TRANSFUSION THERAPY OF ACUTE HEMOLYTIC ANEMIA OF THE
NEWBORN*
A. S. WIENER AND I. B. WEXLER
From the Division of Blood Transfusion of the Department of Laboratories and the
Department of Pediatrics of the Jewish Hospital of Brooklyn
The first step in arriving at an understanding of acute hemolytic anémia of the
newborn was made by Diamond, Blackfan and Baty 1 who showed that erythroblastosis fetalis, fetal hydrops, icterus gravis neonatorum and congénital
anémia of the newborn ail hâve similar pathologie changes. The pathogenesis
of the disease was not clearly understood until 1941 when Levine et al.2 • 3 demonstrated the rôle of the Rh factor of Landsteiner and Wiener4. In the typical
case (approximately 90 per cent of the cases fall into this category), the mother
is Rh-negative, the father is Rh-positive, and the fétus is Rh-positive, the latter
having inherited the factor from the father. Due perhaps to some defect in the
placenta, some of the fetal blood escapes into the maternai circulation, and in
sensitive mothers this stimulâtes the production of anti-Rh iso-antibodies.
Since the normal placenta is perméable to antibodies, the anti-Rh iso-antibodies
then filter back through the placenta into the fetal circulation and give rise to
the disease.
It might be expected on this basis that there should be a corrélation between
the titer of anti-Rh isoagglutinins in the mother's sérum and the severity of the
disease in the baby. This is not the case, however, because in some of the most
•severe instances the iso-antibodies in the mother's sérum are hardly demonstrable. The probable explanation is that the process of immunization of the mother
and the passage of the anti-Rh iso-antibodies back into the fetal circulation is
•continuous during pregnancy. One may postulate that as quickly as the isoantibodies filter through the placenta they are taken up and stored by the fetal
tissue cells. In that way their noxious action on the fetal erythrocytes is prevented at first. Only when the amount of iso-antibodies is so excessive that
saturation of the tissues occurs do the antibodies combine with and destroy the
fetal red cells. This may resuit in intra-uterine death. When the amount of
antibodies is not excessive, the baby is born alive and the hemoglobin and red
blood cell count may even be entirely normal at birth. After birth, for some
reason that is not clear, the tissue cells release the Rh antibodies which hemolyze
the infant's erythrocytes. Accordingly, the severity of the disease in such cases
dépends upon the quantity of iso-antibodies stored in the tissues and upon the
speed with which they are released.
In the past, infants with acute hemolytic anémia were treated by repeated
transfusions with varying results, though there was a definite réduction in mor"tality. The theory of Levine et al., makes possible a more rational transfusion
* Read before the twenty-second annual meeting of the American Society of Clinical
Pathologists, Chicago, Illinois, June 4 to 6, 1943.
393
394
A. S. WIENER AND I. B. WEXLER
therapy for the disease. Firstly, whole maternai blood should not be used
because in this way additional iso-antibodies may be transferred to the infant
and thus prolong the disease. For the same reason the baby should not be
permitted to nurse, as antibodies may be transferred through the colostrum and
milk. Also, the father or any Mi-positive donor should not be used since the
erythrocytes of such donors are susceptible to the action of the anti-Rh antibodies. Apparently, the tissues are capable of storing enough antibodies to
destroy not only the fetal erythrocytes but also additional Rh positive blood
introduced by transfusion. The most suitable donor is a normal Rh-negative
individual, because his cells are not sensitive to the action of the antibodies and
his sérum contains no anti-Rh iso-antibodies.
