Cases Of Erythroblastosis Fetalis Research Articles

Biological significance of the York, Cost, McCoy and Knops alloantibodies

The biological significance of alloantibodies directed against the red blood cell antigens York, Cost, McCoy, and Knops has been investigated by means of a literature search and an analysis of 304 patient referrals received since 1965. Neither method detected documented cases of erythroblastosis fetalis due to these antibodies. The analysis of the patient referrals identified 11 women immunized by pregnancy. The literature search provided one documented case of hemolytic transfusion reaction and one probable case of successful transfusion of incompatible blood. The analysis of the patient referrals revealed two cases of probable successful transfusions of incompatible blood, nine patients with documented evidences of extravascular hemolytic transfusion reactions, and one patient with documented evidence of intravascular hemolytic transfusion reaction. The conclusion reached is that alloantibodies directed against the York, Cost, McCoy, and Knops antigens are biologically significant with respect to red blood cell transfusions in some patients. Transfusion practices show that most patients have received compatible transfusions, an indication that the physicians in the hospitals adhere to the philosophy of compatible transfusions, whenever possible.

ERYTHROBLASTOSIS DUE TO ANTI-RH6.

A case of erythroblastosis fetalis is described in which the sole demonstrable antibody was anti‐Rh6. The mother is the third reported example of the phenotype Rh:1,2,3,4,5,‐6 who has produced anti‐Rh6.

Anti-Jkb in erythroblastosis fetalis

Cases of erythroblastosis fetalis caused by anti-Jkb are reported.

Erythroblastosis fetalis caused by sensitization tofactor rh w(C w)

<h2>Summary</h2> A case of erythroblastosis fetalis caused by sensitization to the rare factor rh^w(C^w) in a seventh child is presented. This factor was present in the blood of the father and the third, fifth, and sixth child born to the mother, and to the seventh child discussed in this report. The significance of a positive direct antiglobulin test on cord blood and the value of routinely performing this test on blood of all newborn infants is emphasized.

Localization of homologous plasma proteins in the human placenta by fluorescent antibody

Normal and abnormal human placentas, as well as specimens of hydatidiform mole and choriocarcinoma, have been surveyed for homologous plasma albumin and globulin by the fluorescent antibody technique. Protein has been found broadly dispersed throughout the stromal ground substance of the villi, decidua, and cord, as well as in the intervillous spaces. Slight specific localization has been noted in the trophoblastic cytoplasm, but not within nuclei. Syncytial knots have shown somewhat higher levels of cytoplasmic protein accumulation. Albumin and gamma globulin exhibited similar distribution, and all placental material, including that from a case of erythroblastosis fetalis, presented similar topography. Syncytial masses in the choriocarcinoma revealed intracytoplasmic localization, while the mole showed a general diffusion through the vesicular stroma. The findings do not indicate synthesis of blood protein by the human placenta, but rather point to a transfer of maternal albumin and globulin across the syncytium, perhaps by pinocytosis and subsequent discharge into the villous stroma.

Treatment of erythroblastosis fetalis, with special reference to sensitization to Rh-Hr factors other than Rh 0

