A RECOMBINANT HIRUDIN (IK-HIRO2) IN HEALTHY-VOLUNTEERS .2. EFFECTS ONPLATELET-ADHESION AND PLATELET-INDUCED THROMBIN GENERATION TIME

The pharmacodynamic effects of different intravenous and subcutaneous doses of a new recombinant hirudin (IK-HIR02) on platelet adhesion, pl atelet-induced thrombin formation and on platelet count have been stud ied in 18 healthy volunteers in a bicenter study, Single intravenous b olus injections of 0.1, 0.2 and 0.3 mg/kg IK-HIR02 in 6 volunteers cau sed a significant dose-dependent prolongation of platelet-induced thro mbin generation time (PITT) and a significant inhibition of platelet a dhesion to glass. Single subcutaneous doses of 0.1, 0.25 and 0.5 mg/kg IK-HIR02 slightly prolonged PITT and inhibited platelet adhesion to g lass for up to 8 h, Repeat subcutaneous injections of 0.3 mg/kg IK-HIR 02 b.i.d. in 6 healthy volunteers led to a prolongation of PITT and al so to a reduction of platelet adhesion, In platelet-rich plasma (PRP) from blood samples which had been collected using hirudin as anticoagu lant (0.7 mu g/ml), the platelet count was constantly higher than in c itrate PRP which had been sampled at the same time. The recombinant hi rudin IK-HIR02 inhibits platelet adhesion to glass and also PITT, Both effects which have not been described before are most likely due to a direct inhibition of thrombin-induced platelet activation. These effe cts may contribute to the antithrombotic action of hirudin and probabl y have to be considered when hirudin is used in higher doses as an ant ithrombotic agent together with platelet function inhibitors to avoid excessive bleeding.