Effect of clopidogrel on thrombin generation in platelet-rich plasma in the rat

• Published in: Thrombosis and haemostasis Vol. 81; no. 6; p. 957
• Main Authors: Hérault, J P, Dol, F, Gaich, C, Bernat, A, Herbert, J M
• Format: Journal Article
• Language: English
• Published: Germany 01.06.1999
• Subjects: Animals; Blood Platelets - pathology; Blood Platelets - physiology; Flow Cytometry; Male; Platelet Activation - drug effects; Platelet Aggregation Inhibitors - pharmacology; Platelet Aggregation Inhibitors - therapeutic use; Rats; Rats, Sprague-Dawley; Thrombin - biosynthesis; Thrombosis - blood; Thrombosis - prevention & control; Ticlopidine - analogs & derivatives; Ticlopidine - pharmacology; Ticlopidine - therapeutic use
• ISSN: 0340-6245
• DOI: 10.1055/s-0037-1614606

Clopidogrel (25 mg/kg, p.o.), a potent and selective inhibitor of ADP-induced platelet aggregation, significantly inhibited, in the presence of platelets, 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 phase of thrombin generation. Under the same experimental conditions, heparin (100 microg/ml) inhibited thrombin generation mostly by delaying and by reducing the burst of thrombin. In a stasis-induced venous thrombosis model in rats under low thrombogenic challenge, clopidogrel inhibited thrombus formation (ED50 = 7.9+/-1.5 mg/kg, p.o. - n = 10), confirming the existence of a close relationship between platelet activation and thrombin generation leading to blood coagulation and venous thrombosis.