Rh-positive Mothers Research Articles

Hemolytic Disease of Newborn Following Anti-C and Anti-S Alloimmunization

Background: Non-Rhesus D antigen non-ABO, minor blood group alloimmunization in pregnant women is being increasingly recognized as a significant contributor to the development of the hemolytic disease of the fetus and newborn (HDFN). We report severe HDFN in a neonate born to an Rh-positive mother with sickle cell disease, following anti-C and anti-S alloimmunization. Clinical Description: A male baby born to a repeatedly transfused mother with sickle cell disease developed severe jaundice at 22 h of life. The baby was found to have severe anemia and indirect hyperbilirubinemia, but no encephalopathy, hepatosplenomegaly, or features of sepsis. Management and Outcome: His blood group was O positive and the direct Coombs test was 4+. Minor blood group typing showed the presence of anti-C and anti-S antibodies. The baby improved after receiving a double-volume exchange transfusion with matched blood and phototherapy. Conclusion: Severe hemolytic disease of the newborn (HDN) may be caused by minor blood group alloimmunization, especially seen in mothers with a history of multiple transfusions. Antenatal screening for alloimmunization in high-risk mothers can ensure timely diagnosis and treatment of HDN and prevent the harmful effects of neonatal hyperbilirubinemia.

Non RhD isoimmunization causing severe hemolytic disease of fetus and newborn in Rh positive pregnancies: report of 2 cases with review of literature

Anti D immunoprophylaxis widespread use in antenatal patients has led to dramatic reduction in the rates of alloimmunization due to anti D, which is the most common Rh antibody causing severe Hemolytic Disease of Fetus and New born (HDFN). However, there has been increase in the rates of non Rh D antibodies causing alloimmunization in pregnant women and leading to moderate to severe HDFN. We hereby report two cases of neonates presenting with moderate to severe HDFN with strongly positive DAT due to Rh anti-c antibody in Rh-positive mothers. Thus, antenatal antibody screening should be done in all Rh-positive pregnant women to prevent the diagnostic delay of HDFN occurring due to Non anti-D isoimmunization in the fetus.

An Autopsy Case of Severe Nonimmune Hydrops Fetalis Secondary to Premature Closure of the Foramen Ovale

Abstract Hydrops fetalis is a condition in the fetus characterized by excessive fluid accumulation within the fetal extravascular compartments and body cavities occurring prenatally. Nonimmune hydrops fetalis is the predominant (>85%) cause of all affected individuals (cardiovascular is the leading etiological category). Herein we present an autopsy case of severe nonimmune hydrops fetalis. The decedent was delivered from a blood type A Rh-positive mother. The overall autopsy findings are diffuse subcutaneous edema, significant ascites, pleural effusion, and pericardial effusion. The major autopsy finding is the premature closure of the foramen ovale of the heart, in addition to enlarged heart and liver. Premature closure of the foramen ovale may occur at any stage of pregnancy and may be due to multiple causes and has been reported as a cause of hydrops fetalis. It is well known that the foramen ovale is the shortcut through which the fetal heart provides oxygenated blood to preferential organs, mainly the brain and the heart itself, and normally closes at birth. The timing of the premature closure of the foramen ovale in fetus is critical: its closure late during pregnancy has been associated with right heart failure, while its closure very early during pregnancy frequently results in a hypoplastic left heart due to decreased blood flow, with an aneurysm consistently bulging into the left atrium, which ultimately leads to right heart failure. Both, if uncorrected in time, can ultimately lead to hydrops fetalis and fetal death. Other structural abnormalities, like pulmonary vascular disease/irreversible pulmonary hypertension, and enlarged edematous placenta, may further aggravate obstruction to venous return to fetal heart, setting up a vicious cycle. In summary, the newborn baby died of complications of nonimmune hydrops fetalis due to the premature closure of the foramen ovale of the heart.

