Comparative antithrombotic effects of heparin, recombinant hirudin and argatroban in a hamster femoral vein platelet-rich mural thrombosis model.
The antithrombotic properties of bolus i.v. injections of heparin, of recombinant hirudin (r-hirudin) or of the synthetic competitive thrombin inhibitor Argatroban were investigated in a quantitative hamster femoral vein platelet-rich mural thrombosis model. Heparin at a dose of 100 U/kg prolonged the activated partial thromboplastin time from 26 +/- 15 to 177 +/- 45 sec (P = .001), but did not significantly inhibit platelet-rich thrombus formation (7 +/- 44% inhibition, P = NS vs. placebo). However, 400 U/kg of heparin produced total inhibition of thrombus formation (101 +/- 14+, P less than .06 vs. control). R-hirudin and argatroban inhibited thrombus formation in a dose-dependent manner: 50% inhibition was obtained with 1.4 mg/kg for r-hirudin and with 2.0 mg/kg for Argatroban. A linear correlation was observed between the percentage of inhibition of thrombus formation vs. Activated partial thromboplastin time (r = 0.57, P = .003 for r-hirudin and r = 0.66, P = .002 for Argatroban). These results suggest that thrombin plays a pivotal role in platelet-rich mural thrombus formation, that this small animal model may be useful for investigation of the pharmacodynamics of synthetic thrombin inhibitors and that platelet-rich thrombus formation is inhibited effectively by heparin, r-hirudin and Argatroban. However, r-hirudin and Argatroban cause less profound changes in the coagulant function at doses that inhibit platelet-rich thrombus formation than heparin.
Imura
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Center for Thrombosis and Vascular Research, University of Leuven, Belgium.
Stassen
J M
JM
Collen
D
D
D000818:Animals; D000991:Antithrombins / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives; D006224:Cricetinae; D005268:Femoral Vein / Q000187:drug effects; D006493:Heparin / Q000627:therapeutic use*; D024764:Hirudin Therapy; D007275:Injections, Intravenous; D008297:Male; D008955:Models, Cardiovascular; D010314:Partial Thromboplastin Time; D010875:Pipecolic Acids / Q000627:therapeutic use*; D013449:Sulfonamides; D013918:Thrombin Time; D013927:Thrombosis / Q000517:prevention & control*
D000991:Antithrombins; D010875:Pipecolic Acids; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban