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 rabbi ts in each arm were divided into three equal groups and treated with e ither saline (control) or 1 mg/kg body weight (bw) of a new recombinan t hirudin HBW 023 given as a single dose or standard heparin 1 mg/kg b w followed by quarter doses of heparin every half hour, Both arms incl uded a control group given equal volumes of saline, The study continue d for 2 hours. The following parameters were evaluated: bleeding times from arteriotomy/venotomy, patency rates, and the weights of thrombot ic materials. Plasma samples were taken for evaluation of anti-factor IIa (anti-FII a), anti-factor Xa (anti-Fxa), and activated partial thr omboplastin time (APTT). The bleeding times were significantly prolong ed but were still within clinically acceptable levels, following both HBW 023 and heparin treatment, Patency rates were significantly improv ed in both the arterial and venous arms following HBW 023 and heparin treatment, A corresponding reduction in thrombotic materials was simul taneously registered in the arterial and venous arms following HBW 023 and heparin treatment, Hirudin (HBW 023) significantly improved the r eduction 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, ch anged the pre-treatment levels only slightly. Anti-FIIa levels were im mediately increased by both heparin and hirudin (the highest levels) b ut 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 simultan eously prolonged significantly (still within acceptable limits) follow ing both heparin and HBW 023 treatment in the arterial arm but were on ly prolonged following heparin treatment in the venous arm. The advant age of r-hirudin HBW 023 was furthermore the single dose administratio n.