The Effect of Platelet Pl^A Polymorphism on Experimental Thrombus Formation in Man Depends on Blood Flow and Thrombogenic Substrate

Summary

A number of studies have reported conflicting data on the association of the Pl^A1/Pl^A2 polymorphism of the GPIIIa gene and coronary syndromes. We have investigated the effect of this polymorphism on experimental platelet thrombus formation in man. Forty healthy male volunteers were genotyped for the Pl^A1/Pl^A2 polymorphism. Thrombus formation was induced ex vivo by exposing a tissue factor (TF) or a collagencoated coverslip in a parallel plate perfusion chamber to native blood for 2 and 4 min. The shear rates at these surfaces were 650 and 2,600 s^–1. Platelet and fibrin deposition was quantified by immunoenzymatic methods. The frequencies of Pl^A1/Pl^A1 and Pl^A1/Pl^A2 genotypes were 52.5% and 47.5%, respectively. Ex vivo deposition of fibrin on TF was not affected by the Pl^A1/Pl^A2 polymorphism. However, the ex vivo platelet deposition at 650 s^–1 was higher in blood from Pl^A1/Pl^A1 individuals than in Pl^A1/Pl^A2 individuals (P = 0.008 at 4 min). On collagen, neither fibrin nor platelet deposition was significantly affected by the Pl^A1/Pl^A2 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.

Key words

Blood flow - genes - platelets - risk factors - thrombosis

• References

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