In emergencies our practice is to use group 0 Rh négative donors (with weak
anti-A and anti-B isoagglutinins in the sérum), and in this way time is saved
because grouping and matching tests may be omitted. We transfuse at once
10 ce. per pound of body weight, usually about 75 ce, and as a rule repeat this
on the following day. In the average case, this is ail that is required, since, even
if ail of the infant's own blood cells are subsequently hemolyzed, as often occurs,
the 150 ce. of donor's blood remaining contains enough erythrocytes to give the
infant a hemoglobin of about 60 per cent (assuming the infant's blood volume
to be 250 c e ) . This is sufficient to tide the infant over during the period when
the Rh iso-antibodies are gradually being eliminated from its body. During
this interval, which may last as long as a month, the infant lives entirely on the
donor's blood, and, in fact, blood grouping tests carried out at this time will
give the type of the donor and will show few or none of the baby's own cells.
Then gradually the donor's blood is eliminated and replaced by the baby's own
cells and the baby's actual type will again become apparent.
To illustrate the various points mentioned a number of cases of acute hemolytic
anémia of the newborn recently treated by us will be presented.
Case 1. The first child of the patient's mother was normal at birth, but died following a
tonsillectomy. The patient was the second child and was delivered by Caesarian section
on March 1,1943 at the Jewish Hospital of Brooklyn. At birth he was apparently normal
and weighed 6| pounds. For the first three days of life nothing unusual was noticed but
then progressive pallor was observed. The infant took his feedings well. On the fifth day
the hemoglobin was only 50 per cent. The spleen was moderately enlarged. No erythroblasts were seen in the smear. A diagnosis of acute hemolytic anémia of the newborn was
made and the child was given a total of 150 ce. of citrated blood from a group O Rh-negative
donor in two doses, on successive days. Recovery was complète and uneventful. Tests
carried out subsequently on the blood of the mother and samples of the infant's blood taken
before transfusion showed the mother to be group AB Rh-negative with anti-Rh agglutinins
in her sérum, and the baby to be group A and Rh-positive. Tests on the infant's blood
several days after the second transfusion showed it to be group O and Rh-negative, so that
the only blood in his circulation at that time was that derived from the donor. Incidentally, had the tests been made by one not familiar with the history, he might hâve concluded
that there had been a mix-up in babies since a group AB mother cannot hâve a group O baby.
This case demonstrates how in the average patient two moderate-sized transfusions of Rh-negative blood are sufficient to control the hemolytic anémia.
ACTJTE HEMOLYTIC ANEMIA OF THE NEWBORN
395
I t is also évident that had the infant not been transfused he would hâve died,
since ail his own blood was completely hemolyzed so that he survived only by
virtue of the blood he had received. An important point is that the présence of
erythroblasts in the blood smear is not essential for the diagnosis,5 The fact that
the mother is Rh-negative appears to be more important in the diagnosis.
The senior author has seen a number of other patients with erythroblastosis
who responded in a manner similar to the patient in case 1. Two of thèse, in
which the life-saving effect of the transfusions was particularly obvious and
dramatic are described below:
Case 2. The patient was a maie infant born on February 1, 1942, at the Williamsburgh
Maternity Hospital. He was the second child and had a sister two years of âge, who was a
mongolian idiot. The patient's delivery was spontaneous, his birth weight was 6 pounds
10 ounces, and nothing unusual was noted at the time of birth except for hydramnios. How«ver, he did not nurse well and was observed to beeome progressively paler, and a blood
sample examined when he was three days old showed his hemoglobin to be only 47 per cent.
Grouping tests on the blood of the infant and his parents showed the following :
BLOOD or
GROUP
SUBGKOUP
MN TYPE
Rh REACTION
Father
Mother
A
AB
A,
A2B
MN
MN
Patient
A
A2
MN
Positive
Négative, with weak anti-Rh agglutinins in the sérum
Positive
Accordingly, this was a case of erythroblastosis.
200 ce. of blood were drawn from a group O, type N, Rh-negative donor and mixed with
5 ce. of the Witebsky group substances. (This was the only case in which the group substances were used to neutralize isoagglutinins in the donor's sérum since it was subsequently
found that this procédure was not essential.) 75 ce. of blood were transfused at once into
a scalp vein, and an additional 75 ce. were given the f ollowing day. The hemoglobin rose
to 90 per cent and then dropped back to 65 per cent where it remained until the patient
was discharged, one week later. Tests on the infant's blood at this time showed it to be
group O, type N, Rh-negative so that the only blood remaining in his circulation was the
blood it had received from the donor. When the child was seen one month later and again
a year later, he was perfectly well in every way, having developed normally in eontrast to
his older sister.
