A new low-frequency platelet alloantigen, Vaa, on glycoprotein IIbIIIa associated with neonatal alloimmune thrombocytopenia

We describe platelet alloimmunization which caused severe thrombocytopenia in a neonate and could only be detected by testing the father's platelets. The platelet-specific antibodies were identified by a monoclonal antibody-immobilized platelet protein assay (MAIPA) using monoclonal antibodies against glycoprotein (GP) IIbIIIa complex (AP2 and 2G12). The previously described alloantigen systems on the GPIIbIIIa complex (HPA 1, HPA 3 or HPA 4) were not responsible for the reaction. In addition the newly described private platelet antigen Sra was not identical to the antigen. The antigen is therefore different from all known platelet alloantigens and was designated Vaa. The antigen was present on the platelets of the affected child. Family studies showed that the platelet antigen was transmitted as an autosomal dominant trait in three generations. No Va (a+) individuals were found in a population study of 250 blood donors, which indicates that the antigen is of low frequency in the Finnish population. The Va antigen was not detectable by immunoblot analysis, which suggests that the epitope may not be a linear peptide structure. The antigen was also destroyed by solubilization of platelets. Thrombin activation of platelets, known to increase the expression of GPIIbIIIa on platelets, did not increase the number of binding sites for anti-Vaa antibodies to the extent observed with anti-HPA 1a binding.