigan Med. Soc, 1913, xii. 459.

96. FRY, H. J. B. : " The use of immunized blood donors

in the treatment of pyogenic infections by whole blood
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97. FRYER, B. E. : "A few remarks on the transfusion of

blood, with a modification of the apparatus of Aveling."
Med. Rec, 1874, ix. 201.

144 BLOOD TRANSFUSION

98. FULLERTON, A., DREYER, G., & BAZETT, H. C. :

" Direct transfusion of blood, with a description of a
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99. GARB AT, A. L. : " Intravenous injections of sodium

citrate." Journ. Am. Med. Assoc., 1916, Ixvi. 1543.

100. GESELLIUS, F. : " Die Transfusion des Blutes." St.

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101. GESELLIUS, F. : " Zur Thierblut-Transfusion beim

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102. GETTLER, A. O., & LINDEMAN, E. : "A new method

of acidosis therapy. Blood transfusion from an alkali-
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103. GIFFIN, H. Z. : "A report on the treatment of pernicious

anaemia by transfusion and splenectomy." Journ.
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104. GRAHAM, J. M. : " Observations on the technique of

blood transfusion." Edin. Med. Journ., 1919, xxiii. 358.

105. GRAHAM, J. M. : " Transfusion of blood in cases of

haemorrhage." Edinb. Med. Journ., 1920, xxiv. 142.

106. GRAHAM, J. M. : " Transfusion of blood in pernicious

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107. GRUTZ, O, : " Bluttransfusion bei Morbus maculosus

Werlhofi." Berl. Klin. Wchnschr., 1921, Iviii. 53.

108. GUIOU, N. M. : " Blood transfusion in a field ambul-

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109. GURYE, G. DE : "An account of more tryals of trans-

fusion, accompanied with some considerations thereon,
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together with a farther vindication of this invention from
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110. HAHN, M. : " Haemophilia treated by transfusion."

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111. HALSTED, W. S. : " Refusion in the treatment of car-

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112. HAPP, W. M. : " Appearance of iso -agglutinins in infants

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Lancet, 1921, i. 737.

BIBLIOGRAPHY 145

114. HARRIS, D. T. : " The value of the vital-red method

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115. HARTWELL, J. A. : "A simple method of blood trans-

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116. HARTWELL, J. A. : "A consideration of the various

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117. HASSE, O. : " Report on twelve cases of the direct trans-

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118. HEDON, E. : " Note complementaire sur la transfusion

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121. HICKS, J. BRAXTON : " Cases of transfusion, with some

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122. HIGGINSON, A. : " Report of seven cases of transfusion

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123. HINDSE-NIELSEN : " Nitro-benzol poisoning treated

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124. HIRSCHFELD, L., & HIRSCHFELD, H. : " Serological

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125. HOFFMAN, M. H., & HABEIN, H. C. : " Transfusion of

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126. HOOKER, R. S. : " The treatment of staphylococcus

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10

146 BLOOD TRANSFUSION

127. HOWARD, W. S. : "A simple method of transfusion in

haemorrhage of the new-born, with report of a case.*'
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128. HUCK, F. G. : " Changes in the blood immediately follow-

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129. HULL, A. J. : " Direct transfusion of blood." Brit Med,

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130. HUNT, E. L., & INGLEBY, H. : '' A case of peptic ulcer

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131. HUNT, V. C. : " Reaction following blood transfusion by

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132. HUSTIN : " Principe d'une nouvelle methode de trans-

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133. HUTCHISON, R. : " Three cases of melsena neonatorum

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134. HUTER, C. : " Ein Fall von Kohlenoxydvergiftung ;

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135. INGEBRIGTSEN, R. : " The influence of iso-agglu-

tinins on the final results of homoplastic transplanta-
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136. JANEWAY, H. H. : " An improved device for trans-

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137. JANSKY, J. : " Haematologische Studien bei psykoti-

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138. JANSKY, J. : Recommendation by a committee that

the Jansky classification of blood groups be used in
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139. KAHN, A. : " Continuous transfusion. The production

of immunity." N.Y. Med. Rec, 1916, Ixxxix. 553.

140. KARSNER, H. T. : " Laboratory problems of blood

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141. KEATOR, H. M. : " Transfusion in case of toxaemia of

early pregnancy with unusual haemorrhagic manifesta-

BIBLIOGRAPHY 147

tions." Am. Journ. Obstet. and Dis. Worn, and Child,

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142. KEITH, N. M. : '' Blood volume changes in wound

shock and primary haemorrhage." Rep. of the Med.
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143. KEITH, N. M., ROWNTREE, L. G., & GERAGHTY,

J. T. : "A method for the determination of plasma and
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144. KEYNES, G. L. : " Blood transfusion ; its theory and

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145. KIMPTON, A. R., & BROWN, J. H. : "A new and

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146. KIMPTON, A. R. : " Further notes on transfusion by

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147. KIMPTON, A. R. : " Transfusion. Experiences in over

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148. KIMPTON, A. R., & BROWN, J. H. : " Technique of

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149. KING, E. : " An account of an easier and safer way of

transfusing blood out of one animal into another, viz.,
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150. KING, E. : " The method of transfusing into the veines

of men." Philosophical Trans., 1667, ii. 522.

151. KING, E. : " An account of the experiment of trans-

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152. KING, H. H. : " Direct vein to vein transfusion." Brit.

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153. KUSH, M. : " An automatic transfusion apparatus."

Journ. Am. Med. Assoc, 1915, Ixv. 1180.

154. LAMBERT, S. W. : " Melaena neonatorum, with report

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155. LANDOIS, L. : " Die Transfusion des Blutes." Berlin,

1866. Leipzig, 1875.

148 BLOOD TRANSFUSION

156. LANDSTEINER, K. : " Ueber Agglutinationserschei-

nungen normalen menschlichen Blutes." Wien. Klin.
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157. LAPAGE, C. P. : " Two cases of melsena neonatorum

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158. LAURIE, R. D. : " Melaena neonatorum treated by blood

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159. LEARMONTH, J. R. : " The inheritance of specific iso-

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160. LEE, R. I. : "A simple and rapid method for the selection

of suitable donors for transfusion by the determination
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161. LEISRINK, H. : "Ueber die Transfusion des Blutes."