Case 8. This patient was a maie infant born at the Williamsburgh Maternity Hospital
on May 3,1943. It was the first child, was delivered spontaneously, and had a birth weight
of 6 pounds 8 ounces. The infant was noticeably jaundiced at birth, the head and extremities were edematous, and there was a large hematoma on the right side of the scalp. The
edema was particularly pronounced on the eyelids, where it was so marked that it was impossible to open the infant's eyes. The infant was noticed to beeome progressively paler
and when he was two days old the blood count was only 890,000 red cells with 35 per cent
hemoglobin. By the time arrangements were completed for a blood transfusion, the condition of the infant was indeed desperate. 90 ce. of group O, Rh-negative blood were transfused at once, and 75 ce. of this blood were given the next day. Following this the hemoglobin rose to 90 per cent, and the patient showed marked clinical improvement. The
edema gradually disappeared and when the patient left the hospital two weeks later, the
hemoglobin was still 80 per cent. He was seen again at one month of âge, at which time he
appeared perfectly normal except for slight edema of one thigh. The infant appeared to be
396
A. S. WIENER AND I. B. WEXLER
developing normally, the weight now being almost 8 pounds. Incidentally, grouping tests
on the blood of the parents showed the following:
BLOOD OF
Pather
Mother
Patient
GEOOT
SUBGEOUP
Rh REACTION
AB
AB
AB
AaB
A2B
AjB
Positive
Négative
Positive
Addendum: The patient was seen again recently at the âge of 2i months, and he appeared normal except that his hemoglobin was only 55 per cent. Differential agglutination
tests demonstrated the survival of a substantial number of the donor's erythrocytes, even
at this late date. In this connection, Mollison12 has shown by this technic that in erythroblastosis transfused Rh-negative blood cells almost invariably survive for periods up to
three months and longer, while Rh-positive blood is often eliminated completely within a
few days.
The spectacular effect of transfusions of group O, Rh négative blood in cases
2 and 3 contrasts sharply with the results formerly reported when the donors
were not selected for the Rh factor. With the older treatment, the lives of fewer
patients were saved and those who did recover required more transfusions before
they did. Thèse cases also demonstrate that one should not give up hope until
the infant is actually dead, because while the infant still breathes and his circulation continues, there is still a possibility of reviving him by transfusion. Of
course, there are cases when the transfusionist is called too late. Thus, recently,
the senior author was called to transfuse an infant with hemolytic anémia and
arrived in time to see the infant take its last few breaths and die with pulmonary
edema. Blood taken from the heart of this patient immediately post mortem
showed that the hemoglobin before death must hâve been less than 10 per cent.
A case will now be described in which the disease was so mild that recovery
occurred without treatment.
Case 4- The patient was a female child. Delivery was spontaneous and the birth weight
was 8| pounds. On the day following birth, the patient was found to be extremely jaundiced. There were numerous erythroblasts in the smear. Therefore, the diagnosis of erythroblastosis was considered even though the hemoglobin was 110 per cent.
Tests for Rh gave the following results :
Father—group A, Rh-positive
Mother—group O, Rh-negative
Baby—group A, Rh-positive
Thèsefindingssupport the diagnosis, though no anti-Rh iso-agglutinins could be demonstrated in the mother's sérum. The infant was kept under observation but was not
transfused because the hemoglobin remained at a high level. The erythroblasts soon disappeared from the blood stream and the jaundice faded. When the infant was seen at the
âge of one month in the clinic she appeared to be perfectly well and had a hemoglobin of
67 per cent. At two months the hemoglobin was 70 per cent and the child was well, having
recently recovered from an attack of exanthem subitum.
