Maternal alloimmunization against the rare platelet‐specific antigen HPA‐9b (Maxa) is an important cause of neonatal alloimmune thrombocytopenia

Abstract

Neonatal alloimmune thrombocytopenia (NATP) is an important cause of morbidity and mortality in the newborn. Optimal management of subsequent pregnancies requires knowledge of the alloantigen that caused maternal immunization, but this is possible only in a minority of cases. This study investigated whether this can be explained in part by maternal immunization against the "rare" alloantigen HPA-9b (Max(a)), implicated previously only in a single NATP case. Archived paternal DNA from unresolved cases of NATP and normal individuals was typed for platelet (PLT)-specific antigens with real-time polymerase chain reaction and direct sequencing. PLT-specific alloantibodies were characterized by flow cytometry and solid-phase enzyme-linked immunosorbent assay. Recombinant GPIIb/IIIa was expressed in stably transfected Chinese hamster ovary cells. Clinical information was obtained directly from attending physicians. Six of 217 fathers were positive for the presence of HPA-9b (Max(a)), an incidence about seven times that in the general population. In each of five cases studied, maternal serum samples reacted with intact paternal PLTs and paternal GPIIb/IIIa. Only one of three serum samples tested recognized recombinant GPIIb/IIIa carrying the HPA-9b (Max(a)) mutation. These seemingly discrepant reactions may reflect different requirements for oligosaccharides linked to residues close to the mutation in GPIIb that determines HPA-9b (Max(a)). NATP in the affected children was severe and was associated with intracranial hemorrhage in three of six infants on whom information was obtained. Maternal immunization against HPA-9b (Max(a)) is an important cause of NATP and should be considered in cases of apparent NATP not resolved on the basis of maternal-fetal incompatibility for "common" PLT antigens.