Samm. Klin. Vortr., No. 41. Leipzig, 1872, 235.

162. LESPINASSE, V. D. : " The treatment of hsemorrhagic

disease of the new-born by direct transfusion of blood,
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163. LESPINASSE, V. D. : '' Technique of direct transfusion

of blood, using iridio-platinum tubes." Chicago Med.
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164. LESSER, L. : " Transfusion and autotransfusion."

Saniml. Klin. Vortr., No. 86, Leipzig, 1875. Inn. Med.,
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165. LEVIN, 1. : " Plastic surgery of blood vessels and direct

transfusion of blood." Ann. of Surg., N.Y., 1913, May.

166. LEWISOHN, R. : " A new and greatly simplified method

of blood transfusion." N.Y. Med. Rec, 1915, Ixxxvii.
141.

167. LEWISOHN, R. : " Blood transfusion by the citrate

method." Surg. Gynec and Obstet., 1915, xxi. 37.

168. LEWISOHN, R. : " The citrate method of blood trans-

fusion in children." Afn. Journ. Med. Sci., 1915, cl. 886.

169. LEWISOHN, R. : " The importance of the proper dosage

of sodium citrate in blood transfusion." Ann. of Surg.,
1916, Ixiv. 618.

170. LEWISOHN, R. : " Modern methods of blood trans-

fusion." Journ. Am. Med. Assoc, 1917, Ixviii. 826.

BIBLIOGRAPHY 149

171. LEYTON, O. : " Transfusion in diseases of the blood."

Brit. Med. Journ., 1919, i. 279.

172. LIBAVIUS, A. : " Denfensio syntagmatis arcanorum

chymicorum." Frankfort, 1615, eh. iv., p. 8.

173. LIBMAN, E., & OTTENBERG, R. : " A practical method

for determining the amount of blood passing over during
direct transfusion." Journ. Am. Med. Assoc, 1914,
Ixii. 764.

174. LIBMAN, E., & OTTENBERG, R. : " Recent observa-

tions on blood transfusion." Tr. Coll. Phys. Phila.,
1917, xxxix. 266.

175. LICHTENSTEIN : " Eigenbluttransfusion bei Extrau-

teringraviditat und Uterusruptur." Munch. Med.
Wchnschr., 1915, Ixii. 1597.

176. LINDEMAN, E. : " Simple syringe transfusion with

special cannulas." Am. Journ. Dis. of Childre7i, 1913,
vi. 28.

177. LINDEMAN, E. : " Blood transfusion. Report of one

hundred and thirty-five transfusions by the syringe-
cannula system." Journ. Am. Med. Assoc, 1914, Ixii.
993.

178. LINDEMAN, E. : " Reactions following blood transfu-

sion by the syringe cannula system." Journ. Am.
Med. Assoc, 1916, Ixvi. 624.

179. LINDEMAN, E. : " The total blood volume in per-

nicious anaemia." Journ. Am. Med. Assoc, 1918,
Ixx. 1292.

180. LITTLE, G. F. : " Transfusion of antibacterial blood.

Report of case." Journ. Am. Med. Assoc, 1920,
Ixxiv. 734.

181. LOSEE, J. R. : " Blood transfusion." Am. Journ. Med.

Sci., 1919, clviii. 711.

182. LOSEE, J. R. : " Blood transfusion in obstetrics." Med.

Rec, 1920, xcvii. 265.

183. LOWENTHAL, W. : " Ein Beitrag zur Lehre von der

Transfusion des Blutes." Berl. Klin. Wchnschr., 1871,
viii. 487.

184. LOWER, R. : " The method observed in transfusing the

blood out of one animal into another." Philosophical
Trans., 1666, i. 353.

150 BLOOD TRANSFUSION

185. McCLURE, R. D. : " Pernicious anaemia treated by

splenectomy, and systematic, often-repeated trans-
fusion of blood. Transfusion in benzol poisoning."
Journ. Am. Med. Assoc, 1916, Ixvii. 793.

186. McCLURE, R. D., ifc DUNN, G. R. : " Transfusion of

blood. History, methods, dangers, preliminary tests,
present status. Report of one hundred and fifty trans-
fusions." Johns Hopkins Hosp. Bull., 1917, xxviii. 99.

187. McGRATH, B. F. : "A simple instrument for [direct]

transfusion." Journ. Am. Med. Assoc, 1914, Ixii. 40.

188. McGRATH, B. F. : " Vascular suture in transfusion."

Journ. Am. Med. Assoc, 1914, Ixii. 1326.

189. McGRATH, B. F. : "A simple apparatus for transfusion

by the aspiration- injection method." Surg. Gynec
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190. MADGE, H. M. : " On transfusion of blood." Brit. Med.

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191. MANN, F. C. : " Experimental surgical shock. The

treatment of the condition of low blood pressure, which
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192. MARTIN : " Ueber cine mit gunstigem Erfolge bei einer

lebensgefahrlichem Intrauterinblutung vollzogeneTrans-
fusion." Monatschr. f. Gehurtsk. u. Frauenk., 1861,
xvii. 269.

193. MARTIN: " Iso- agglutination beimMenschen." Central-

blattf. Bact., 1905, xxxix. 704.

194. MELENEY, H. E., STEARNS, W. W., FORTUINE,

S. T., & FERRY, R. M. : " Post- transfusion reactions :
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195. MILLER, G. I. : " Blood transfusion, indications and

technique." Med. Rec, 1915, Ixxxviii. 425.

196. MINOT, G. R. : " Methods for testing donors for trans-

fusion of blood and consideration of factors influencing
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197. MINOT, G. R., & LEE, R. I. : " The blood platelets in

haemophilia." Arch. Int. Med., 1916, xviii. 474.

BIBLIOGRAPHY 151

198. MINOT, G. R., & LEE, R. I. : " Treatment of pernicious

anaemia, especially by transfusion and splenectomy."
Bost. Med. and Surg. Joiirn., 1917, clxxvii. 761.

199. MOREL, L. : " Transfusion of blood." Arch. gen. de

Chir., 1914, viii. 1.

