The role of cell surfaces and cellular receptors in the mode of action of recombinant factor VIIa

Recombinant factor VIIa (rFVIIa) has been developed to treat bleeding episodes in patients with inhibitor-complicated hemophilia. More recently, it has become apparent that rFVIIa is also useful in a prophylactic setting, although its prophylactic effect with a once-daily administration is difficult to explain given its half life of ~ 2 h. The prohemostatic effects of rFVIIa have been ascribed to enhancement of thrombin generation and various downstream effects thereof. There is an ongoing debate on the tissue factor-dependency of rFVIIa, but accumulating evidence is in favor of a TF-independent mechanism. rFVIIa interacts with cellular surfaces and with various receptors on vascular cells. These interactions may contribute significantly to its mode of action in patients with hemophilia. In this review we will summarize laboratory and clinical evidence on the mode of action of rFVIIa in hemophilia with an emphasis on recent insights regarding the interactions of rFVIIa with cellular receptors.