Severe Haemolytic Disease of Foetus and Newborn due to Anti-c Alloimmunisation in a Multiparous Malay Woman: A case study

Severe haemolytic disease of foetus and newborn (HDFN) is commonly caused by anti-D, anti-c and anti-K alloimmunisation. However, anti-c associated HDFN are infrequent because the majority of infants are relatively often c-negative. This case report describes a severe HDFN due to anti-c alloimmunisation in a multiparous Rhesus D positive mother. The baby was delivered prematurely at 32 weeks of gestation and unable to survive due to hydrops foetalis. Failure to detect anti-c alloimmunisation at the early antenatal period and unknown previous RBC alloimmunisation status were the main reasons for poorly suspicion of HDFN, which lead to improper foetal management and end up with foetal loss. Thus, routine antenatal RBC antibody screening during the early antenatal period is recommended for every pregnant woman with a history of HDFN or at risk for alloimmunisation for early detection and management of HDFN to prevent severe related morbidity or mortality.

Augustine Blood Group System and Equilibrative Nucleoside Transporter 1

Augustine (AUG) is a blood group system comprising four antigens: AUG1, AUG2 (At^a), and AUG4 are of very high frequency; AUG3 is of very low frequency. These antigens are located on ENT1, an equilibrative nucleoside transporter encoded by <i>SLC19A1</i>. AUG antibodies are of clinical relevance in blood transfusion and pregnancy: anti-AUG2 have caused haemolytic transfusion reactions; the only anti-AUG3 was associated with severe haemolytic disease of the fetus and newborn. ENT1 is present in almost all human tissues. It facilitates the transfer of purine and pyrimidine nucleosides and is responsible for the majority of adenosine transport across plasma membranes. Adenosine transport appears to be an important factor in the regulation of bone metabolism. The AUG_null phenotype (AUG:–1,–2,–3,–4) has been found in three siblings, who are homozygous for an inactivating splice-site mutation in <i>SLC29A1</i>. Although ENT1 is very likely to be absent from all cells in these three individuals, they were apparently healthy with normal lifestyles. However, they suffered frequent attacks of pseudogout, a form of arthritis, in various joints with multiple calcifications around their hand joints. Ectopic calcification in the hips, pubic symphysis, and lumbar discs was present in the propositus. The three AUG_null individuals had misshapen red cells with deregulated protein phosphorylation, but no anaemia or shortening of red cell lifespan. Defective in vitro erythropoiesis in the absence of ENT1 was confirmed by shRNA-mediated knockdown of ENT1 during in vitro erythropoiesis of CD34⁺ progenitor cells from individuals with normal ENT1. Nucleoside transporters, such as ENT1, are vital in the uptake of synthetic nucleoside analogue drugs, used in cancer and viral chemotherapy. It is feasible that the efficacy of these drugs would be compromised in patients with the extremely rare AUG_null phenotype.

The changing trend of alloimmunization in antenatal females: experience from a tertiary care centre in north-western India

Background: Haemolytic disease of the foetus and new-born (HDFN) is a major concern during the antenatal period, especially in countries with low human development index (HDI). The guidelines for antenatal screening and management significantly vary from one geographical region to another. Since the introduction of RhIG immunoprophylaxis, the incidence of HDFN caused by alloimmunization to D antigen has markedly reduced, while that caused by other minor blood group antigens has not been addressed significantly and needs to be given due consideration.Methods: The study was carried out to evaluate the incidence of alloimmunization and analyse various factors associated with HDFN in north-western India. A total of 1700 antenatal cases were evaluated over a period of 20 months, antibody screening and identification was performed on their samples and results were analysed.Results: Out of the 1700 cases, 21 were detected to have the presence of an alloantibody with a prevalence of 1.24%. Out of these, 11 were Rh (D) negative while the remaining 10 were Rh (D) positive. The rate for alloimmunization was higher in females who had a history of blood transfusion (1.24%), bad obstetric history (1.24%), and multigravida status (1.24%).Conclusions: Screening all pregnant females for alloimmunization to RBC antigens, irrespective of their Rh status will help in minimizing the incidence of the HDFN. The practice of providing partial phenotype matched blood to the females of the childbearing age group should be encouraged to reduce the overall incidence of alloimmunization and HDFN.

Pregnancy‐associated haemolytic anaemia: A cause not to be forgotten

Anaemia in pregnancy is common, however, only a few cases of pregnancy-associated autoimmune haemolytic anaemia have been documented. Typically, such cases involve a positive direct antiglobulin test and have the potential to cause haemolytic disease of the fetus and newborn. Rarely, no autoantibodies are detected. We report two cases of direct antiglobulin test negative haemolytic anaemia occurring in multiparous women with no cause found. Both women had a haematological response to corticosteroid therapy and delivery.