200. MOSS, W. L. : " Studies on iso-agglutinins and iso-hemo-

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201. MOSS, W. L. : " Paroxysmal haemoglobinuria : blood

studies in three cases." Johns Hopkins Hosp. Bull.,
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202. MOSS, W. L. : "A simple method for the indirect trans-

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698.

203. MOSS, W. L. : "A simplified method for determining the

iso-agglutinin group in the selection of donors for blood
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1905.

204. NIX, J. T. : " Blood transfusion simplified. Deductions

from nineteen cases, eleven human and eight on dog."
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205. OEHLECKER, F. : " Bluttransfusion von Vene zu Vene

mit Messung der libertragenen Blutmenge." Zentralbl.
f. Chir., 1919, xlvi. 17.

206. OEHLECKER, F. : " Direkte Bluttransfusion von Vene

zu Vene bei perniziose Anaemic." Munchen. Med.
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207. ORE : " Etudes historiques et physiologiques sur la

transfusion du sang." Paris, 1868.

208. OTTENBERG, R. : " Transfusion and arterial anasto-

mosis." Ann. Surg., 1908, xlvii. 486.

209. OTTENBERG, R. : " Transfusion and the question of

intravascular agglutination." Journ. of Exp. Med.,
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210. OTTENBERG, R. : " The effect of sodium citrate on

blood coagulation in haemophilia." Proc. Soc. for Exp.
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211. OTTENBERG, R. : " Medico-legal applications of human

blood grouping." Journ. Am. Med. Assoc., 1921, Ixxvii.
682.

212. OTTENBERG, R., & FRIEDMAN, S, S, ; '' The occur-

152 BLOOD TRANSFUSION

- rence of grouped iso-agglutination in the lower animals."
Journ. Exp. Med., 1911, xiii. 531.

213. OTTENBERG, R., & KALISKI, D. J.: "Accidents in

transfusion. Their prevention by preliminary examina-
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Journ. Am. Med. Assoc, 1913, Ixi. 2138.

214. OTTENBERG, R., KALISKI, D. J., & FRIEDMAN,

S. S. : " Experimental agglutinative and hemolytic
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141.

215. OTTENBERG, R., & LIBMAN, E. : " Blood transfusion ;

indications ; results ; general management." Am.
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216. OTTENBERG, R., & THALIMER, W. : " Studies in

experimental transfusion." Journ. Med. Res., 1915-
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217. PANUM, P. L. : " Experimentelle Untersuchungen iiber

die Transfusion, Transplantation, oder Substitution des
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Virchow's Arch. f. Path. Anat, 1863, xxvii. 240, 433.

218. PEMBERTON, J. DE J. : " Blood transfusion." Surg.

Gynec. and Obstet, 1919, xxviii. 262. (Also in Collected
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219. PEMBERTON, J. DE J. : " Practical considerations of

the dangers associated with blood transfusions." Journ.
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Papers of the Mayo Clinic, 1919, xi. 635.)

220. PERCY, N. M. : "A simplified method of blood trans-

fusion, with report of six cases of pernicious anaemia
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Surg. Gynec. and Obstet., 1915, xxi. 360.

221. PETERSON, E. W. : " Purpura hsemorrhagica treated

by blood transfusion." Post-Graduate, N.Y., 1914,
xxix. 499.

222. PETERSON, E. W. : " Results from blood transfusion

in the treatment of severe post-operative anaemia and
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223. PETREN, G. : " Coagulation time in icterus." Beitr.

z. Klin. Chirurg., 1920, cxx. 501.

BIBLIOGRAPHY 153

224. PONFICK : " Experimentelle Beitrage zur Lehre von der

Transfusion." Virchow's Arch. f. Path. AnaL, 1875,
Ixii. 273.

225. POOL, E. H. : " Transfusion and splenectomy for von

Jaksch's anaemia in an infant." Ann. Surg., March
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226. POOL, E. H., & McCLURE, R. D. : " Transfusion by

Carrel's end-to-end suture method. With report of
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227. POPE, L. : " Simplified transfusion." Journ. Am. Med.

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228. PRIMROSE, A. : " The value of the transfusion of blood

in the treatment of the wounded in war." Ann. Surg.,
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229. PRIMROSE, A., & RYERSON, E. S. : " The direct

transfusion of blood, its value in haemorrhage and
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Brit. Med. Journ., 1916, ii. 384.

230. RAMIREZ, M. A.: ''Horse asthma following blood

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984.

231. RAMSAY, J. : " Transfusion of blood in nephritis."

Brit. Med. Journ., 1920, i. 766.

232. RANSOM, S. H. : " The treatment of staphylococcus

septicaemia by transfusion of immune blood." Ann,
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233. RAULSTON, B. O., & WOODYATT, R. T. : " Blood

transfusion in diabetes mellitus." Journ. Arn. Med.
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234. RICHARDSON, B. W. : " The cause of coagulation of

the blood. The Astley Cooper prize essay for 1856,
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235. RICHARDSON, E. H. : " Treatment of the emergency

cases of ectopic pregnancy." Johns Hopkins Hosp.
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236. ROBERTSON, L. B. : " The transfusion of whole blood."

Brit. Med. Journ., 1916, ii. 38.

237. ROBERTSON, L. B. : "A contribution on blood trans-

fusion in war surgery." Lancet, 1918, i. 759.

154 BLOOD TRANSFUSION

238. ROBERTSON, L. B. : " Blood transfusion in h^emorrhagic

disease of the new-born." Brit. Med. Journ., 1921, i.

239. ROBERTSON, L. B. : " Blood transfusion in severe

burns in infants and young children." Canad. Med.
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240. ROBERTSON, L. B., & WATSON, C. G. : " Further

observations on the results of blood transfusion in war
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241. ROBERTSON, O. H. : " The effects of experimental

plethora on blood production." Journ. Exper. Med.,
1917, xxvi. 221.

242. ROBERTSON, O. H. : "A method of citrated blood

transfusion." Brit. Med. J own., 1918, i. 477.

243. ROBERTSON, O. H. : " Transfusion with preserved red

cells." Brit. Med. Journ., 1918, i. 691.

