Ethical Issues and Management of Fetal Hemolytic Anemia Caused by Anti-Rh17 in a Multipara with Rare –D– Phenotype

Abstract

<b><i>Background:</i></b> The development of allo-anti-Rh17 (anti-Hr0) in a –D– phenotype whose red blood cells (RBCs) lack CcEe antigens is most likely triggered by transfusion, transplantation, or pregnancy. Gene conversion is the predominating factor in generating RHD-CE-D and RHCE-D-CE hybrids like –D–. <b><i>Methods:</i></b> We report here immunohematological and obstetrical data from 2 of the 5 pregnancies of a 24-year-old woman presenting with the –D– phenotype with anti-Rh17. Blood group typing, antibody screening, antibody differentiation, direct antiglobulin test (DAT), and antibody titers were performed by routine gel technology and tube testing. Additionally, molecular genetic analysis was performed. Fetal surveillance was done by sonographic evaluation of the fetal middle cerebral artery peak systolic velocity (MCA-PSV). <b><i>Results:</i></b> Blood group typing showed O, C-c-D+E-e- and the DAT was negative. DNA sequencing revealed homozygosity for an <i>RHCE-D(3–9)-CE</i> null allele. Anti-Rh17 titers in the fourth pregnancy remained between 1:8 and 1:128, and no signs for a fetal anemia were observed. However, in the fifth pregnancy, the antibody titers increased up to 1:4,096. Signs of moderate fetal anemia were detected and cesarean section was performed at 34 + 6 weeks of gestation. The newborn presented with hemolytic anemia (cord blood hemoglobin [Hb] = 8.5 mg/dL). She received 2 compatible (small) packed RBC concentrates, phototherapy, and intravenous immunoglobulins. <b><i>Conclusion:</i></b> Our case shows that the risk for hemolytic complications increases with the number of pregnancies of sensitized women. Only people who also lack CcEe antigens are compatible as donors. The role of such rare donors as lifesavers, their freedom, and voluntariness conflict with the urgent need for compatible blood.

Integrated analyses reveal unexpected complex inversion and recombination in RH genes

“…Rh17(Hr 0 )-negative individuals can become immunized through transfusion or pregnancy, and alloimmunization caused by anti-Rh17 is known as a critical factor for HDFN. 17 , 27 Finding a suitable donor for an individual with a rare Rh deficiency is difficult owing to the scarcity of the D-- phenotype. Once identified, D-- individuals should be enrolled in a rare blood library available for donation for individuals with the same phenotype.…”

Characterization of Novel RHD Allele Variants and Their Implications for Routine Blood Group Diagnostics

“…The weak D phenotypes are usually caused by missense mutations in the transmembraneous or cytosolic parts of the encoded RhD polypetide, whereas most partial D variants are based on missense mutations in extracellular protein segments at the surface of erythrocytes [7,15]. As RhD and RhC proteins are determined by two homologous genes closely linked and present in chromosome 1, additionally, gene hybridization between the RHD and RHCE genes can cause partial D or rare null alleles [16]. Adding to the complexity, the presence of a C encoding allele in trans position to the RHD carrying allele in a heterozygous D positive genotype can weaken the expression of D, known as the "Cepellini effect".…”