<h2>Summary</h2> To date, 166 babies with erythroblastosis fetalis caused by <b>Rh₀</b> sensitization have been treated by our latest modification of exchange transfusion by the radial artery-saphenous vein technique. In this latest modification, partially concentrated blood (hematocrit 0.5), preferably not more than three days old, is used. This is prepared by removing part of the citrated plasma after sedimentation has occurred. Depending on the severity of the disease and the size of the baby, from 450 to 900 ml. of such concentrated blood is used for the transfusion. In severe cases the exchange transfusion is repeated. In no instance are more than two exchange transfusions deemed necessary. Among the 166 babies treated this way, only five babies died or had neurological sequelae, a crude mortality rate of only 3.0±0.9 per cent. On the other hand, among babies treated by our earlier modifications, or by only simple transfusion, or receiving no treatment at all, the mortality rate ranged from 17 to 21 per cent. The difference in results is even more striking when the severity of the disease is taken into account. Thus, among severely affected babies who received no treatment the mortality rate was 65.5±10.6 per cent; among those receiving simple transfusion therapy the mortality rate was 42.1±7.8 per cent; among those treated by our previous methods of exchange transfusion the mortality rate was 19.8±2.6; while among those treated by our latest modification of exchange transfusion, the mortality rate was only 3.8±1.0 per cent. The cases of erythroblastosis fetalis caused by sensitization to Rh-Hr factors other than <b>Rh₀</b> pose an important problem, since the routine antenatal screening test for <b>Rh₀</b> sensitization does not take them into account. Such cases are rare, but when they occur they are just as serious as instances of <b>Rh₀</b> sensitization. Thus, among nine cases of erythroblastosis fetalis caused by <b>hr′</b> sensitization, one baby died before treatment could be instituted. Of the remainder, four were treated by exchange transfusion and recovered uneventfully, while among the four treated by simple transfusion one died and one of the three who survived had severe neurological sequelae. A simple screening test for <b>Rh₀</b> antibodies consists in testing the serum of the patient against ficin-treated cells of types Rh₁Rh₁, Rh₂, and rh, respectively. This test should be carried out on all patients in labor admitted to the obstetrical service, and on patients admitted to the surgical or other services, who might require blood transfusion therapy. Case histories are presented, which illustrate the value of this screening test. It is pointed out that in cases of <b>hr′</b> sensitization the antibodies, even when present in high titer, may react only in tests against enzyme-treated cells and may fail to react in the conglutination and antiglobulin tests. This accounts for puzzling, severe cases of erythroblastosis fetalis in which the direct antiglobulin test for coating of the baby's red cells by Rh-Hr antibodies is negative. It is emphasized that certain antibodies, such as anti-<b>F</b> and anti-<b>J</b> are not detected by the enzyme test, so that the screening test against ficin-treated cells should supplement and not replace the other tests for isosensitization.

Erythroblastosis fetalis due to factor c(hr'); a practical method for investigating sensitization to Rh subgroup factors.

Erythroblastosis fetalis (hemolytic disease of the newborn) is a disease wherein the clinical laboratory attains special achievement, inasmuch as the diagnosis, prognosis, and prescription for therapy may be provided by means of laboratory procedures. As a matter of fact, a great deal may be accomplished prior to the birth of the patient. Thus, it seems worthwhile to re-emphasize 2 points that are pertinent to this problem in the average clinical laboratory: 1. The staff of the laboratory should be prepared for a practical solution to the problem when the disease is the result of factors other than D(Rh0). Allen 1 estimated that AB, K, c, E, and C factors account for approximately 20 per cent of all instances of erythroblastosis fetalis. Recent papers u indicate that ABOincompatibility may be the cause of erythroblastosis fetalis more frequently than previously recognized, but most of these patients have only a slight degree of disease that might be overlooked. Even the obvious clinical cases pose a vexing diagnostic problem that will not be discussed in this paper. 2. The cross-matching procedure should include technics that enable detection of incompatibilities of minor groups. This is highly important, owing to the fact that the routine procedures for typing usually include the identification of only 3 of at least 16 blood factors that are clinically significant, and cross-matching is relied upon for the detection of incompatibility from the other factors. This paper deals with a case of erythroblastosis fetalis that resulted from sensitization to c(hr') factor; a delay in accurate diagnosis and adequate therapy was attributable to the use of an unreliable cross-matching technic that is used rather commonly. Further studies with methods that may be used in the average clinical laboratory revealed that sensitization to c(hr') factor was the underlying cause of the erythroblastosis.