244. ROBERTSON, O. H. : " Memorandum on blood trans-

fusion." Rep. of the Med. Res. Com., iv. 1919, 143.

245. ROBERTSON, O. H., & BOCK, A. V. : " Memorandum

on blood volume after haemorrhage." Rep. of the Med.
Res. Com., vi. 1919, 213.

246. ROBERTSON, O. H., & BOCK, A. V. : " Blood volume in

wounded soldiers." Journ. Exp. Med., 1919, xxix. 139.

247. ROSE, A. : "A case of melaena neonatorum successfully

treated by the injection of blood serum." Brit. Med.
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248. ROSE, C. W., & HUND, E. J. : '' Treatment of pneu-

monic disturbances complicating influenza." Journ.
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249. ROUS, P., & TURNER, J. R. : " The preservation of

living red blood cells in vitro. I. Methods of pre-
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250. ROUS, P., & WILSON, G. W. : " Fluid substitutes for

transfusion after haemorrhage." Journ. Am. Med.
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251. RUECK, G. A. : " Transfusion by the gravitation

method." Med. Rec, 1915, Ixxxvii. 354.

252. SALANT, W., & WISE, L. E. : " The action of sodium

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BIBLIOGRAPHY 155

253. SANFORD, A. H. : '' Iso-agglutination groups : a dia-

gram showing their interrelation." Journ. Am. Med.
Assoc, 1916, Ixvii. 808.

254. SANFORD, A. H. : " Selection of the donor for trans-

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255. SANFORD, A. H. : ''A modification of the Moss method

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256. SATTERLEE, H. S., & HOOKER, R. S. : " Experiments

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257. SATTERLEE, H. S., & HOOKER, R. S. : " The further

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258. SATTERLEE, H. S., & HOOKER, R. S. : " The use of

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259. SATTERLEE, H. S., & HOOKER, R. S. : " Transfusion

of blood, with special reference to the use of anti-
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260. SAUERBRUCH : " Artery of donor introduced directly

into recipient's vein for transfusion of blood." Munch.
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261. SCHEEL, O., & BANG, O. : " Transfusion in a case of

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262. SCHLOSS, C. M., & COMMINSKEY, L. J. J. : " Spon-

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263. SCHULTZ, W. : In Gravitz. " Klinische Pathologic des

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264. SCHWEITZER: "Blood reinfusion in extra-uterine

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699.

265. SIMONS, I. : " Experiences with the sodium citrate

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266. SHATTOCK, S. G. : " Chromocyte clumping in acute

pneumonia and certain other diseases, and the signific-

156 BLOOD TRANSFUSION

ance of the buffy coat in the shed blood." Journ. Path,
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267. SMITH, T. : " Transfusion of blood in the case of a

patient suffering from purpura." Lancet, 1873, i. 837.

268. SORESI, A. L. : " New instrument for direct transfusion

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269. SORESI, A. L. : " Clinical indications for direct trans-

fusion of blood, with the author's technique." Med.
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270. SPENCER, W. G. : " Transfusion of blood in civil

practice." Med. Sci. Abstr. and Rev., 1919, i. 309.

271. STANLEY, L. L. : "Blood transfusion apparatus."

Journ. Am. Med. Assoc, 1920, Ixxiv. 671.

272. STANSFELD, A. E. : " The principles of the transfusion

of blood." Lancet, 1917, i. 488.

273. STANSFELD, A. E. : " An apparatus for the transfusion

of blood by the citrate method." Laiicet, 1918, i. 334.

274. SYDENSTRICKER, V. P. W., MASON, V. R., &

RIVERS, T. M. : " Transfusion of blood by the citrate
method." Journ. Am. Med. Assoc, 1917, Ixviii. 1677.

275. TARR, E. M. : " Intravenous injections in infancy. Ad-

vantage of the superior longitudinal sinus route."
Arch. Pediatr., 1919, xxxvi. 71.

276. TELFER, S. V. : " Note on the preparation of sterile

gum acacia solution for intravenous injection." Rep.
of the Med. Res. Com., \., 1919, 42.

277. TERRIEN, E. : " Transfusion of blood in malignant

measles." Bull. Soc Med. des Hop., 1919, xliii. 1134.

278. THALIMER, W. : " Hemoglobinuria after a second

transfusion with the same donor." Journ. Am. Med.
Assoc, 1921, Ixxvi. 1345.

279. THOMAS, T. G. : " The intravenous injection of milk.

as a substitute for the transfusion of blood." N.Y.
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280. UNGER, L. : " Melsena neonatorum." Wien. Klin.

Woch., 1912, xxxix.

281. UNGER, L. J. : "A new method of syringe transfusion."

Journ. Am. Med. Assoc, 1915, Ixiv. 582.

282. UNGER, L. J. : " Recent simplifications of the syringe

BIBLIOGRAPHY 157

method of transfusion." Journ. Am. Med. Assoc. ^ 1915,
Ixv. 1029.

283. UNGER, L. J. : " Transfusion of unmodified blood, an

analysis of one hundred and sixty-five cases." Journ.
Am. Med. Assoc, 1917, Ixix. 2159.

284. UNGER, L. J. : " Precautions necessary in the selection

of a donor for blood transfusion." Journ. Am. Med.
Assoc, 1921, Ixxvi. 9.

285. VINCENT, B. : " Blood transfusion for hemorrhagic

diseases of the new-born. The use of the external
jugular vein in infants." Boston Med. and Surg. Journ.
1912, clxvi. 627.

286. VINCENT, B. : " Blood transfusion with paraffin-coated

needles and tubes." Surg. Gynec and Obstet., Nov.
1916.

287. VINES, H. W. C. : " Anaphylaxis in the treatment of

haemophilia." Quart. Journ. Med., 1920, xiii. 257.

288. VINES, H. W. C. : " The coagulation of the blood. I.

The role of calcium. II. The clotting complex."
Journ. Phys., 1921, Iv. 86, 287.

289. VOGEL, K. M., & McCURDY, U. F. : " Blood trans-

fusion and regeneration in pernicious anaemia." Arch.
Internat. Med., 1913, xii. 707.

290. WAAG, A. : " Repeated small injections of blood in per-

nicious anaemia." Munch. Medizin. Wchnschr., 1921,
Ixviii. 677.

