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-hæmolysins, 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 distribution of
iso-agglutinins among animals were made by Hektoen 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 insufficient 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 Dungern has 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 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 transplantation 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
compatibility of blood groups in donor and recipient. The problem
is one that cannot easily be investigated by experiment 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-hæmolysins
were seldom if ever found in normal cats, though they often
appeared in the recipients of transfusions. Grafting experiments
might therefore be preceded by transfusions designed to stimulate
artificially incompatibility 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 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 leukæmia, 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 afterwards converged and mingled, with the production
of serological hybrids. In view of this it is 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 approximately 8,000
individuals, including French, English, Italians, Germans, Austrians,
Serbs, Greeks, Bulgarians, 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 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 percentages 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 compatibility 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 misapprehensions 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 sometimes 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 untested 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 indicating 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 percentage 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 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 afterwards 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 fœtal corpuscles by the mother’s
serum, and of the maternal corpuscles by the serum of the fœtus, the
“maternal threat” and the “fœtal threat” respectively, and states
that there is no obvious relationship between the “fœtal threat” and
eclampsia or the toxæmias of pregnancy. The inference is therefore
justified that there is no transference of the agglutinating
substances in either direction across the placental membranes. No
chemical “immunity” is acquired, therefore, on either side, since
the protection is mechanical. This agrees with the fact observed
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 therefore 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 of 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 satisfactorily 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 “dominant” 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 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 conventional 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 consideration, 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 producing 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 individuals of Group II. It includes not only the
agglutinin or hæmolysin of the serum which reacts with corpuscles of
Group III, but also the complementary iso-agglutinin or iso-hæmolysin
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
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 union may again be
constituted in three ways--BB, Bb, or bb.
In computing the results, however, it must be remembered 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 which blood groups
result from which combinations, if it be remembered that
A is dominant to a,
B ” ” ” b,
and that
Group I results from the _presence_ of both A and B.
” II ” ” ” ” ” A only.
” III ” ” ” ” ” B ”
” 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.
Ab--ab.
” III ” ” ” ” ab--aB.
aB--aB.
” IV ” ” ” ” ab--ab.
It now becomes evident what offspring may result from the union of
parents who have any of the above constitutions. Thus parents both of
Group I may have offspring belonging to any group according to which
of the five possible constitutions they possess. If the union be
represented by
AB--AB × 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 × II, I × III, or II × 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
offspring. Thus II × II or II × IV can only produce Groups II or IV;
III × III or III × IV can only produce Groups III or IV; IV × 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 account of it the
reader must be referred to the standard works on the subject.[6]
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 published 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 observations were inaccurate, and we
are therefore brought to the conclusion that in such a case the child
is illegitimate.
[Illustration: Fig. 6.--PEDIGREE SHOWING INHERITANCE OF BLOOD GROUPS
THROUGH FOUR GENERATIONS. THE GROUP OF EACH INDIVIDUAL IS INDICATED
BY A NUMERAL. THOSE WHO WERE NOT AVAILABLE ARE REPRESENTED BY A O]
The conclusions which emerge from this structure of theory and fact
are obviously of very great clinical importance. It is now clearly
demonstrated that a mother belonging, say, to Group I, may give
birth to a child belonging 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 agglutination reactions of
the blood and serum. It has already been mentioned that there is no
proof that the possession of any 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 alteration in the reactions of
the blood of these patients. It is probable, indeed, that evidence of
this alteration in malignant disease already exists, for a reference
to it is to be found in Kolmer’s work on serum-therapy,[7] 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 anæmia 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 therefore nominally belonged to Group II. His serum,
however, when separated and tested against other bloods of known
groups gave, in addition to a rapid agglutination of corpuscles
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-hæmolysis. 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 hæmoglobin, even though it
has remained absolutely sterile. It appears, therefore, that the
serum develops a hæmolysin and the corpuscles the corresponding
iso-hæmolysin, 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 hæmoglobinuria. The pathology of the disease is
obscure, but it seems that a hæmolysin develops in the serum as the
result of cooling in the extremities and hæmolysis takes place when
the cooled serum is again warmed by being restored to the general
circulation. The presence of this hæmolysin in addition to the normal
hæmolysins has been demonstrated by Moss. It is possible that a
similar though less acute change takes place in acholuric jaundice.
Blood transfusion, 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-hæmolysis have been recently investigated by Bond, but it is not
necessary to give the details here. He concludes that the development
of auto-hæmolysins, which are non-specific and independent of
the specific hæmolysins of the blood groups, has a 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 anæmia. In such cases, although the groups were
ascertained, and the bloods were also tested directly against one
another without any incompatibility being detected, yet when the
third or fourth transfusion was given, symptoms of toxæmia followed,
sometimes with hæmolysis. 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 pronounced hæmoglobinuria. 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 ascertained 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 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 consequently
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-hæmolysins in cats. In these animals iso-agglutinins are
found, but iso-hæmolysins seldom or never. The reaction is, however,
found to become hæmolytic 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 incompatibilities 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 sensitization
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.