Platelet binding and activity of recombinant factor VIIa

Recombinant FVIIa was developed for the purpose of treating hemophiliacs with antibody inhibitors. It was initially assumed to act by enhancing factor X activation by a tissue factor-dependent mechanism. However, the very high levels of FVIIa required for hemostatic effect in vivo seemed inconsistent with this mechanism. After many years of debate, in now appears that platelet surface binding and activity play an important role in the efficacy of FVIIa as a bypassing agent in hemophilia. Platelet binding was initially suggested to be mediated by binding to anionic phospholipid exposed on platelet surfaces upon activation. It now appears that the glycoprotein Ib/IX/V complex also plays a role in FVIIa binding to platelets. However, the characteristics of FVIIa binding to GPIb/IX/V to not seem to fully explain platelet localization of FVIIa to platelets. Thus, there are still unanswered questions in fully understanding the mechanism of hemostatic action of recombinant FVIIa.