291. WALLICH, V., & LEVADITI, C. : " Recherches sur

les reactions sanguines, a considerer a propos de la
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Ixxviii. No. 17.

292. WARD, G. : " Transfusion of plasma." Brit. Med.

Journ., 1918, i. 301.

293. WATSON, J. J. : "A method of fixation of vein to facili-

tate the introduction of a needle for intravenous injec-
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294. WAUGH, W. G. : " An investigation of the end result in

one hundred and twenty-four cases of blood trans-
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295. WEIL, P. E. : " Serum treatment of haemophiUa."

Lancet, 1920, ii. 300.

158 BLOOD TRANSFUSION

296. WEIL, R. J. : " Sodium citrate in the transfusion of

blood." Journ. Am. Med. Assoc, 1915, Ixiv. 425.

297. WILLIAMSON, H. : " Blood transfusion before opera-

tion in severe secondary anaemias." Lancet, 1920, i.
867.

298. WOLTMANN, H. : " Transfusion by the citrate method

in a sixty-hour-old baby with melsena neonatorum."
Am. Journ. Med. Set., 1915, Ixv. 2163.

299. WREN, SIR C. : " An account of the rise and attempts

of a way to conveigh liquors immediately into the mass
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300. ZIEMSSEN, VON : " Ueber die subcutane Blutinjection

und liber cine einfache Methode der intra venosen Trans-
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301. ZIMMERMANN, R. : " Blood transfusion in gyngeco-

logical cases." Miinch, Med. Wchnschr., 1920, Ixvii.
898.

302. ZIMMERMANN, R. : " Testing donor's blood before

transfusion." Zentralbl. f. Chir., Leipzig, 1920, xliv.
1146.

INDEX

Abdominal operations, shock in
relation to, 27
value of transfusion following, 32
Abdominal veins, " bleeding into,"

27
Accidents, loss of blood following, 20
Acholuric jaundice, blood condition
in, 93
blood groups of patients with, 93
transfusion in, 94
Acidosis, in pregnancy, 63
Agglutination, 84, 85
abnormal, 56
among animals, 79
in infants and children, 84
method of the test, 101
phenomenon of, 71-73
potential, of foetal corpuscles, 85
preceding haemolysis, 70, 76
Agglutinins, 71

in the blood, discovery of, 15
in maternal blood serum and

milk, 86
"major" and "minor," 73
" minor " in citrated blood, 123
" Agglutinophilic " properties of

blood corpuscles, 72, 85
Agote, Prof., first transfusion of

citrated blood by, 16
Air hunger, 21
Air-lock in transfusion apparatus,

125, 131, 133
Alkaline solution in treatment of

shock, 34
Alkalinized blood, 63
Amaurosis, 21
Amputations, value of transfusion

following, 32
Anaemia, 19, 50
acute, 19, 20

amount of blood necessary in

transfusion treatment, 25
effect of transfusion on, 22
following haemorrhage, 20, 24
signs and symptoms of, 20
transfusion treatment of, 31

Anaemia (contd. ) :
aplastic, 50
haemophilia with, 48
splenic, 50

see also Pernicious anaemia
Anaesthesia, transfusion in conjunc-
tion with, 33
Anaesthetics, shock accentuated by

administration of, 31
Anaphylactic shock, following trans-
fusion, 77
in pernicious anaemia, 57
influence on coagulation time of
blood, 45
Anastomosis, Crile's method, 109
for direct transfusion, 108, 109
Antecubital veins, injection of blood

into, 134, 135
Anti-agglutinins, 74
Antibodies, in the blood, 58
Anticoagulants, 16
action of, 120, 122
in haemophilia, 47
sodium citrate, 121
transfusion with, 118
Aplastic anaemia, 50
Arm tourniquet, 126, 128
Army, blood transfusion in, 17
Arteries, in direct transfusion, 108,
109
occlusion of, prevention of, 109
selection of, for transfusion, 108
Asthma, transmission of. 68
Auto-haemolysins, development of,

94
Auto-haemolysis of blood outside
the body, 94
phenomenon of, 94, 95

Bacteria, blood inhibiting growth

of, 58
Bacterial infections, 58-63

transfusion in relation to, 58, 60
Benzol poisoning, transfusion treat-
ment of, 65, 66

159

160

INDEX

Blood, administration of, apparatus
for, 115, 126, 127, 130-133
methods, 108, 112, 130-135
time occupied in, 131, 132
agglutinins and iso-agglutinins in,

15, 71, 72, 74
amount in the body, how mea-
sured, 22, 23
animals', use of, 5, 6, 8, 9, 15
anti-agglutinins in, 74
antibodies in, 58
auto-haemolysis of, 94
bactericidal power of, 58
calcium content of, 120
citrated, see Citrated blood
clotting of, see Coagulation
coagulation of, see Coagulation
defibrinated, early use of, 11, 12
examination of, for transfusion,

56, 57, 95
hydrogen-ion concentration of, 28
immunized, in pyogenic infec-
tions, 58
inhibiting growth of bacteria, 58
loss of, see Haemorrhage
maternal, agglutinins in, 86
of donors, see Blood donors
of patients, reinf usion with, 42, 43

testing of, 56
rapid administration, danger of,

78
substitutes for , 35, 36
testing of, for transfusion, 68, 83,

92, 95
total quantity in the body, 22
transfused, corpuscles in, 37
relative value of corpuscles
and plasma in, 36, 37
withdrawal of, methods and tech-
nique, 108, 112, 116, 126-128
Blood clot, mechanism of forma-
tion of, 119
rapid haemorrhage causing, 24
see also Coagulation
Blood corpuscles, "agglutinophilic"
properties of, 72, 85
and plasma, relative value of,

36, 37
clumping together of, 70
condition during shock, 39
conditions due to alterations in, 50
destruction of, in the toxaemias, 64
effect of transfusion on, 52
foBtal, potential agglutination of,