The treatment of erythroblastosis fetaliswith replacement transfusion

One hundred six cases of erythroblastosisfetalis have been treated with exchange transfusion. There were seven deaths, giving an over-all mortality of 6.6 per cent. The indications for early exchange transfusion are enumerated. The practical and theoretical advantages of exchange transfusion are discussed. One hundred six cases of erythroblastosisfetalis have been treated with exchange transfusion. There were seven deaths, giving an over-all mortality of 6.6 per cent. The indications for early exchange transfusion are enumerated. The practical and theoretical advantages of exchange transfusion are discussed.

Exchange transfusion in hemolytic disease of the newborn.

To the Editor:— Any case of erythroblastosis fetalis should be taken under care prenatally. Every pregnant woman should have her Rh blood type ascertained. If she is Rh negative and her husband is Rh positive, blood should be drawn in the third month of pregnancy to test for the presence or absence of antibodies to the Rh factor and to be used as a basis for comparison with subsequent samples. This should be done even in primiparas, because of the possibility of previous transfusion with Rh-positive blood, of its intramuscular injection, or of a previous undiagnosed incomplete pregnancy. Other titers may be obtained according to individual discretion, but at least one titer should be obtained in the seventh month of pregnancy for comparison. If there is a rise in titer, hemolytic disease should be anticipated. Generally speaking, those women with the highest rise in titer will deliver the most severely

Erythroblastosis fetalis in the Negro infant: Report of five cases, including four cases due to A-B-O incompatibilities

Summary Five cases of erythroblastosis fetalis have been presented in Negro infants. Four cases had clinical and serologic findings consistent with the type described by Halbrecht as icterus precox. Only one case exhibited typical Rh sensitization. That A-B-O sensitization can occasionally cause severe damage is reflected in one case which developed kernicterus but survived. Polayes 10 similarly reported kernicterus in an infant who died on the fifth day of life with hemolytic disease produced by anti-A agglutinins. The pertinent clinical features of our cases are summarized in Table I. It is noted that all patients recovered. Only one infant exhibited a complication (kernicterus). The infant with Rh sensitization presented characteristic symptoms at birth; however, the cases due to A-B-O sensitization did not develop significant findings until three to five days following delivery. On the basis of our experience with erythroblastosis in Negro infants, we are inclined to concur with the observation of Wiener and Zuelzer that most cases of erythroblastosis in Negro infants are due to A-B-O incompatibilities (icterus precox) and not to Rh sensitization which is rare in this race.

