The effect of recombinant factor VIIa (NovoSeven (TM)) in healthy volunteers receiving acenocoumarol to an International Normalized Ratio above 2.0

Vitamin K antagonists are most commonly used in long-term thrombosis prophy laxis and the use in patients with cardiovascular disease seems to be incre asing. By interfering with the normal hemostatic mechanism, an increased ri sk of bleeding will arise and administration of human plasma or prothrombin complex concentrates may be necessary. It can be difficult to normalize he mostasis using plasma and prothrombin complex concentrates, because these m ay be associated with thromboembolic side-effects. The level of factor VII, one of the vitamin-K-dependent coagulation factors, decreases during oral anticoagulant therapy and the administration of recombinant factor VIIa nor malizes the prolonged prothrombin time in warfarin-treated rats. After admi nistration of acenocoumarol (International Normalized Ratio > 2), decreased levels of factor X and factor IX (19-46%), protein C (2-20%) and factor VI I (4-17%) were found in 28 healthy volunteers. After one dose of recombinan t factor Wa (5, 10, 20, 40, 80, 120, 160, 240, or 320 mu g/kg) the Internat ional Normalized Ratio and prothrombin time normalized, which may imply an effect on bleeding in individuals receiving oral anticoagulant therapy. The lowest dose (5 mu g/kg) normalized the International Normalized Ratio for 12 h and doses > 120 mu g/kg normalized it for 24 h. Fragment 1+2 stayed wi thin its normal range in all dose groups, indicating that no systemic coagu lation occurred. (C) 1998 Lippincott Williams & Wilkins.