85
in transfused blood, 36, 37
function of, 37

Blood corpuscles {contd,):

quantity and concentration dur-
ing shock, 28
transfusion of, 64
Blood count, during shock, 39
following haemorrhage, 39
following transfusion, 40
in pernicious anaemia, 51, 53-56
Blood diseases, 50-58
Blood donor, 69
blood of, 56, 57

agglutinating power of serum

of, 72-74
testing of, 68

transmission of disease by, 67,
68
characteristics of, 100
choice of, 68, 96-107
effect of blood loss on, 99
for new-born infants, 49
for pernicious anaemia, 56, 57
injury to, during transfusion. 111,

124
members of patient's familv as,

85, 90, 92, 95
" professional," 69, 98
testing of, 83, 92, 95-97
for blood groups, 101
treatment of, 60, 99, 100
" universal," 72, 73
vaccine treatment of, prior to

withdrawal of blood, 60
withdrawal of blood from, 108,
109, 124
by anastomosis, 108, 109
by Kimpton-Brown tube, 116,

117
by needle, 126-128
by syringe, 112, 113
Blood groups, 67, 69, 70, 101
among animals, 79
and disease, relation between,

81, 93
classification of, 70, 71
compatibility of, 72, 75, 80
in families, 84, 90, 92
testing of, 102
earliest classification of, 15
family incidence of, 84, 90, 92
incidence among our own popula-
tion, 83
incompatibility of, 80, 92
earliest reference to, 6
in animals, 80
in families, 84, 90, 92
symptoms of, 75-77
testing for, 101, 102

INDEX

161

Blood groups {contd.) :

inheritance of, 86, 87, 90, 91

medico-legal considerations, 92
maternal, compared with those of

infants, 86, 92
overlapping of, 72, 96
pathology of, 79
phenomena of, 69-75
physiology of, 79
popular beliefs concerning, 84
racial incidence of, 81, 82
reactions between the serum and

corpuscles of, 70, 71, 72, 73
testing for, in blood donors, 97,

101
transfusion in relation to, 95
" unit characters " in, 86, 87, 88
Blood measurements, 22, 23
Blood plasma, in transfused blood,

36, 37
Blood pressure, 21

as an indication for transfusion,

40
danger points in, 21
following loss of blood, 21
low, essential feature of shock, 27
transfusion treatment of, 32
Blood reactions, 70, 71, 72, 80, 101
clinical pictiire of, 75
disease in relation to, 93
family incidence of, 84, 90, 92,

95
following transfusion, 95, 96, 122,

123
in infants, 84, 90, 92
incompatibility of, transfusion in

relation to, 96
intensity of, variations in, 73
recognition of symptoms of, 75-

77
variation in degree of, 76
Blood recipients, " universal," 72,

95
" Blood relations," transfusion in

relation to, 84, 92, 95
Blood serum, agglutination test of,
101
preservation of , 101, 102
stock, 101

collection of, 102
Blood volume, changes in, in haemor-
rhage and shock, 24, 25, 27
diminution in shock, 27, 32
estimation of, 22
imperfect oxygenation due to,
36
life dependent on, 24, 25

11

Blundell, James, his " impellor,"
10, 11
transfusion by (in 1818), 10, 11

Body, total quantity of blood in the,
22

Breathing, difficult, during trans-
fusion, 78

Burns, transfusion for shock due to,
136

Calcium, action of, 120

in the blood, forms in which pre-
sent, 120
precipitation of, 119
Cancer, transfusion for, 9, 18
Cannula, for direct transfusion, 110

for indirect transfusion, 130
Capillary circulation, condition
during shock, 39
stagnation of, following
haemorrhage and shock, 27,
29
Carbon monoxide poisoning, 64
condition of the blood in, 64
transfusion treatment of, 64, 65
Children, transfusion of, technique,
134
see also Infants
Chloroform, shock accentuated by

administration of, 31
Chlorosis, 50

Circulation, blood volume necessary
to maintain balance of, 24,
25
capillary and venous, comparison

during shock, 39
condition during shock and

haemorrhage, 27, 28, 29, 39
stagnation of, 28
see also Blood
Citrate reactions, 122, 123
Citrated blood, 16, 121, 124

administration of, methods, 129-

134
keeping and care of, 128, 129
reaction following use of , 122, 123
transfusion of, 121, 124
first recorded case of, 16
in pernicious anaemia, 51, 56
see also Sodium citrate
Clotting, see Coagulation
Coagulation, deficient, following
haemorrhage, 41
fficulties connected with, in
early experiments, 11, 12
effect of transfusion on, 42

162

INDEX

Coagulation, mechanism of produc-
tion of, 119
outside the body, 118, 119
prevention of, 114, 120
Clotting, prevention of, by sodium
citrate, 119, 120
prevention of, during transfusion,

109, 110, 112
transfusion simplified by pre-
vention of, 119
Coagulation time, anaphylactic
shock influencing, 45
effect of transfusion on, 46, 47
haemorrhage in relation to, 44, 45
in jaundice, 44
prolongation of, 44
Coal-gas poisoning, transfusion

treatment of, 64
Coga, Arthur, 8

Cold, predisposing to shock, 29, 30
Cox, Thomas, transfusion experi-
ments by, 3
Crile, improvement in technique of
transfusion by, 15
method of direct transfusion, 109
Curtis and David, improvements
in technique of transfusion
by, 16

Daniel, of Leipsic, 3
Darwin, Erasmus, 9
Death, loss of blood causing, 24
Denys, John, first human trans-
fusion performed by, 3, 5, 6
Diabetes mellitus, transfusion in,

66
Diphtheria, 60

acute toxaemia in, 60
experimental transfusion in, 60,
61
Direct transfusion, apparatus for,
109, 110
methods, 108, 109, 110
objections to, 110, 111
technique of, 108-111
Disease, relation between blood
groups and, 81, 93
transmission by blood trans-
fusion, 68
Drysdale, Dr. J. H., 52
Duodenal ulcer, severe haemorrhage
from, transfusion treatment,
41

