Role of 4 platelet membrane glycoprotein polymorphisms on experimental arterial thrombus formation in men

This study investigates whether the polymorphisms of 3 important platelet receptors affected experimental thrombus formation in men. Forty healthy male volunteers randomly recruited were genotyped for the variable number of tandem repeat (VNTR) of GPIb alpha, the -5T/C polymorphism in the Kozak sequence of GPIb alpha, the 807C/T polymorphism of GPI alpha, and the pI(A1)/pI(A2) polymorphism of GPIIb/IIIa. Platelet thrombus formation was induced ex vivo by exposing a collagen-coated coverslip in a parallel plate perfusion chamber to native blood for 4 minutes. The shear rates at the collagen surface were 650 and 2600 s(-1). At 2600 s(-1) platelet thrombus formation was significantly related only to the 807C/T polymorphism. In contrast, at 650 s(-1) thrombus formation was significantly altered only by the Kozak sequence polymorphism. The VNTR and the pI(A1)/pI(A2) poly-morphisms did not influence thrombus formation. Thus, platelet thrombus formation is significantly influenced by genetic variations of the GPIb alpha and GPI alpha receptors. The effect of these polymorphisms was dependent on the blood flow rate. (C) 2001 by The American Society of Hematology.