INDICATIONS FOR BLOOD TRANSFUSION--_continued_
HÆMORRHAGIC DISEASES
It is claimed that blood transfusion provides an efficient means of
treatment in most conditions distinguished by symptoms of spontaneous
hæmorrhage or by traumatic hæmorrhage 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
hæmostasis. 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
found to be more effective than transfusion, though the intravenous
administration of calcium compounds is sometimes of value.
=Hæmophilia.=--Blood transfusion is of still greater value when the
coagulation time of the blood is prolonged owing to a congenital
deficiency, as in hæmophilia. It is unnecessary 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 hæmophilic 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 hæmophilia
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 blood supplies directly the deficient
factor in the coagulation 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 anæmia. 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 transfusion 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
transfused 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 hæmophilic 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 coagulation time
of the blood rests upon the evidence of a number of independent
observers. Pemberton has recorded a case of a hæmophilic 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.
Other observations have been made as follows:
-------------+-----------------------------+----------
| Coagulation time. | Minutes.
-------------+-----------------------------+----------
Bulger | Before transfusion | 82
| 1 day after transfusion | 10
| 8 days ” ” | 8
| 25 ” ” ” | 40
-------------+-----------------------------+----------
Minot & Lee | Before transfusion | 150
| After ” | normal
| 3 days after transfusion | 60
| 5 ” ” ” | 100
-------------+-----------------------------+----------
Addis | Before transfusion | 245
| After ” | 24
| 25 days after transfusion | 200
| After 8 cc. serum injected | 38
-------------+-----------------------------+----------
In treating jaundice or hæmophilia 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 hæmostatic 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 hæmostatic 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 hæmophilic, 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 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 hæmophilia than untreated
blood.
The amount of blood to be transfused in hæmophilia will vary with
the age of the patient and according to whether he is suffering from
acute anæmia or not. If hæmostatic effects only are wanted, 100 cc.
of blood will be enough. If anæmia is also present, the dosage will
be governed by the same considerations as have already been discussed
in the section on the treatment of hæmorrhage.
=Melæna Neonatorum.=--Another hæmorrhagic condition in which blood
transfusion is of the very greatest value is that known as _melæna
neonatorum_. Severe hæmorrhage 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 hæmostasis is usually brought
about by blood transfusion. Horse serum has often been successfully
used as in treating hæmophilia, but blood transfusion again has
the additional merit that the blood which has been lost is thereby
replaced. A single transfusion is usually enough, as the hæmorrhage
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 transfusion 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 _melæna neonatorum_ has not been very
generally recognized, but a number of striking 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 moribund, 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 hæmorrhagic disease of the new-born which were treated
by transfusion, all recovered except four; of these two died from
associated umbilical sepsis, one from intracranial hæmorrhage, 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 hæmorrhagic diseases, the two already
described, hæmophilia and melæna neonatorum, are the only ones for
which blood transfusion is a really effective remedy. It is probable
that under the somewhat general term “purpura hæmorrhagica” are
grouped several conditions, all of very obscure origin, none of
which are conspicuously benefited by transfusion. Many transfusions
have been given for purpuric symptoms, chiefly in America. Several
cases are reported by Bernheim, 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 benefited 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 transfusion, 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 Anæmia.=--Blood transfusion has been advocated for
several conditions characterized by alterations in the cells of
the patient’s blood. It has been used in the treatment of aplastic
anæmia, splenic anæmia, chlorosis, and leukæmia, but in none of these
diseases has it been of much avail. In pernicious anæmia, 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 anæmia from some forms of secondary
anæmia. It is hardly to be expected that much benefit would follow
blood transfusion in the undiagnosed secondary type, since the
destruction or loss of corpuscles is continuous until the cause has
been removed. In true pernicious anæmia, 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
anæmia 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 dyspnœic, semi-conscious, and moribund
when admitted to hospital. His red cells numbered 850,000 per cmm.,
and his hæmoglobin percentage was 19. Immediate improvement followed
the transfusion of 900 cc. of citrated 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. Probably 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 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 anæmia 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
transfusions 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 treatment 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 hæmopoietic 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 unknown, 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.
