EFFECT OF VARIOUS DRUGS ON ADRIAMYCIN-ENHANCED VENOUS THROMBOSIS IN THE RAT - IMPORTANCE OF PAF

In the rat, adriamycin increased stasis-induced thrombosis in a dose- and time-dependent manner. Two potent antiplatelet agents, clopidogrel (20 mg/kg, po) and aspirin (200 mg/kg, po) showed a strong antithrombotic efficacy (92 and 77% inhibition of thrombus formation respectively) therefore suggesting that platelets play a major role in the prothrombotic effect of adriamycin. Standard heparin, administered as a single bolus injection (3 mg/kg, iv), 5 min prior to stasis did not affect adriamycin-induced thrombosis whereas hirudin (1 mg/kg, iv) suppressed thrombus formation (98% inhibition). SR 27417, a potent PAF receptor antagonist injected iv, reduced venous thrombosis in a dose-dependent manner (14, 29 and 63% inhibition after 1, 3 and 6 mg/kg respectively). These results therefore demonstrate that adriamycin-induced venous thrombosis is highly dependent upon platelet activation.