Integrin beta-3 subunit (platelet glycoprotein IIIa, β3 integrin), specifically the human platelet antigen 1a (HPA-1a) variant. (ITGB3 (for the gene encoding the protein); GPIIIa (for the protein), HPA-1a (for the specific antigenic variant).)

Human platelet antigen 1a (HPA-1a) is a single amino acid polymorphism (Leu33) on the β3 integrin subunit (platelet glycoprotein IIIa, ITGB3) expressed on the surface of platelets as part of the αIIbβ3 integrin receptor (also known as GPIIb/IIIa), which mediates platelet aggregation and adhesion. HPA-1a represents the most clinically significant platelet alloantigen in Caucasian populations, particularly as the major cause (∼80%) of severe fetal and neonatal alloimmune thrombocytopenia (FNAIT) and post-transfusion purpura (PTP). Alloantibodies to HPA-1a develop when individuals lacking the antigen (typically HPA-1b homozygotes) are exposed to HPA-1a–positive platelets, often through pregnancy or transfusion, resulting in immune destruction of platelets. The antigen is fully exposed on the flexible loop of the PSI domain of β3 integrin, distant from the ligand binding site, and plays no known direct physiological role in platelet function. However, its polymorphism is highly immunogenic and underpins several important transfusion-related disorders.

Other names

HPA-1aPl A1 (previous nomenclature)Zw aHuman platelet alloantigen 1aAntigenic variant of integrin beta-3 subunit (ITGB3 gene product)Platelet glycoprotein IIIa, β3 integrin (Leu33 variant)

Inhibition of platelet aggregation by blocking ligand binding to αIIbβ3 integrin (GPIIb/IIIa) (For immune-mediated disorders): Alloantibody formation against HPA-1a leads to platelet destruction