STUDY OF CARDIAC ENLARGEMENT IN INFANCY WITH CASE REPORTS OF REVERSIBLE ENLARGEMENT

The heart was considerably enlarged in 16 of 1,000 infants subjected to roentgenographic examination in the neonatal period. Seven of this group died shortly. Seven of the surviving cases continued under observation for several years: five had some congenital malformation of the heart, but in the remaining two cases the cardiac enlargement receded and no sign of any organic defect remained. Etiology of Cardiac Enlargement in Neonates Coming to Autopsy It was considered that autopsy examination would provide the most accurate information concerning the etiology of all types of cardiac enlargement, including reversible forms. Accordingly, records and pathologic material were examined from 200 consecutive autopsies on infants born alive at the Boston Lying-in Hospital but dying in the neonatal period. Criteria based on weight are more reliable than those based on size, even though cases with pure dilatation may be excluded. Cases were selected from this series in which the heart weighed more than 25 gm. This figure of 25 gm. was selected to avoid inclusion of borderline cases, due to variations in technic and slight differences in age. A considerable number of cases with enlargement of lesser degree were thereby excluded. In 29 of the 200 cases reviewed, the heart weighed more than 25 gm. The causes of death are listed in Table II. It would be anticipated that intrauterine aspiration or atelectasis might be complicated by supervening infection, and in most cases a combination of more than one of the conditions enumerated occurred. Separation into individual types was therefore impracticable. In the tissue sections from this group, the cardiac muscle fibers were not hypertrophied, but in every case changes due to congestion and edema were apparent. These changes did not necessarily correspond in intensity to the degree of cardiac enlargement; thus, in the largest heart of the series (weight, 54 gm.), from a case of intrauterine aspiration with minimal pneumonic changes, cardiac congestion and edema were only slight. [See Table II in source PDF] Group 2 calls for no further description. Cardiac enlargement in fatal cases of erythroblastosis (Group 3) has long been recognized, but it is interesting to speculate whether it occurs to any significant degree in cases which survive. Among the miscellaneous cases (Group 4), one had previously been labelled "idiopathic cardiac hypertrophy"; microscopic changes associated with aspiration were, however, present in the lungs, though to a slight extent, and this case should more correctly be included in Group 1. Three cases are described in which cardiac enlargement in infants receded over a considerable period. In two of these cases, cardiac hypertrophy appeared to originate in association with pulmonary infection. Some other possible causes of reversible cardiac enlargement are discussed. To determine the incidence of all forms of cardiac enlargement, including reversible enlargement, 1,000 infants were examined roentgenologically in the neonatal period. In 16 patients, considerable cardiac enlargement was present. Of these, seven died shortly. Among the nine survivors, two were lost sight of, five had a congenital malformation of the heart and two recovered with an apparently normal heart. To investigate the etiology of neonatal cardiac enlargement, the material from 200 consecutive autopsies was reviewed. In 29 cases considerable hypertrophy of the heart was found: in eight of these a congenital malformation of the heart was present, six were cases of erythroblastosis fetalis and in five some miscellaneous cause produced the cardiac enlargement: In the remaining 10 cases some pathologic condition of the lungs was present. It is suggested that some cases of cardiac hypertrophy are associated with pathologic lung conditions occurring before, during or after birth. The association is not necessarily fatal and the cardiac enlargement may prove reversible.

Erythroblastosis fetalis associated with Rh-positive mothers

F OLLOWING close upon Landsteiner and Wiener ' s I discovery of the Rh factor, Levine and his associates 2 developed the idea of maternal isoimmunization i n the pathogenesis of erythrob]astosis fetalis, demonstrating the relationship between Rh incompatibili ty and erythroblastosis fetalis. In over 90 per cent of the cases the fa ther and child were Rh positive and the mother, Rh negative. Clinically, erythroblastosis fetalis is considered as a single disease with three chief recognized forms, called fetal hydrops, icterus gravis, and congenital anemia. Erythroblastosis fetalis is generally considered as being synonymous with Rh incompatibili ty and associated with Rh-negative mothers in over 90 per cent of the eases. However, not ~11 cases of erythroblastosis fetalis are caused by the Rh antigen-antibody reaction. On a theoretical basis, incompatibilities can occur f rom any blood antigen which is present in the father, t ransmit ted to the offspring, and absent in the mother. The Rh subgroups, the H r factor, and ABO group incompatibilities are possible etiological agents. The M, N, and P factors are apparent ly not antigenic. Tovey a gives four reasons why the fetus enjoys protection from the mother 's agglutinins in heterospeeific pregnancies :

Erythroblastosis fetalis in a premature infant from a mother with sickle cell anemia: A report of a patient successfully treated by exchange transfusion

Summary<ul><li>1.A case of erythroblastosis fetalis in a premature infant from a motherwith sickle cell anemia is reported.</li><li>2.Treatment was by exchange transfusion with a successful end result.</li><li>3.The transfusion technique is described.</li><li>4.The rationale for the treatment of icterus gravis by exchange transfusion is briefly discussed.</li></ul>

SOME OBSERVATIONS UPON THE RH FACTOR IN PREGNANCY

Summary No final conclusions are presented. We have listed some impressions formed as as result of treating six cases of erythroblastosis fetalis with the hope that, when combined with the experience of others, they may serve as a basis for the future management of Rh-negative mothers and their babies.

