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.
Bernat
A
A
Sanofi Recherche, Toulouse, France.
Herbert
J M
JM
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D007958:Leukocyte Count; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010976:Platelet Count; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000494:pharmacology; D013924:Thrombophlebitis / Q000188:drug therapy* / Q000473:pathology; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology
D010972:Platelet Activating Factor; D013844:Thiazoles; D004317:Doxorubicin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin; C071317:Foropafant