Further Understanding of Recombinant Activated Factor VII Mode of Action

Recombinant activated factor VII (rFVIIa) is being increasingly used to treat bleeding associated with a variety of non-hemophilic coagulopathic indications, and its mechanism of action in these areas is under active investigation. Numerous studies have shown that FVIIa binds with low affinity to activated platelets; rFVIIa can subsequently enhance platelet-surface thrombin generation by activating factor (F) X and by contributing additional FIXa to the hemostatic process. This FIXa can rapidly activate additional FX, which may explain why non-hemophilic coagulopathic bleeds respond to lower doses of rFVIIa than do hemophilic bleeds. However, the platelet surface may be able to process only a limited amount of FXa, accounting for the observation that some models of non-hemophilic coagulopathy show a plateau in the effect of rFVIIa.