Effects of different hirudins and combinations of low doses of hirudin, heparin and acetylsalicylic acid in a rat microcirculatory thrombosis model.

Two recombinant hirudins (r-hirudin), natural hirudin and hirudin in combination with heparin or acetylsalicylic acid (ASA) have been studied in a thrombosis model in which rat mesenteric venules of a diameter of 20-30 microns were injured by well-defined argon laser lesions. In the animal model all hirudins showed significant and dose-dependent antithrombotic effects in doses between 0.05 and 0.1 mg/kg after single intravenous and subcutaneous injections. The antithrombotic effect of single (0.2 mg/kg i.v. or 0.1 mg/kg s.c.) injections lasted longer than 4 h (i.v.) or 6 h (s.c.). Hirudin at a dose of 0.1 mg/kg and heparin at doses of 0.05 mg/kg showed a significant antithrombotic effect 2 h after subcutaneous injection. When heparin and hirudin were injected together at this dosage, the effect of the combination was in the same range as that of unfractionated heparin or hirudin alone. An additive antithrombotic effect was observed if a low dose of r-hirudin (0.1 mg/kg) was combined with a moderate dose of ASA (10 mg/kg).