Recombinant coagulation factor VIIa: from the concept to clinical application in hemophilia treatment in 2000.

Abstract

The development of factor VIII and factor IX concentrates markedly improved the management of hemophilia A and B and made home therapy possible. However, treatment of hemophilic patients with acquired inhibitors remained difficult. The preparation of prothrombin complex concentrates, nonactivated or activated, addressed this difficult clinical problem, but their use was associated with serious side effects. Factor VIIa was found to be a safer treatment modality. Factor VIIa per se is inactive and needs tissue factor (TF) to become biologically active. TF serves as the receptor for factor VIIa. TF is expressed from vessel walls only upon injury. Treatment of inhibitor patients with plasma-derived factor VII was found to be successful. This led to the development of recombinant factor VIIa, which was also found to be successful in managing hemophilia patients with inhibitors. Up to this point, large numbers of patients have been treated and few serious side effects have been noted. Because of its unique effects on the hemostasis system, recombinant factor VIIa will be useful for other indications as well, including patients with congenital factor VII deficiency, patients with bleeding and liver function impairment, patients with quantitative and qualitative platelet defects, and individuals who have sustained multiple trauma. The development of recombinant factor VII is reviewed in detail.