Eclampsia, "foetal threat" in re-
lation to, 85
transfusion treatment, 62

Ectopic gestation, rupture of, trans-
fusion following, 42

Elsberg and Bernheim's method of
direct transfusion, 109

Emboli, multiple, 77

Endocarditis, transfusion for, 60

Ether, shock accentuated by ad-
ministration of, 31

Fever, transfusion for, 9

Fluids, administration of, during
shock, 34

" Foetal threat," 85

Folli, Francesco, supposed blood
transfusion by (1654), 2

Fontanelle, use of, 135, 136

Forced fluids, 34

Fullerton's method of direct trans-
fusion, 110

Gametes, segregation of, 88
Gastric ulcer, severe haemorrhage
from, transfusion treatment,
41
Grafts, tissue, 80
Gum transfusion, 35, 36, 37

and blood transfusion, relative

value of, 35, 37
objections to, 36
Gurye, Caspar de, 6

Haematemesis, treatment of, 41
Haemoglobin percentage, during

shock and haemorrhage, 39
Haemoglobinuria, 6, 7, 70

as symptom of blood reaction, 76

following blood transfusion, 76

paroxysmal,blood condition in, 94
Haemolysed blood, toxicity of, 77
Haemolysins, 71
Haemolysis, 94, 95

agglutination preceding, 70, 76

early reference to, 6
Haemophilia, anaemia with, 48

anticoagulants in, 47

blood condition in, 45

sodium citrate administration in,
47, 48

transfusion treatment of, 45-48
Haemophilics, coagulation time of
blood of, 46, 47

transfusion beneficial to, 46
Haemorrhage, 20

acute anaemia following, 20, 24

blood counts following, 39
• blood- volume changes in, 24, 25,
27

INDEX

163

Haemorrhage, coagulation time in
relation to, 44, 45
condition of blood following, 24,

27, 28, 39
danger of, 20, 23
effects of, how combated, 33
following gastric or duodenal
ulcer, transfusion treatment,
41
general treatment of, 31, 33
gum treatment of, 35, 36
in new-born infants, transfusion

treatment, 49
intraperitoneal, 42
limits of, 24

post-partum, transfusion treat-
ment, 42
rapid, 23, 24

reflex compensation for, 99
reinfusion treatment of, 42
saline treatment of, 33
secondary, 40, 41

indications for transfusion in, 41
shock always associated with, 20,

26
shock and, clinical difference be-
tween, 38
signs and symptoms of, 38
transfusion treatment of , 20, 25,31
effects of, how judged, 40
indications for, 40
traumatic, 40
Haemorrhagic diseases, 44-50
Haemostasis, blood transfusion pro-
ducing, 42, 44, 45, 48
Harvey, William, his theory of the

circulation, 2
Heart, dilatation of, 78

effect of loss of blood on, 23
Helmholtz, method of transfusion

of infants, 135
Heredity, blood groups in relation
to, 86, 87, 90, 91
Mendelian theory of, 86, 90
Higginson's transfusion instrument,

13, 14
Hirudin, use of, 16
Histamine, 30
production of, 30
production of shock by, 30
Horse asthma, transmission of, 68
Howard's method of transfusion

of infants, 135
Hydrogen-ion concentration in the
blood, 28, 31
shock in relation to, 28, 32
Hydrophobia, transfusion for, 9

Immunized blood, transfusion by,

in pyogenic infections, 58
Incompatibility, symptoms of, 6, 75
Indirect transfusion. 111
Infants, blood groups in, 84, 92

compared with those of
mothers, 86, 92
blood reactions in, 84, 90, 92
transfusion of, 48

conditions necessitating, 49,

134
dosage, 136
technique, 134-136
with maternal blood, 85, 92
withdrawal of blood from, 136
Influenzal pneumonia, transfusion

for, 61
Innocent VIII, 2

Internal saphenous vein, injection
of blood into, in infants, 136
Iso-agglutinins, 72, 79

distribution among animals, 79,
80
Iso-haemolysins, 72, 79

in animals, artificial reproduction
of, 96
Isotonic saline solution in treat-
ment of shock, 34

Jaiuidice, 44

acholuric, transfusion in, 94
blood groups in patients with,

93
haemorrhage following operation

in cases of, 44
transfusion in cases of, 44
Joekes, Dr., 52, 57
Jugular vein, injection of blood
into, 135

Keith, on blood volimie changes,
24, 27
on shock and haemorrhage, 32

Kimpton and Brown, improve-
ments in technique of trans-
fusion by, 16

Kimpton-Brown tube, whole blood
transfusion with, technique,
114

King, Edmund, transfusion experi-
ments by, 3, 4, 8

Lamb's blood, early transfusions

with, 5, 9, 15
Legitimacy, inheritance of blood

groups in relation to, 92

164

INDEX

Leuksemia, 50

blood groups in patients suffering
from, 81

Lewisohn's sodium citrate experi-
ments, 16, 120, 122, 123

Longitudinal sinus, use of, 135

Lower, Richard, transfusion ex-
periments by, 3, 8

Malaria, transmission by trans-
fusion, 67, 68
Malignant disease, blood groups in
patients suffering from, 81,
93
" Maternal threat," 85, 92
Measles, blood injections in, 62
Median basilic vein, accessible for
direct transfusion, 108
incision of, 130
puncture of, 126-128
Melsena neonatorum, transfusion
for, technique, 134, 135
value of transfusion in, 48
Mendelian theory, 86, 90

of blood groups, 86, 87, 88, 90
Milk, injection of, 15

maternal, agglutinins in, 86
Muscle, damaged, production of
histamine from, 30

Needle, for transfusion, 126
case of, 126
improved form of, 113
Nephritis, transfusion treatment of,

63
New-born infants, blood donors for,
49
blood reactions of, 84, 90, 92
hsemorrhagic disease of, 48, 49
transfusion of, 48
technique, 134-136
with maternal blood, 84, 85, 92
Nitrobenzol poisoning, transfusion
treatment of, 65

Obstetrics, transfusion in, 42
Operations, shock following, 31

value of transfusion following, 32
Osmotic pressure, 36
significance of, 36
Oxygenation, imperfect, blood loss
causing, 36
solutions increasing, 37
Oxyhsemoglobin, conversion into
carboxyhsemoglobin in car-
bon monoxide poisoning, 64