Anti-D-induced severe hemolytic disease of the newborn in an Omani newborn born a rhesus-positive mother

Abstract Hemolytic disease of the fetus and newborn (HDFN) due to anti-D antibodies is a well-known complication of rhesus (Rh) incompatibility, encountered in D-positive babies born to alloimmunized D-negative mothers who have been sensitized during previous labor or abortion. Here, we report a case of significant hemolytic disease of the newborn due to the presence of anti-D antibodies in an Rh-positive baby born to an Rh-positive mother. The boy presented at day 1 of life with neonatal jaundice and required intensive phototherapy. His hemoglobin (Hb) concentration gradually dropped from 17 g/dL to 6.6 g/dL. The blood bank workup revealed O Rh-positive blood group, with a positive direct antiglobulin test (DAT) and confirmed the presence of anti-D antibodies. His mother was typed as O Rh positive, with a negative DAT and positive anti-D. He required two blood transfusions, and his Hb stabilized at the age of 7 weeks. Anti-D HDFN is a rare complication of Rh-positive and Rh-weak positive pregnancies. The lack of awareness of this phenomenon is often a source of confusion for clinicians. A literature review of similar cases and possible explanations are discussed.

Hemolytic disease of newborn: Can think beyond Rh (D) and ABO incompatibilities

The widespread use of Rh-D immune globulin has led to a relative increase in the importance of non-Rh-D isoimmunization as a cause of hemolytic disease of the fetus and newborn (HDN). Disease spectrum for non-anti-D erythrocyte alloimmunization may range from subclinical hemolysis to active hemolysis and hyperbilirubinemia requiring exchange transfusion. We report such a case of HDN due to Rh anti-c in an infant of an Rh-positive mother, who required double volume exchange transfusion.

A Case Report of Haemolytic Disease of Foetus and Newborn due to Anti-E Antibody in a Primigravida Patient

Anti-E antibody is one of the frequently encountered alloantibody of the Rh blood group system; however, it is seldom implicated in haemolytic disease of the foetus and newborn (HDFN). This case report describes a mild HDFN due to anti-E antibody in a full term baby-girl born to a primigravida patient. The baby developed jaundice on the first day of life. Blood group of both mother and the baby was B positive and Rh phenotype was CDe/CDe (R1R1) and CDe/cDE (R1R2) respectively. Anti-E and anti-c was identified in the mother while baby’s blood showed weak positive Direct Antiglobulin Test with anti-E identified from the baby’s serum. The baby was started on phototherapy and was discharged well on day-6. Although this was a mild HDFN, we would like to highlight the importance of antenatal screening for pregnant mothers. The antibody screening for Rh-positive mothers is not a routine practice in many centers in Malaysia due to cost-benefit constraints. However, we would like to suggest to include the antenatal red cell antibody screening test for all pregnant mothers at least during the 1st antenatal booking to enable early detection of alloantibody which may cause HDFN, thus enable close monitoring of foetus and initiate early management as needed.Bangladesh Journal of Medical Science Vol.15(1) 2016 p.139-141

Changing Times for the IJHBT.

I welcome you to 2016 with the latest 120-page issue of our journal, up from the 70 pages previously. In this issue too, we maintain our focus on original articles and reviews for the printed journal, and increasingly hope to move towards special online editions for case reports and letters to the Editor. The invited reviews in his issue focus on the old and the new. On one hand, they deliberate on how the advent of genomics and personalized medicine is revolutionizing the way we diagnose and manage hematological malignancies [1, 2]. On the other, they remind us that good medicine is based on astute evaluation of all evidence, be it from fashionable new techniques or from conventional ones that have stood the test of time. In that regard, the diverse monoclonal protein electrophoretic patterns reviewed by Misra et al. [3] reveal myeloma to be as intriguingly heterogeneous a disease at the paraprotein level as it is at the genomic, morphological and clinical levels. As chemotherapeutic management and acute care of hematological malignancies improve across the country, quality-of-life issues are assuming greater importance. In this issue, Kumar et al. [4] investigate growth impairment and short stature among children treated for acute lymphoblastic leukemia, while Rohilla et al. [5] report on obstetric outcomes in women with chronic myelogeneous leukemia. Another tricky management issue is the judicious management of elderly AML or high-risk MDS, and this is addressed by a Turkey study which looks at epigenetic modifiers alone as well as in combination with low-dose cytosine arabinoside in such patients. New technologies often bring with them new and unexpected complications. Among the benign disorders, Dubey et al. [6] investigate how life-saving intra-uterine blood transfusions to Rh-negative fetuses of Rh-positive mothers may carry the risk of inducing additional maternal antibodies against fetal antigens, thereby aggravating Rhisoimmunization. Sen et al. [7] similarly caution that highpressure carbon dioxide insufflation, commonly used in laparoscopic surgeries, may depress natural anticoagulant systems as well as fibrinolysis thus contributing to surgeryassociated thrombophilia. In the midst of these rapidly changing times for hematology in general and the journal in particular, the coming of the New Year offers us an opportunity to pause, reflect and take stock. The entire Editorial Board welcomes your inputs on what you think the IJHBT’s goals for the future should be, and how best can they be realized. Comments, suggestions and letters from readers on published articles and ongoing events are, as always, welcome. Wishing everyone a very happy new year ahead.

