Dosing with recombinant factor viia based on current evidence

Recombinant factor VIIa (rFVIIa; NovoSeven(R), Novo Nordisk, Bagsvaerd, Denmark) induces hemostasis in patients with severe hemophilia and inhibitors, and has been found to control hemorrhage associated with severe trauma and surgery in patients with basically normal hemostatic mechanisms from the start. By enhancing the generation of thrombin on activated platelets, rFVIIa facilitates the formation of a tight, stable fibrin plug that is resistant to premature lysis. Clinical efficacy has been achieved with doses of rFVIIa much lower than originally proposed by in vitro models. Based on early clinical experiences, a dosing schedule of 90 to 120 microg/kg every 2 hours for the first 24 hours was recommended for serious bleeds and surgical cover. This schedule has been shown to induce and maintain hemostasis in 83% to 95% of serious bleeding episodes, and in 90% to 100% of major surgical cases. However, "mega" doses of rFVIIa may demonstrate greater efficacy in the treatment of joint bleeds, as they are more likely to evoke a full thrombin burst. Interpatient variation in recovery rates, clearance rates, and the ability to generate thrombin on the activated platelet surface may influence the efficacy of rFVIIa. Optimal doses may thus vary not only between hemophilia patients, but also between patients treated for other bleeding disorders.