The effect of platelet PIA polymorphism on experimental thrombus formationin man depends on blood flow and thrombogenic substrate

A number of studies have reported conflicting data on the association of th e PIA1/PIA2 polymorphism of the GPIIIa gene and coronary syndromes. We have investigated the effect of this polymorphism on experimental platelet thro mbus formation in man. Forty healthy male volunteers were genotyped for the PIA1/PIA2 polymorphism. Thrombus formation was induced ex vivo by exposing a tissue factor (TF) or a collagen-coated coverslip in a parallel plate pe rfusion chamber to native blood for 2 and 4 min. The shear rates at these s urfaces were 650 and 2.600 s(-1). Platelet and fibrin deposition was quanti fied by immunoenzymatic methods. The frequencies of PIA1/PIA1 and PIA1/PIA2 genotypes were 52.5% and 47.5%, respectively. Ex vivo deposition of fibrin on TF was not affected by the PIA1/PIA2? polymorphism. However. the ex viv o platelet deposition at 650 s(-1) was higher in blood from PIA1/PIA2 indiv iduals than in PIA1/PIA2 individuals (P = 0.008 at 4 min). On collagen, nei ther fibrin nor platelet deposition was significantly affected by the PIA1/ PIA2 polymorphism. Platelet thrombus formation is significantly influenced by genetic variations in the GPIIIa platelet receptor. This effect depends on the blood flow properties and the nature of the thrombogenic stimulus.