The clinical significance of ABO blood group incompatibility

To compare incidence, severity, and treatment of jaundice in ABO-compatible and -incompatible infants. Retrospective chart review. A 340-bed acute-care public and teaching hospital. All infants with blood groups A or B delivered in 1990 by Rh-positive mothers with blood group O. On direct antiglobulin testing 65 infants had positive and 78 had negative results. The control group comprised 78 infants with blood group O born to mothers of blood group O. None. Infants who were ABO-incompatible and showed positive results to the direct antiglobulin test had the highest incidence of jaundice and underwent more tests and phototherapy. Infants who showed negative results to the direct antiglobulin test had jaundice incidence rates between those seen for control infants and infants who tested positive. Mean peak bilirubin levels did not differ significantly among the groups. Incompatibility of ABO blood group is associated with an increased incidence of jaundice and higher phototherapy rates. Clinicians should continue to be concerned about possible ABO incompatibility in infants with jaundice born to mothers with blood group O.

Segregation distortion in Rh polymorphism

Segregation distortion for the Rh system is reported. Mother-infant pairs (1018 pairs) from maternity service divisions of government hospital and 216 complete families with a total of 692 children, of Visakhapatnam (Andhra Pradesh, South India) were typed for the D-d alleles of Rh system. The segregations analysis made by means of the T matrix method of ITO matrices, assuming Hardy-Weinberg equilibrium, reveals that: Rh-positive mothers produce fewer Rh-negative children with significance and Rh-negative mothers produce more Rh-positive children with less significance than expected in both the mother-child and family studies. This results in a reduction in the d allele from mothers to their children. Known Rh antigenic specificities and reproductive compensation do not explain the observed distortion. Other selectively acting forces probably linked to Rh compatibility system seem to be operating to gain d alleles to maintain Rh polymorphism.

Screening of Rh-antibodies in Rh-negative female infants with Rh-positive mothers.

The sera of 96 consecutive Rh-negative female infants born to Rh-positive mothers were examined at birth, and sera from 88 of these infants were examined for the presence of Rh-antibodies at the ages of about three and eight months. A two-stage papain test and an AutoAnalyzer method were used for antibody screening and identification. Weak anti-D antibodies were found by the papain and AutoAnalyzer techniques in two cord sera, In neither case could the antibodies be demonstrated in samples taken on later occasions. Weak anti-D antibodies were found by the AutoAnalyzer technique but not by the manual methods in the sera of two other infants at the age of eight months. These antibodies could still be demonstrated by the same technique in samples taken about one month later. Though far from conclusively, the results support the "grandmother theory", but because of the low incidence of sensitization and uncertain nature of the anti-D antibodies demonstrable only by the AutoAnalyzer technique, anti-D prophylaxis is not recommended for newborn Rh-negative female infants with Rh-positive mothers.