[Illustration: Fig. 3.--PERNICIOUS ANÆMIA, CASE I]
I. A woman, aged 51, had been treated for four years for pernicious
anæmia, and when admitted to hospital was becoming steadily worse.
The red corpuscles numbered 1,470,000 per cmm., and her hæmoglobin
percentage was 32 on October 21, 1918, and by November 19 they had
fallen to 750,000 and 25. On November 22 she was transfused with 500
cc. of citrated blood, and a blood count made immediately afterwards
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 January 28 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 hæmoglobin 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 which follows the initial rise. The diagram shows the
results more graphically.
[Illustration: Fig. 4.--PERNICIOUS ANÆMIA, CASE II]
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 from 1,250,000 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 continued steadily, and
three months later her blood count was 3,690,000 per cmm. Two very
small additional transfusions 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.
[Illustration: Fig. 5.--PERNICIOUS ANÆMIA, CASE III]
III. A less favourable result is illustrated by the following
history: A stores assistant, aged 47, had been ill for two years,
and was first treated for pernicious anæmia in 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
transfused 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 numbered 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 improvement 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 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
anæmia, 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
anæmia, 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; nevertheless, 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 anæmia. 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. Nevertheless,
the patient’s serum strongly agglutinated the corpuscles of both of
them, so that I considered it inadvisable 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 anæmia 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 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 anæmia, but in
reality indicates that there is another underlying cause for the
anæmia, 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
investigation. 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 beforehand 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 anæmia 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 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.
TOXÆMIAS
_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 transfusion of
immunized blood.
This method has at present not progressed beyond the stage of
preliminary trials. I have attempted it in one case, but without any
obvious benefit. The patient was a middle-aged man suffering from a
chronic staphylococcal septicæmia and a secondary anæmia. 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 underwent a temporary 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 staphylococcal (one)
septicæmia, 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. Improvement
definitely followed the transfusions, and his recovery was afterwards
encouraged by injections of an autogenous vaccine. The other five
patients received similar treatment, but all died. The remaining
three patients had chronic suppuration, one following a streptococcal
arthritis of the knee, but no septicæmia, 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 pyæmia 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 septicæmia by
correcting the anæmia 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 venesection
before transfusion. A striking case of staphylococcal septicæmia 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 transfusion 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 infection 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
toxæmia, 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 toxæmic stage was found to occur on the fourth
to the eleventh day. It was characterized 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 to trauma or to hæmorrhage, and it was shown by experiment that
the treatment must be directed towards increasing 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, recommended for the treatment of children in the toxæmia
stage of diphtheria:
--------------+-----------+-----------
Age. | Weight. | Amount.
--------------+-----------+-----------
1½ years. | 21 lbs. | 160 ccm.
2 ” | 28 ” | 200 ”
4 ” | 35 ” | 300 ”
6 ” | 42 ” | 400 ”
--------------+-----------+-----------
=Pneumonia.=--A condition of toxæmia 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 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 varying 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 hæmorrhage in typhoid,
but this is chiefly with the object of combating anæmia. 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 complement 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.
=Toxæmias 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
symptoms 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 individuals. 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 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 toxæmia
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
treatment.
=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 admission 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 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 oxyhæmoglobin has been converted into
carboxyhæmoglobin, 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 carboxyhæmoglobin is dissociated and replaced by oxyhæmoglobin.
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 Hüter 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 Brunton 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. 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 transfusion 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 minimum amount of 750 cc. of blood should be taken by
venesection, and 1,000 cc. of blood should be given. If the patient’s
condition does not then show enough improvement, this should be
repeated.
=Nitrobenzol and Benzol Poisoning.=--Blood transfusion for poisoning
with nitro-benzol (C_{6}H_{5}NO_{2}) 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 inhalation 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, oxyhæmoglobin being in this case replaced by
methhæmoglobin, and its treatment by transfusion has, therefore, a
rational basis.
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
transfused by Raulston was actually made worse, as was indicated by
an increased output of sugar, acetone, and ammonia compounds.
=Pellagra.=--The precise ætiology 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 transfused blood provides a
temporary supply of the substance that is lacking; the patient is
thus enabled to start along the road to recovery.