This case demonstrates that mild or abortive instances of erythroblastosis
occur requiring no or only a single blood transfusion.* Probably the amount
* The authors are now in favor of transfusing even mild cases of acute hemolytic anémia
with a small amount of blood (e.g., 50 ce.) in order to forestall the possible occurrence of
hemorrhagic symptoms.
ACTJTE HEMOLYTIC ANEMIA OF THE NEWBORN
397
•of antibody stored in the tissue cells of such patients is very small. Had we not
been alert for instances of erythroblastosis this case might hâve been dismissed
as one of "physiologie icterus." It is of interest that the patient has a brother
10 years of âge who was perfectly normal at birth, and that tests on his blood
showed him to be Rh-negative.
Case 5. The patient, a female infant, 25 days old, was admitted to the Jewish Hospital
on March 15,1943 with a hemoglobin of 35 per cent and a diagnosis of acute hemolytio anémia of the newborn.
She had been delivered at another hospital where, it is stated, she was observed to hâve
become extremely pale shortly after birth. When she was seven days old the hemoglobin
was found to be 27 per cent and she was transfused with blood from an apparently compatible donor, without taking the Rh factor into account. Following the transfusion the hemoglobin rose to 36 per cent, and at 11 and 14 days, after additional transfusions, the hemoglobin was 45 per cent and 52 per cent, respectively. The exact amount of transfused
blood is not known. On account of the poor response to treatment, further studies were
carried out and the mother's blood found to be Rh-negative. This, then, was evidently
a case of erythroblastosis.
At our hospital the patient was given transfusions of Rh-negative blood totalling 160 ce.
and the hemoglobin rose from 35 per cent on admission (âge 25 days) to 80 per cent on discharge, 8 days later.
The infant was readmitted at 7 weeks of âge with a hemoglobin of 53 per cent, a red count
of 2.9 million and 1.5 per cent reticulocytes. She was given 100 ce. of Rh-negative blood
following which the hemoglobin rose to 80 per cent, and as far as has been ascertained there
has been no récurrence of the anémia.
This case differs from the first three in the large amount of blood which had to
be transfused bef ore clinical recovery resulted. This bears out the remarks made
concerning the undesirability of using random donors (who are apt to be Rhpositive) instead of selected Rh-negative donors. Where an excess of Rh
antibodies is stored in the tissue cells of the infant, thèse may destroy not only
the infant's blood but additional Rh-positive blood introduced by transfusion.
Every effort should be made to avoid this because the more blood hemolyzed
the more likely are there to be sequelae, e.g., kernicterus.
The following case is described because it is the only patient in our admittedly limited séries who died after receiving apparently adéquate transfusion
therapy.
Case 6. Patient was a female infant delivered spontaneously at term. At the time of
delivery it was noted that the amniotic fluid and vernix were yellow in color. The mother
had had nausea and vertigo during pregnancy. A deliveryfiveyears previously resulted in
the birth of a normal infant who is well at the présent time.
Shortly after birth the patient was observed to be jaundiced and pale, the liver and
spleen were enlarged, and the blood count showed a hemoglobin of 45 per cent with a red
blood count of 1.3 million. There were numerous erythroblasts in the smear. This was
evidently a case of acute hemolytic anémia of the newborn, and indeed subséquent studies
carried out showed the mother to be Rh-negative and the baby Rh-positive.
80 ce. of citrated blood from an Rh-negative donor were transfused at once into the infant's scalp veins, and the following day 50 ce. were given. On the third day the infant
appeared to be much improved though still jaundiced. The hemoglobin had risen to 85
per cent with a red count of 3,050,000. However, that evening the baby suddenly stopped
breathing and could not be revived.
