BACKGROUND: We report an obstetric case involving an RhD-positive woman who had developed a red blood cell (RBC) antibody that was not detected until after delivery of a newborn, who presented with a positive direct antiglobulin test result. Immunohematology studies suggested that the maternal antibody was directed against a low-prevalence antigen on the paternal and newborn RBCs.
RESULTS: Comprehensive blood group profiling by targeted exome sequencing revealed a novel nonsynonymous single nucleotide variant (SNV) RHCE c.486C>G (GenBank MZ326705) on the RHCE*Ce allele, for both the father and newborn. A subsequent genomic-based study to profile blood groups in an Indigenous Australian population revealed the same SNV in 2 of 247 individuals. Serology testing showed that the maternal antibody reacted specifically with RBCs from these two individuals.
CONCLUSIONS: The maternal antibody was directed against a novel antigen in the Rh blood group system arising from an RHCE c.486C>G variant on the RHCE*Ce allele linked to RHD*01. The variant predicts a p.Asn162Lys change on the RhCE protein and has been registered as the 56th antigen in the Rh system, ISBT RH 004063.
CONCLUSIONS: This antibody was of clinical significance, resulting in a mild to moderate hemolytic disease of the fetus and newborn (HDFN). In the past, the cause of such HDFN cases may have remained unresolved. Genomic sequencing combined with population studies now assists in resolving such cases. Further population studies have potential to inform the need to design population-specific red cell antibody typing panels for antibody screening in the Australian population.

Hemolytic disease of the fetus and newborn (HDFN) may cause severe cholestasis with direct bilirubin concentrations reaching up to 50 times the upper limit of normal. This case report describes twins whose highest direct bilirubin concentrations were 32.2 mg/dL and 50.2 mg/dL, with no significant signs of hepatic impairment. The index pregnancy was complicated by Rhesus factor immunization with anti-D antibodies present in maternal serum, which caused fetal anemia requiring intrauterine blood transfusions. Complementary tests demonstrated Rhesus D alloimmunization as the sole cause of cholestasis. To the best of our knowledge, this is the first study to describe such elevated direct bilirubin concentrations caused by HDFN.

Hemolytic disease of the fetus and newborn (HDFN) is a challenging condition that may necessitate the need for intrauterine or neonatal transfusion. The ability to provide compatible blood depends on antibody identification and antigen prevalence. We describe the case of a newborn that was affected by HDFN secondary to a high-prevalence antigen of unknown specificity.
A 29-year-old mother underwent emergency cesarean section for fetal distress. The newborn had severe anemia and hyperbilirubinemia. Antibody screening and identification on maternal plasma revealed pan reactivity with negative autocontrol. The cord sample had the same pattern with positive Direct Antiglobulin Test. Incompatible group O red blood cells were transfused to the newborn with no complications.
Testing the maternal sample at a reference laboratory revealed the presence of anti-U at a high titer.
In life-threatening conditions, it may be necessary to transfuse incompatible units. In patients who require transfusion in the presence of an identified antibody against a high-prevalence antigen, sources for rare blood should be explored. These include autologous donations for adults, collecting blood from relatives (including mothers), and fresh or frozen units from rare donors through rare donor registries.

The widespread use of anti-D immunoglobulin has resulted in a relative increase in the importance of non-D alloimmunization as a cause of hemolytic disease of the fetus and newborn (HDFN). Non-D alloantibodies that are capable of causing severe HDFN include anti-K, anti-E, and anti-c. Anti-c is clinically the most important Rh system antibody after anti-D. Here, we report three cases of neonates presenting with anemia and hyperbilirubinemia with strongly positive direct antiglobulin test who required phototherapy and neonatal exchange transfusion due to non-D antibody in RhD positive antenatal women. Anti-c was common in all the three cases while two cases have one additional non-D antibody. Due to faulty practices, antenatal antibody screening was not done for any case considering the mother\'s RhD positive status. Hence, antenatal antibody screening should be performed routinely, in all RhD positive pregnant women to reduce the delay in diagnosis and the management of HDFN occurring due to non-D antibodies.

OBJECTIVE: Hemolytic disease of the fetus and newborn (HDFN) caused by irregular antibodies is a rare, but possibly life-threatening condition. We report a case of severe intrauterine hemolysis caused by anti-E alloimmunization, and review 16 cases in the past 15 years of our hospital.
METHODS: A woman with gestational age 28 weeks and 5 days, received emergent Cesarean section because of fetal distress. The baby was expired at the next day after delivery and the comprehensive study showed severe anemia and alloimmunization related hemolysis caused by anti-E due to high antibody titer (1: 4096).
CONCLUSIONS: Anti-E antibody is one of the most common non-Rhesus D antibodies in the pathogenesis of HDFN, but rarely leads to severe hemolysis. However, our case has the highest reported anti-E titer in HDFN and is the first case of mortality during the past 15 years in NCKUH.