Maternal-fetal hemorrhage: Its incidence and sensitizing effects

Although anti-Rh-immune globulin is highly effective in preventing hemolytic diseases of the newborn, there are some failures. The causes for these failures often are unknown and it has been postulated that some of them are caused by the transfer of maternal Rh-positive red cells into the Rh-negative infant at the time of birth. A study of 107 Rh-negative newborn infants born of Rh-positive mothers has demonstrated that maternal-fetal hemorrhage is rare (approximately 2 per cent) and that Rh antibody produced during the first six months in Rh-negative babies is similarly rare. Routine administration of anti-Rh gamma globulin to Rh-negative neonates is not indicated.

Erythroblastosis fetalis due to anti-S antibody

<h2>Summary</h2> Hemolytic disease of the newborn infantdue to isosensitization by the S blood group factor in an Rh-positive mother resulted in postnatal hyperbilirubinemia and a "late anemia" syndrome in the infant. In our case, as well as in two of the three previously reported cases, the isosensitized pregnancy followed previous blood transfusions.

Rh blood group of grandmother and incidence of erythroblastosis.

Maternal red cells may cross the placental barrier and enter the fetal circulation, and this transfer may cause primary sensitization in Rh-negative girls born to Rh-positive mothers. 60 families were studied. Each family consisted of the grandmother, her Rh-negative daughter, and the Rh-positive grandchildren. Only families with ABO compatibility in the three generations, and where the mothers had never been transfused or had never received blood intramuscularly, were selected. The families were divided into 2 groups: the group of the Rh-positive grandmothers, group (+), which consisted of 40 families, and the group of Rh-negative grandmothers, group (-), which consisted of 20 families. The 2 groups were analysed as to the presence of affected grandchildren in any pregnancy. There were 35 (87·5%) affected grandchildren in group (+), and 15 (75%) affected children in group (-). In group (+) the number of mothers with 3 or more Rh-positive pregnancies was 16, and of these, 4 (25%) had only unaffected children. In group (-) 15 mothers had 3 or more Rh-positive pregnancies, and of these, 4 (27%) had only unaffected children. There was a striking similarity in the percentage of affected children between the 1st birth in group (+), 20%, and the 2nd birth in group (-), 20%; the 2nd birth in group (+), 38%, and the 3rd birth in group (-), 30%; the 3rd birth in group (+), 28%, and the 4th birth in group (-), 25%. It was concluded that (1) an Rh-positive grandmother acts similarly to the antigenic stimulation caused by pregnancy and the birth of an Rh-positive fetus; (2) it might be advisable to inject all Rh-negative newborn females, born to Rh-positive mothers, with anti-D γ-globulin, soon after birth; (3) prediction of the risk of erythroblastosis, especially in the case of primigravidae or mothers with one non-affected Rh-positive child, requires the investigation of the blood group of the grandmother on the mother9s side.

Sensitization of Rh-negative daughters by their Rh-positive mothers.

THE prediction of immunologic tolerance by Burnett and Fenner1 suggested that tolerance to the Rh antigen might be induced in Rh-negative girls born of Rh-positive mothers.2 Immunologic tolerance was considered possible because maternal red cells cross the placenta to the fetus in at least some pregnancies.3 4 5 6 A contrary opinion held that the few authenticated cases of hemolytic disease, in first-born infants of mothers who had received no known stimulus, might be due to sensitization acquired by the mother in utero.7 , 8 This study was undertaken to determine whether Rh-positive mothers induce immunologic tolerance or primary sensitization in their Rh-negative daughters . . .

Rh Antigens and Immunological Tolerance

THE discovery of the phenomenon of immunological tolerance has raised the possibility that the nature of a mother's Rh blood-type may affect the reactivity of her children towards Rh antigens1–3. The simplest possibility is that the Rh-negative women born of Rh-positive (as opposed to Rh-negative) mothers should be relatively tolerant of Rh antigens as a result of an exposure to those antigens in fœtal life; and this tolerance might reveal itself by their being less readily immunized against the Rh antigens of an Rh-positive fœtus, or by their bearing fewer children afflicted by haemolytic disease.