398
A. S. WIENER AND I. B. WEXLER
The cause of death in this case is not clear, especially since permission for
autopsy could not be obtained. Of course, it is possible that death was due to
some condition entirely unrelated to the primary disease. One must also bear
in mind that in untreated cases death may resuit from complications of the disease such as hemorrhage, cérébral edema, etc., as well as from the acute extrême
anémia. In fact, the anémia may be mild while the hemorrhagic tendency is so
pronounced that fatal cérébral or pulmonary hemorrhage results. Merely
maintaining the hemoglobin by transfusion may not suffice to prevent thèse
serious complications and this aspect of the problem merits further investigation.
The occasional instance where the mother is Rh-positive offers a spécial
problem. If thèse cases hâve a sérologie explanation at ail, apparently some
pfoperty other than Rh could be involved.* Hère the problem of selecting
suitable donors cannot be solved as readily because there is no method available
for testing for thèse hypothetical factors. A simple solution to the problem
would be the use of the mother's blood because hère cells would be insensitive
to the action of the antibodies; however, the plasma would presumably contain
the harmful iso-antibodies. This difficulty can be circumvented by using
mother's erythrocytes, washed free of plasma with saline solution, as was done
in the following case.
Case 7. The patient was one of a pair of twins, and was born three weeks before term
with a birth weight of 4£ pounds. At the âge of one week the hemoglobin was 103 per cent
and the white count 28,600. No erythroblasts were seen in the smear. Pour days later
the hemoglobin dropped to 74 per cent, and the child was seen to be moderately jaundiced.
Rh tests were carried out and both mother and baby were found to be Rh-positive. Accordingly 100 ce. of blood were taken from the mother and the cells washed by centrifuging
the citrated blood, removing the plasma, resuspending the cells in two changes of normal
saline and finally diluting the washed cells to the original volume with normal saline solution. 45 ce. of this suspension were used to transfuse the child and the hemoglobin rose
promptly to 86 per cent. Over the next 6 days the hemoglobin fell to 77 per cent but no
further transfusions were considered necessary. At the présent writing the child is home
and well.
When mother's blood is used for transfusing newborn infants, the routine
grouping and cross-matching tests can be omitted and in this way time may be
saved. This statement holds even when the mother's group is incompatible
with that of the infant, e.g., mother A, infant O, because the normal infant
never possesses agglutinins capable of acting on the mother's blood cells.f
In apparently typical cases of acute hemolytic anémia where the mother is
Rh-negative and has demonstrable Rh antibodies in the sérum, treatment by
transfusions of Rh-negative blood sometimes does not measure up to expectations. Hère it may be that one is dealing with instances of multiple sensitization
involving some unknown factor in addition to Rh. In such cases the donor
* The rôle of subtypes of the Rh factor in such cases has been studied by Wiener (unpublished observations).
t It is important to bear in mind that after an infant of group O has been transfused
with blood from a group O donor, blood from its group A mother would no longer be compatible because of the agglutinins it has received from the donor (cf.6).
ACXJTE HEMOLYTIC ANEMIA OE THE NEWBORN
39&
should not only be Rh-négative but should also lack this hypothetical additional
factor. Hère again the use of the mother's washed cells would offer a ready
solution to the problem. It may be that the case now described was an instance
of multiple sensitization although absolute évidence for this could not be adduced.
Case 8. This white maie infant was born at terni, with a birth weight of 7 pounds 11
ounces. On the second day of life jaundice was noted and this increased progressively.
Nonetheless, the patient did well until the seventh day when he refused his feedings. Repeated blood smears during this period showed no erythroblasts. However, on the eighth
day the hemoglobin dropped to below 50 per cent and the patient's condition was found to
be poor. The liver was enlarged two fingerbreadths downward. The icterus index was
114.2.
The patient was transfused twice with 75 ce. portions of blood from an Rh-negative donor
and the hemoglobin rose to 70 per cent. Tests carried out after transfusion showed the
mother to be Rh-negative, and the baby Rh-negative. Evidently ail of the baby's own
erythrocytes had been hemolyzed and he was living on the transfused red cells alone.