BACKGROUND: Bombay phenotype (Oh ) is a rare blood group and poses unique challenges during pregnancy, including an adequate supply of blood products in case of postpartum hemorrhage (PPH) and the risk of hemolytic disease of the fetus and newborn (HDFN). Case reports of antenatal care in this cohort are scarce. Herein, we present a case of twin pregnancy in an Oh woman and outline her multidisciplinary management. We summarize the literature to better inform decision-making and patient blood management in the antenatal care of Oh women.
METHODS: A 22-year-old G1P0 presented at 15 weeks gestation with dichorionic diamniotic twins and known Oh phenotype. Hematinics were optimized to minimize anemia. Anti-H titers were tracked and were 1:256 at both 28 and 36 weeks gestation. Regular middle cerebral artery dopplers were performed to assess for fetal anemia. There was constant communication with obstetrics and anesthetics teams. Both autologous frozen and directly donated fresh red cells were available as part of a clear, detailed transfusion plan. Transfusion was not required and neither child was affected by HDFN. The neonates were group O, DAT negative, and group A, DAT positive. Maternal anti-A was detected in the neonatal eluate.
CONCLUSIONS: To our knowledge, this is only the second report of twin pregnancy in an Oh female and the first time a detailed transfusion plan has been published. Through employing patient blood management strategies, engaging a collaborative multidisciplinary approach, and establishing a clear delivery plan, the antenatal challenges of Bombay phenotype are surmountable.

BACKGROUND: Early intrauterine transfusion (IUT) is associated with a higher risk of fetal loss. Our objective was to evaluate the efficiciency of intravenous immunoglobulins (IVIG) to postpone the gestational age at first IUT beyond 20 weeks of gestation (WG) compared to the previous pregnancy in case of very severe red blood cell (RBC) alloimmunization.
METHODS: Very severe RBC alloimmunization was defined by a high titer of antibodies and a previous pregnancy complicated by a first IUT before 24 WG and/or perinatal death directly related to alloimmunization. We performed a single-center case-control study. Cases and controls were patients respectively treated with weekly IVIG infusions started before 13 WG, and without.
RESULTS: Twenty cases and 21 controls were included. Gestational age (GA) at first IUT was postponed after 20 WG in 18/20 (90 %) of patients treated with IVIG and in 15/21 (71 %) in the control group (p = 0.24). Compared to the previous pregnancy, the GA at first IUT was postponed by a median of 22 [+11; +49] days in the IVIG group and occurred in average 2 days earlier [-17 ; +12] in the non-treated group (p = 0.02). There was no difference between number of IUT and need for exchange-transfusion. IVIG treatment was associated with a significant decrease of antibodies\' quantitation.
CONCLUSIONS: In our series, IVIG tends to differ first IUT beyond 20 WG and have a significant effect in postponing the gestational age of the first IUT in patients with very severe RBC alloimmunization.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

The Jra antigen of the JR blood group system is a highly prevalent red blood cell antigen. Although anti-Jra-associated hemolytic disease of the fetus and newborn (HDFN) is generally considered mild-to-moderate, a rare fatal case was recently reported. We report the third example of HDFN-related anti-Jra with fatal outcomes. The clinical significance of anti-Jra antibody as a cause of HDFN should be reassessed.

The severity of the hemolytic disease of the fetus and newborn (HDFN) due to Jra mismatch ranges from no symptoms to severe anemia that requires intrauterine and exchange transfusions. We encountered a newborn, born to a healthy mother having anti-Jra at 38 weeks of pregnancy, who had moderate anemia, a positive direct antiglobulin test (DAT) result, no increased erythropoiesis, and no jaundice at birth. Flow cytometry revealed that the Jra antigen of red cells in the infant was nearly negative at birth, biphasic at 5 weeks, and lowly expressed at 7 months of life. We searched online for previous case reports on HDFN due to Jra incompatibility. Among 63 reported cases, excluding 25 cases, 38 were included with the present case for analysis. Of 39 newborns, 10 developed clear anemia (hemoglobin <10.0 g/dL), and 1 died, 5 developed hydrops fetalis, 4 needed intrauterine transfusion and/or exchange transfusion, and 3 received red cell transfusion after birth; overlaps were included. Among 29 neonates with no anemia, 8 needed interventions including phototherapy and γ-globulin infusion, and the remaining 21 received conservative supports only. The maternal anti-Jra titer, ranging between 4 and 2048, did not correlate with the severity of anemia, levels of bilirubin, or any interventions required. The DAT of red cells was positive in 29 of 36 fetuses/newborns tested, whereas it was often negative among anemic neonates (4 of 9) (P < .05). Hematopoiesis did not increase effectively, as indicated by reticulocyte ratios between 1.7% and 22.3%, even with the increase in reticulocytes in anemic neonates compared with nonanemic neonates (P < .05). Total bilirubin levels ranged broadly between 0.2 and 14.3 mg/dL but were generally low. The maternal anti-Jra titer and IgG3 subclass did not correlate with the morbidity of the newborns. Being identical/compatible between mothers and their infants may possibly enhance infants\' morbidity, as a weak tendency was observed (P = .053). Maternal anti-Jra may suppress erythropoiesis in fetuses via a mechanism different from the established HDFN, such as anti-D, as evidenced by the lower reticulocyte count and small increase in bilirubin in neonates. As the anti-Jra titer, IgG subclass, and DAT were not correlated with the severity, the mechanism of anti-Jra-induced HDFN remains to be elucidated.