Both blood platelets and genetics contribute to the development of acute ischemic arterial diseases. A careful analysis of the various clinical association studies supports a modest increased risk for coronary artery disease events in carriers of the PIA2 polymorphism of GPIIIa. Investigations with both platelets and stable cells lines have shown the pI(A2) polymorphism is prothrombotic. Only a handful of studies have been performed for platelet GPIa (integrin (alpha (2)) and GPIb-IX-V, but there is support for the 807 T/C polymorphism of GPIa and the met145 and VNTR B/C genotype of GPIb(alpha) as risk factors in younger age groups. And isolated reports suggest other platelet polymorphisms (GPIIb, Fc gamma RIIa, P-selectin, alpha2 adrenergic receptor, transforming growth factor [TGF]beta) are risk factors for arterial disease or produce a prothrombotic phenotype. Platelet glycoprotein polymorphisms should be added to the list of genetic risk factors for arterial thrombosis, particularly in younger patients and women. (C) 2000 Lippincott Williams & Wilkins, Inc.