Effect of clopidogrel on thrombin generation in patelet-rich plasma in therat

Clopidogrel (25 mg/kg, p.o,), a potent and selective inhibitor of ADP-induc ed platelet aggregation, significantly inhibited, in the presence of platel ets, ex vivo thrombin generation triggered by low concentrations of tissue factor. Clopidogrel reduced the area under the curve (23%, p <0.05) and the thrombin peak concentration (35%, p <0.05) but did not affect the lag phas e of thrombin generation. Under the same experimental conditions, heparin ( 100 mu g/ml) inhibited thrombin generation mostly by delaying and by reduci ng the burst of thrombin. In a stasis-induced venous thrombosis model in ra ts under low thrombogenic challenge, clopidogrel inhibited thrombus formati on (ED50 = 7.9 +/- 1.5 mg/kg, p.o. - n = 10), confirming the existence of a close relationship between platelet activation and thrombin generation lea ding to blood coagulation and venous thrombosis.