EVIDENCE FOR ACTIVELY ACQUIRED TOLERANCE TO Rh ANTIGENS

Billingham et al. [1] reported that mice and chickens injected as embryos with cells from other strains acquired a persistent tolerance to later skin grafts from the donor strains. It seemed possible to us that a similar, but naturally acquired, tolerance might be in part responsible for the variation in response of Rh-negative persons exposed to the Rh antigens. [2] The hypothesis to be tested was that Rh-negative children of Rh-positive mothers might, as a result of their exposure as embryos to the maternal Rh antigen, acquire a degree of persistent tolerance toward the antigen. Rh-negative children of Rh-negative mothers, on the other hand, could have had no similar embryonic exposure and might therefore be expected to react more easily upon encountering an Rh-positive antigen in later life. We have collected data on the mothers of two groups of Rh-negative women: first, those in whom there is no evidence of Rh sensitization within three Rh-positive pregnancies and, second, those who have developed evidence of Rh sensitization during or before their third Rh-positive pregnancy. The first-group we classify as relatively tolerant and the second as relatively intolerant to Rh antigens. Table 1 lists the Rh types of the mothers of women in these two groups. A simple χ^2 test for homogeneity yields a probability of less-than 0.01 that the two samples of mothers could have been drawn by chance from the same population. In other words, these data seem to offer good reason to believe that the degree of Rh tolerance displayed by Rh-negative women is indeed related to their mothers' Rh types. A number of cases included in the study have been omitted from Table 1 because of uncertainties in their classification. For example, stillbirths or miscarriages of unknown Rh type made it impossible to classify some of them according to the criteria of tolerance we have employed. Some of the data that are included in Table 1 are open to question on other grounds. Ten of the women were given transfusions or injections of blood at some time prior to their third Rh-positive pregnancy. Some of these transfusions were with Rh-positive blood, others with blood of unknown Rh type, and others probably with Rh-negative blood. Two additional women believed that they might have received injections or transfusions of blood but were not certain that they had. It is difficult to evaluate the number of exposures of these twelve women to Rh antigens or to weigh the sensitizing significance of blood injections or transfusions relative to the importance of an Rh-positive pregnancy. Table 2 lists the data after the exclusion of all cases in which there is a record suggesting that blood may have been transfused or injected. A χ^2 test for homogeneity on the data of Table 2 yields a probability of less than 0.001. It should be noted that transfusions or injections with Rh-positive blood appear to provide a very effective stimulus to Rh sensitization and that a considerable number of the Rh-negative daughters of Rh-positive women who fall in the intolerant class have been stimulated by this route.

Hemolytic Disease of the Newborn Infant Caused by Maternal Sensitization to the Blood Factor hr' (c): Report of Two Cases with Special Reference to the Etiologic Significance of Multiple Blood Transfusions in Rh Positive Women Prior to Gestation

1. Intragroup Rh incompatibility between an Rh-positive mother and an Rh-positive infant presents an unusual pattern of maternal isosensitization.2. The antibody found in the sera of two Rh-positive mothers appeared to be of anti-hr’ (anti-c) specificity.3. Evidence of hemolytic disease in both infants was found and the findings directly correlated with this maternal antibody.4. The welfare of the infant greatly depends on prompt recognition of this unusual pattern of maternal isosensitization and proper treatment of its disease.5. An attempt has been made to evaluate the role of multiple transfusions of619Rh-negative blood which had been given to an Rh-positive mother four years prior to gestation.6. The wide spacing of several transfusions or transfusion and pregnancy respectively appears to be probably the most important factor in the development of isosensitization.7. The possible danger in using Rh-negative blood as a universal safe donor is briefly discussed.

ERYTHROBLASTOSIS FETALIS ASSOCIATED WITH RH-POSITIVE MOTHERS

ERYTHROBLASTOSIS FETALIS ASSOCIATED WITH RH-POSITIVE MOTHERS

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 :

Anti-Hr Serum of Levine

IN 1941, Levine1 in New York described a rare type of anti-Rh serum which was called anti-Hr. This antibody was found in the serum of an Rh-positive mother of an erythroblastotic infant. Unfortunately, the weakness of the antibody did not allow the genetics of its corresponding red blood cell antigen to be worked out2.