Comparison of the antithrombotic effect of the new recombinant hirudin HBW 023 and heparin in small arteries and veins.
The study was composed of two parts, arterial and venous; the 24 rabbits in each arm were divided into three equal groups and treated with either saline (control) or 1 mg/kg body weight (bw) of a new recombinant hirudin HBW 023 given as a single dose or standard heparin 1 mg/kg bw followed by quarter doses of heparin every half hour. Both arms included a control group given equal volumes of saline. The study continued for 2 hours. The following parameters were evaluated: bleeding times from arteriotomy/venotomy, patency rates, and the weights of thrombotic materials. Plasma samples were taken for evaluation of anti-factor lla (anti-Flla), anti-factor Xa (anti-Fxa), and activated partial thromboplastin time (APTT). The bleeding times were significantly prolonged but were still within clinically acceptable levels, following both HBW 023 and heparin treatment. Patency rates were significantly improved in both the arterial and venous arms following HBW 023 and heparin treatment. A corresponding reduction in thrombotic materials was simultaneously registered in the arterial and venous arms following HBW 023 and heparin treatment. Hirudin (HBW 023) significantly improved the reduction compared with the heparin group in the venous study. Heparin treatment caused expected high levels of anti-FXa and prolonged APTT, but hirudin, being at least as effective in antithrombotic potency, changed the pre-treatment levels only slightly. Anti-Flla levels were immediately increased by both heparin and hirudin (the highest levels) but reached low levels after 2 hours of single-dose hirudin treatment, despite a simultaneously excellent antithrombotic effect. We conclude that the new recombinant hirudin HBW 023, like standard heparin, is a highly efficient antithrombotic agent in both small arteries and veins following severe vessel wall trauma. The bleeding times were simultaneously prolonged significantly (still within acceptable limits) following both heparin and HBW 023 treatment in the arterial arm but were only prolonged following heparin treatment in the venous arm. The advantage of r-hirudin HBW 023 was furthermore the single dose administration.
Department of Experimental Research, University of Lund, Malmö University Hospital, Sweden.
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Zhang
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Wieslander
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D000991:Antithrombins / Q000008:administration & dosage / Q000627:therapeutic use*; D001158:Arteries / Q000187:drug effects / Q000293:injuries / Q000648:ultrastructure; D001780:Blood Coagulation Tests; D004334:Drug Administration Schedule; D015951:Factor Xa / Q000032:analysis; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use*; D024764:Hirudin Therapy; D006629:Hirudins / Q000008:administration & dosage; D008297:Male; D010314:Partial Thromboplastin Time; D011516:Prothrombin / Q000032:analysis; D011817:Rabbits; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D016037:Single-Blind Method; D012965:Sodium Chloride; D013927:Thrombosis / Q000517:prevention & control; D014654:Vascular Patency; D014680:Veins / Q000187:drug effects / Q000293:injuries / Q000648:ultrastructure
D000925:Anticoagulants; D000991:Antithrombins; D006629:Hirudins; D011994:Recombinant Proteins; D012965:Sodium Chloride; D011516:Prothrombin; C025337:Factor IIa; D006493:Heparin; D015951:Factor Xa; C083544:lepirudin