Evidence that donors with variant RH genotypes are associated with unexpected Rh antibodies.

BACKGROUND: We previously reported unexpected Rh antibodies in the plasma of patients with sickle cell disease (SCD) that demonstrated common Rh specificities in the absence of transfusion of RBCs positive for that antigen. We hypothesize that these antibodies might result from transfusion of antigen-negative donor units with variant RH genotypes. METHODS: Plasma testing by tube and IgG gel, extended RBC phenotyping, and HEA and RH genotyping were by standard methods. CASE: A 6-year-old female with SCD, phenotype D + C-c + E-e + K- undergoing exchange transfusion with CEK- and Fy(a-) units, presented with anti-C in the plasma, a + DAT and warm autoantibody (WAA) in the eluate. Her RH genotype was unremarkable: RHD*D/DAU0 and RHCE*ce/ce(48C). Units (n = 10) transfused over the prior 6 months were confirmed CEK- by serology and DNA testing. Most (n = 7) were Rh-negative. A unit with variant RH, RHD*DIIIa/weak partial 4.0, RHCE*ceVS.03/ceVS.02, was transfused 5 weeks prior. Anti-C and + DAT continued to demonstrate for 25 weeks. Total hemoglobin and % Hgb S did not deviate from her established baseline. CONCLUSION: We show direct association of plasma anti-C with transfusion of a C-negative unit with variant RH encoding partial D and uncommon V/VS+ hrB - phenotype. The antibody was transient, without evidence of compromised survival of transfused RBCs. The +DAT and WAA complicated workups and selection of units, and it is uncertain whether donors of the same genotype should be avoided. Minority donors are important for CEK-matching to avoid depleting Rh-negative supplies. Consideration of patient and donor RH genotypes may avoid unexpected antibodies and improve allocation of rare donations.

Clinical and molecular characterization of novel deletions causing epsilon gamma delta beta thalassemia: Report of two cases.

Epsilon gamma delta beta (εγδß)0 - thalassemia is a very rare disorder that results from large deletions in the ß-globin gene cluster which abolish all regional globin chain gene expression from that allele. Since it is an exceedingly rare cause of neonatal anemia and is not detected by routine newborn screening, it is usually not suspected clinically and commonly undiagnosed or misdiagnosed. In this study, we describe two patients diagnosed in our hospital with (εγδß)0-thalassemia based on the results obtained from DNA microarray analysis of their peripheral blood. The first patient of mixed European descent presented as a neonate with microcytic hemolytic anemia, hyperbilirubinemia, hypoglycemia and hypothermia, and was found to have a 2.2 Mb loss that included the entire ß-globin gene cluster and the locus control region (LCR). The second patient, also of mixed European descent, presented in the neonatal period with anemia, thrombocytopenia and cutaneous extramedullary hematopoiesis, and was found to have a 59 kb loss that included the ß-globin LCR, HBE1, HBG1, and HBG2 genes. Both cases highlight the importance of recognizing the clinical features of (εγδß)0-thalassemia and implementing appropriate testing to clarify the diagnosis and manage the condition.