THE INFLUENCE OF HUMAN SERUM ALBUMIN ON EDEMA IN ERYTHROBLASTOSIS FETALIS

Summary Two cases of erythroblastosis fetalis complicated by severe generalizededema successfully treated with concentrated human serum albumin are reported. The first was one of twins, in which the untreated sibling died. In the second case, blood studies were done and it was found that the use of the serum albumin corrected an early fall in the blood protein level with subsequent elimination of the severe generalized edema. It is postulated that liver damage, frequently a feature in severe erythroblastosisfetalis, with a disturbed blood protein level was the causative mechanism of the edema, and that the serum albumin restored the level. Studies are now in progress further to elucidate these factors.

A case of erythroblastosis fetalis caused by isoimmunization with the agglutinogen B

A case of erythroblastosis fetalis caused by isoimmunization of an Rhpositive, type O mother by a type B baby is reported with confirmatory blood serologic findings. It is suggested that when an erythroblastotic infant is seen, whose mother is type O and her Rh factor is unknown, the baby be transfused with type O, Rh-negative blood. This would obviate the possibility of giving the infant blood to which he has circulating isoagglutinins. A case of erythroblastosis fetalis caused by isoimmunization of an Rhpositive, type O mother by a type B baby is reported with confirmatory blood serologic findings. It is suggested that when an erythroblastotic infant is seen, whose mother is type O and her Rh factor is unknown, the baby be transfused with type O, Rh-negative blood. This would obviate the possibility of giving the infant blood to which he has circulating isoagglutinins.

Some Observations Upon the Rh Factor in Pregnancy

Summary No final conclusions are presented. We have listed some impressions formed as as result of treating six cases of erythroblastosis fetalis with the hope that, when combined with the experience of others, they may serve as a basis for the future management of Rh-negative mothers and their babies.

Erythroblastosis fetalis: A report of four cases

1.1. Four cases of erythroblastosis fetalis, two of congenital hydrops, one of icterus gravis neonatorum with recovery, and one in an infant who died four hours after birth are reported. Blood Kahn tests on all were negative.2.2. An interesting family history of many miscarriages, early infant deaths, and the death of three infants with severe jaundice was obtained from the mother of one of the cases of congenital hydrops. The family history in the other cases was not conclusive.3.3. Post-mortem examination of three of the cases revealed hepatomegalia, immature cells in the circulating blood, and extramedullary centers of hematopoiesis. Two of the infants had splenomegalia.4.4. Following frequent small transfusions totaling 720 c.c. of citrated blood to the patient with icterus gravis neonatorum, the liver and spleen gradually decreased in size, the jaundice diminished, the anemia improved, and the patient was apparently quite fully recovered in thirty days.5.5. Erythroblastosis fetalis may be suspected if the placenta is large, pale, and friable, and there is an increased amount of amniotic fluid which may or may not be yellow tinged.

Erythroblastosis fetalis as a cause of fetal mortality

Two and possibly three cases of erythroblastosis fetalis are described. They were the only outwardly normal full-term or near full-term infants received in the embryology laboratory, and two of the three were found to be cases of erythroblastosis fetalis when examined at autopsy, although the infants had been regarded as normal by the obstetrician. It is suggested that this condition may be a cause of many stillbirths at or near term, and of many deaths formerly attributed to prematurity and it may go unrecognized because it does not always cause external manifestations, such as hydrops or jaundice. The obstetrician may receive blame for mismanagement of the case because of the death of the infant. The lives of some of these children might be saved by induction of labor while the fetus is still viable, followed by transfusion, if the obstetrician is aware that the mother has given birth to other offspring with erythroblastosis. Such knowledge will be gained only by subjecting all stillbirths, premature infants and outwardly normal fullterm infants, dying immediately after birth, to routine pathologic inspection. Just as “senility” has given way to a more adequate classification in most cases, so “stillbirths” and “prematurity” will give way to more accurate cataloguing as the causes of death are more scientifically determined.