Over a period of 5 days, hemoglobin fell to 65 per cent and it was deemed advisable to
give one more transfusion before discharging the infant. Inasmuch as the original donor
was no longer available, a différent Rh-negative donor was used. 75 ce. of blood were
given, but the hemoglobin instead of showing the expected rise fell to 60 per cent. We then
felt that we might be dealing with an instance of multiple sensitivity and accordingly the
baby was given the mother's washed red cells from 100 ce. of blood, diluted to the original
volume in saline, in two doses of 50 ce. each. Hemoglobin promptly rose to 80 per cent,
then dropped to 70 per cent in two days and has remained at the latter level for one month
without further therapy. The jaundice has subsided completely.
DISCUSSION
In the usual case of erythroblastosis, the appearance of the disease dépends
on the simultaneous existence of two major conditions, namely, (1) an Rh-negative mother with an Rh-positive fétus and (2) a defect in the placenta and/or a
mother capable of being sensitized. With regard to the second condition, there
is reason to believe, considering the structure of the placenta, that it is not
unusual for some fetal blood to enter the maternai circulation during the course
of a normal pregnancy. The most important factor would therefore appear to
be a mother who is readily sensitized, and this is in line with the observations on
isoimmunization following blood transfusions [cf. Wiener and Peters 7 ]. The
infrequency with which such isoimmunization occurs both during pregnancy and
following blood transfusion can be explained by postulating that only about
from 2 to 5 per cent of ail individuals respond readily to the introduction of Rh
and other foreign isoantigens by the production of spécifie isoantibodies. Further évidence supporting this view is the relatively high incidence among the
sensitive individuals of instances of multiple sensitization 8 ' 9 . Hère, moreover,
as in the case of allergie diseases or immunity in gênerai, the distinction between
sensitive and nonsensitive individuals is not an absolute one. For example, Dr.
M. G. Bohrod has recently informed us of a case in which an Rh-negative woman
had 12 Rh-positive children, ail perfectly normal except the fourth who died of
congénital heart disease; yet the 13th, 14th and 15th children ail had erythroblastosis, the former two dying as a resuit of the disease.
400
A. S. WIENER AND I. B. WEXLER
Acute hemolytic anémia of the newborn is a treacherous disease in that the
baby may appear normal at birth and yet develop an abrupt hemolytic crisis
which may cause death from anoxemia in a very short time. As soon as the
diagnosis is made or even suspected, therefore, arrangments should be made
for immédiate transfusion therapy with Rh-negative blood, since the condition
constitutes a médical emergency. No time should be lost waiting for the laboratory fmdings such as the Rh test, firstly, because there are atypical cases in which
subtypes of the Rh factor are involved11, and secondly, because of the possibility
of technical errors in determining the Rh type particularly in an emergency test.
That such errors can occur should not be surprising considering the frequency
with which mistakes are still made in the far simpler common blood-grouping
tests.
The blood is of but little use if given by the intramuscular route and only
intravenous transfusions are effective. Though transfusions in infants are
technically difficult because of the size of the veins, in trained hands the procédure
is carried out with ease and dispatch with the aid of a small, short-beveled 22
gauge needle, using a scalp vein as the avenue. In infants whose scalp veins are
poorly developed or concealed by edema, a suitable vein can as a rule be found
by making an incision anterior and superior to the medial malleolus or by incising
the antecubital fossa. In cases where the mother has given a history of previous
stillbirths or infants with erythroblastosis, the appearance of the disease can be
anticipated even before the infant is born. Hère it has been suggested that a
prophylactic transfusion be given into the umbilical vein before it is tied and eut.