Intravenous Immunoglobulin in the Management of Severe Early Onset Red Blood Cell Alloimmunization

OBJECTIVE: We report the outcome of pregnancies treated with intravenous immunoglobulin (IVIG) for severe red blood cell alloimmunization, evaluating whether IVIG defers the development of severe fetal anaemia and its consequences. BACKGROUND: Although fetal anemia can be treated very successfully with intrauterine transfusion (IUT), procedures before 20 weeks' gestation can be very challenging technically and may be hemodynamically stressful to an extremely premature and already compromised fetus. The procedure-related fetal loss rate is approximately 5.6% for IUTs performed &lt; 20 weeks' gestation, compared to 1.6% overall. IVIG may prevent hemolysis and could therefore be a noninvasive alternative for early transfusions. STUDY DESIGN: We included consecutive pregnancies over a nineteen year period in the Fetal Medicine Unit, Mount Sinai Hospital, University of Toronto, Canada, of alloimmunized women with a history of severe early onset haemolytic disease who received IVIG until intrauterine transfusion could safely be performed. Previous untreated pregnancies were used as controls. IVIG therapy was commenced between 11 and 14 weeks' gestation. Our usual protocol was IVIG 2 g/kg per week every 3 weeks, until the first IUT could be performed. Each 2g/kg dose was administered over 2 days, 1g/kg per day, to reduce the chance of severe headaches. In three pregnancies, IVIG 1g/kg was given weekly. We compared the clinical outcomes (gestation at first IUT, fetal Hb at first FBS, gestation at delivery, perinatal survival) between previous pregnancies without IVIG and the subsequent pregnancy treated with IVIG. In comparing fetal Hb's between two pregnancies, a linear relationship between fetal Hb and gestation was used to correct for variable gestations. The fetal Hb was converted to a standardized fetal Hb value (multiples of the standard deviation [SD]). Statistical analysis was performed on 'Statistical Package for Social Science Version 16.0' (SPSS Inc, Chicago, Illinois). RESULTS: Seventeen women referred to our unit for a previous pregnancy loss secondary to severe RBC alloimmunization received IVIG treatment in 20 subsequent pregnancies; all eventually requiring intrauterine transfusion. For previous early losses despite transfusion, immunoglobulin was associated with a relative increase in fetal hemoglobin between treated and untreated pregnancies of 32.6 g/L (95%CI 15.2-50.0, P=0.003) and improved perinatal survival (8/8 vs 0/6, P=0.001). For previous losses &lt;20 weeks, it enabled first transfusion deferral in subsequent pregnancies to at least 19.9 (mean 23.2) weeks. Of the 17 live-born babies from IVIG-treated pregnancies, three (18%) required an exchange transfusion, eight (47%) a simple "top-up" transfusion, and six (35%) phototherapy. CONCLUSION: Our results show that, among severely sensitized cases with previous early fetal loss despite IUT, use of IVIG in subsequent pregnancies is associated with a significantly higher fetal Hb before first IUT, deferral of first IUT, delivery at a later gestation and increased perinatal survival. The timing of the first FBS/IUT was delayed by 3 weeks in pregnancies treated with IVIG compared to a previous untreated pregnancy. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Sago Haemolytic Disease: A Case Due to Climate-Induced Food Insecurity in Western Province, Papua New Guinea

Sago haemolytic disease (SHD) is a rare but significant condition presenting in sago starch-eating populations in Western Province, Papua New Guinea. Although rare, case fatality rates are high, and no known antidote is available. The exact cause of the disease is unknown, but it is believed to be secondary to mycotoxins produced by fungi in old sago. In this case report, a 50-year-old female was treated in a low-resource setting in Middle Fly, with fluid resuscitation and transfusion, making a full recovery without complications. The mainstay of treatment for SHD is intravenous fluid resuscitation and strict fluid balance, which can be achieved in even the most remote Western Province aid post. Increased food insecurity, secondary to climate change, may see the incidence of this condition increase. Therefore, all health workers in Western Province should be comfortable with fluid resuscitation and fluid balance practices.

Molecular red cell genotyping of rare blood donors in South Africa to enhance rare donor-patient blood matching

Background: Molecular red cell genotyping is devoid of serology limitations such as the scarcity of rare antisera and the possibility of inconclusive results due to biological interferences. Blood incompatibility can result in immune transfusion reactions such as haemolytic transfusion reactions or haemolytic disease of the foetus and newborn.Objective: The study aimed to use molecular red cell genotyping to identify rare blood group donors among South African blood donors.Methods: Red cell genotyping data were extracted retrospectively from the BIDS XT genotyping software in the Immunohaematology Reference Laboratory from January 2015 to August 2016. The ID CORE XT genotyping assay was used to identify the single nucleotide polymorphisms of 10 blood groups system alleles in 150 donors. Associations between the resultant genotypes and predicted phenotypes, ABO group, RhD type, race group and gender were studied.Results: Significant red cell genetic variability was noted among the numerous South African donor genotypes identified in this study. Genotyping further confirmed the presence of at least one of the 16 rare genotypes in 50 donors. Group O Black donors were associated with two rare blood types, while several other rare blood types were found only in White donors, supporting an association between ABO/Rh subtype, race group and rare blood types.Conclusion: Targeted screening of donors for antigen-negative rare blood units for patients should be done to reduce the risk of haemolytic transfusion reactions and haemolytic disease of the foetus and newborn.

Unusual case of immune haemolytic disease causing severe neonatal cholestasis in a newborn

Neonatal hyperbilirubinaemia is a very common entity witnessed in most of the newborns. Rarely are there events where the bilirubin levels reach extreme values mandating invasive therapy. Unconjugated hyperbilirubinaemia when solely present is easy to manage and diagnose the common aetiological factors associated with it. The issue arises when we come across a mixed picture of conjugated with unconjugated hyperbilirubinaemia and puts us in a dilemma as to what are we treating. Our case highlights a similar picture where we witnessed the highest documented levels of total bilirubin but to our surprise the major component of which was direct bilirubin. This report takes us through the differentials which were ruled out and our management strategies for solving this rare mystery.