Pain, predisposing to shock, 29
Paraffin wax, coating of glass tube
with, 114, 116
in prevention of clotting, 110, 1 14
Paroxysmal hsemoglobinuria, blood

conditions in, 94
Pedigree of blood groups, 90
Pellagra, transfusion in cases of, 66
Pepys, Samuel, 7, 8, 9
Pernicious anaemia, 50
blood condition in, 93
blood count in, 51, 53-56
blood groups in patients with, 93
subcutaneous blood injections in,

58
transfusion treatment of, 50-58,
95
complications of, 57
cases illustrating, 53-55
choice of blood donor, 56, 57
dosage, 52

reactions following, 57
Perspiration, blood loss due to, 28
Placenta prsevia, transfusion follow-
ing, 42
Pneumonia, transfusion in cases of,

61
Poisoning, transfusion treatment of,

64, 65
Post-operative shock, 31
Post-partum haemorrhage, 42
Pregnancy, toxaemias, of " foetal
threat " in relation to, 85
transfusion treatment of, 62
" Professional " blood donor, 69, 98
Purpxira, transfusion in cases of,

49, 50
Pyaemia, transfusion in cases of, 59
transfusion in, 58

Radial artery, accessible for direct
transfusion, 109
exposure of. 111
objections to use of. 111
Reactions, 75, 76

following transfusions, 57, 122, 123
see also Blood reactions
Reinfusion with patient's own

blood, 42, 43
Rejuvenation, 136
Replacement of blood, complete, 136
Respiratory system, effect of loss of
blood on, 23
exhaustion of, 21
Robertson, Bruce, transfusion of
infants and children by, 135,
136

INDEX

165

Robertson, Oswald, transfusion
with citrated blood by, 121,
124

" Robertson's bottle," 124, 125

Valine infusion, treatment of shock

by, 33
Saphenous vein, internal use of, 1 30,

135
Sauerbruch's method of direct

transfusion, 108
Segregation of the gametes, 88
Septicaemia, transfusion for, 59, 136
Serum, see Blood serum
Shock, 20

abdominal operations in relation

to, 27
alkaline administration during,

34
anaphylactic, see Anaphylactic

shock
avoidance of, following haemor-
rhage, 29
blood count during, 39
blood volimie changes in, 24, 25,

27, 32
capillary system during, 27, 28,

29
causal theories of, 26, 27
conditions of the blood during,

24, 27, 28, 39
effects of, how combated, 33
experimental production of, 30
fluid administration during, 34
gum treatment of, 35, 36
haemorrhage always associated

with, 26
haemorrhage and, differential

diagnosis, 38, 39
hydrogen-ion concentration in

relation to, 28, 32
low blood pressure the essential

feature of, 27
mechanism of production of, 30
post-operative, 31
primary, 29

reinfusion treatment, 42
saline treatment of, 33
secondary, 29

conditions predisposing to, 29
signs and symptoms of, 26, 29, 38
theories regarding, 26
toxic theory of, 30
transfusion treatment of, 20, 26,
31
indications for, 40

Skin eruption, as symptoms of

blood reaction, 76, 77
Sodium bicarbonate, in treatment

of shock, 34
Sodium citrate, absorption and
elimination of, 120
action of, 122

as an anticoagulant, 16, 121
coagulation time of the blood re-
duced by, 47
dosage, 121, 122
elimination of, 120
form in which used, 123
in haemophilia, 47
in prevention of clotting, 119,

120
reactions following use of, 122,

123
tolerance to, 122
toxicity of, 77
Sodium phosphate, use of, 16
Solutions, for transfusion, essential
constituents of, 36, 37
viscosity and osmotic pressure of,
36
Spinal anaesthesia, transfusion in

conjunction with, 33
Splenic anaemia, 50
Stansf eld's apparatus, 134
Staphylococcal septicaemia, blood

transfusion in, 59, 60
Sterility and blood groups, 80
Streptococcal septicaemia, blood

transfusion in, 136
Syphilis, transmission by blood

transfusion, 68
Syringe, cleansing of, 114
Higginson's, 13, 14
whole blood transfusion with,
technique, 112-114

Tissue transplantation, success of,
dependent upon compatibi-
lity of blood groups, 80
Tissues, damage to, producing toxic

substances, 30
Tourniquet, Canti's, 126, 128
Toxaemia, 58-66

acute, in bacterial diseases, 60
blood transfusion in, 31, 58, 60,

61
of pregnancy, transfusion treat-
ment of, 62
traumatic, 30-32
production of, 30
Toxic theory of shock, 30

166

INDEX

Transfusion, apparatus for, 115,126,
127, 130-133
in early experiments, 10, 13
recent improvements in, 15
continuous, 60

direct method, technique, 108-1 1 1
early objections to, 9
history of, 1

ideal method of, 124, 132
indirect method, technique, 111-

112
of infants, 134

technique, 134
recent advances in knowledge and

technique of, 15-17
repeated, 57

Robertson's citrate method, 121,
124
apparatus for, 124, 134
whole blood, with syringes, tech-
nique, 112
with anticoagulants, technique,

118-134
with Kimpton-Brown tube, 114
Traumatic toxaemia, 30-32
Tuberciilosis, transfusion in, 62
Twins, blood groups in, 92
Typhoid, transfusion in, 62

" Universal donors," 72, 73
" Universal recipients," 72
Urine, haemoglobin in, 39, 70, 76

suppression of, 76, 77
Urticaria, following transfusion, 77
Uterus, rupture of, 42

Vaccine, injection of, into blood

donors, 59, 60
Vaso-motor failure, in shock, 26
Vein, for direct transfusion, 108,
109
injection of blood into, 134, 135
insertion of cannula in, 131
occlusion of, prevention of, 109
puncture of, 113

technique, 126-128
prevention of injury to, 113, 124
Venesection, preceding transfusion,
60
in carbon monoxide poisoning,
65
Venospasm, 27

Venous circulation, condition dur-
ing shock, 39
Viscosity, 36

significance of, 36
Vital red, use of, 23

War, transfusion in, 17
Water, during severe shock, 34
Whole blood transfusion, apparatus
for, 114
objections to, 118
prevention of clotting, 114, 118
with Kimpton-Brown tube, tech-
nique, 114-118
with syringes, 112-114
Willis, Thomas, 3
" Woimd shock," 29
Wren, Sir Christopher, vein injec-
tions by, 2, 3

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