An important question which has already been discussed is the type of blood
to be given. In the typical
already mentioned, Rh-negative blood is the
most suitable. Theoretically, the donor should belong to the same group as
the infant, but in practice group 0 blood serves just as well because of the relative
insensitivity of the infant's red cells to the alpha and beta agglutinins. In the
writers' opinion, the best procédure is to use an Rh négative donor of the mother's
blood group. The reason for this is that should it develop that the infant's
symptoms are due to a factor other than the Rh or to the combined effect of
anti-Rh iso-antibodies and some other iso-antibody, it would still be possible
to use the washed red cells of the mother in subséquent transfusions without
danger.
There is a marked similarity between the symptoms of acute hemolytic anémia
of the newborn and that of acute hemolytic transfusion reactions. In fact, the
hemorrhagic type of erythroblastosis is probably due to the same phenomenon
which occasionally causes hemorrhagic symptoms in acute hemolytic transfusion
reactions and in peptone and anaphylactic shock. According to Quick10, in
peptone and anaphylactic shock, as seen in expérimental animais, the incoagulability of the blood can be traced primarily to the libération of heparin and
probably, also, agglutination of platelets may be a contributing factor. With
regard to the latter possibility, it is significant that, as Diamond, Blackfan and
Baty 1 hâve pointed out, a marked réduction in the platelet count occurs in infants
with erythroblastosis. Probably, therefore, the hemorrhagic symptoms in thèse
ACUTE HEMOLYTIC ANEMIA OF THE NEWBOBN
401
infants are not due, as a rule, to the simultaneous présence of hemorrhagic disease
of the newborn, but are the resuit rather of the hemolytic process itself, and
vitamin K therapy would probably hâve little or no bénéficiai effect. To control
the hemorrhagic symptoms, transfusions of fresh whole blood or plasma (containing platelets and fibrinogen) might be effective while washed erythrocytes^
or stored blood and plasma would not be. Some infants might receive maximum
benefit from the use of mother's washed red cells suspended in the plasma of a
donor of a compatible group.
Because of the analogy between acute hemolytic anémia of the newborn and
hemolytic transfusion reactions it would be worth while to investigate cases of
erythroblastosis for the occurrence of hemoglobinuria, anuria, oliguria, and rénal
damage with uremia.
SUMMAEY
The treatment of acute hemolytic anémia of the newborn by transfusions of
Rh-negative blood was outlined and eight illustrative cases were presented. Th&
problems presejited by atypical cases due to sensitization to factors other than
Rh or due to multiple sensitization were mentioned, and transfusion with
washed mother's erythrocytes suspended in compatible plasma was suggested.
REFERENCES
(1) DIAMOND, L. K., BLACKFAN, K. D.,
AND BATY, J. M.: Erythroblastosis
fetalis and its association with universai edema of the fétus, icterus
gravis neonatorum, and anémia of
the newborn. J. Pediat., 1: 269,
1932.
(2) LEVINE, P., KATZIN, E. M., AND
BURNHAM, L.: Isoimmunization in
pregnancy and its possible bearing
on the etiology of erythroblastosis
fetalis. J. A. M. A., 116: 825, 1941.
(3) LEVINE, P., BURNHAM, L., KATZIN, E.,
AND VOGEL, P.: The rôle of isoim-
munization in the pathogenesis of
erythroblastosis fetalis. Am. J.
Obst. & Gynec, 42: 925, 1941.
(4) LANDSTEINER, K., AND WIENER, A. S.:
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Erythroblastosis fetalis and the
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C. C. Thomas, 1943, p. 70.
(7) WEINER, A. S., AND PETERS, H. R.:
Hemolytic reactions following transfusions of blood of the homologous
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Ann. Int. Med., 13: 2306, 1940.
(8) WIENER, A. S., AND FORER, S.: A
human sérum containing four distinct isoagglutinins. Proc. Soc.
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(9) WIENER, A. S., SILVERMAN, I. J., AND
ARONSON,W.: Hemolytic transfusion
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}° QUICK> A ; : Personal communication,
* S O S N P L T h I T e t i l g v of
<12> ^ 1 ^ 1 ^ ^
Z ^ î n t c ^ j l
haemolytic transfusion
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