Effect of recombinant human FVIIA on warfarin-induced bleeding in rats

Recombinant human factor VIIa (rFVIIa) was given to warfarin-treated rats. One and two warfarin treatments reduced endogenous factor X levels to about 10% and less than 5%, respectively. The reduction of plasma levels of vitamin K-dependent coagulation factors was accompanied by a treatment-dependent prolongation of activated partial thromboplastin time (APTT) and prothrombin time (PT) as well as by increased bleeding time and blood loss in the rat tail bleeding test. rFVIIa 50 micrograms/kg and 250 micrograms/kg normalized PT and shortened APTT in rats given warfarin once. Bleeding was completely normalized by rFVIIa 250 micrograms/kg. In rats given warfarin twice rFVIIa 250 micrograms/kg shortened PT but had no effect on APTT, whereas the effect on bleeding was variable. The elimination half life of rFVIIa in rats was found to be 30-40 minutes. The study indicates that rFVIIa may be useful in patients with bleeding due to decreased levels of vitamin K-dependent coagulation factors.