VIIa

Factor VIIa (FVIIa) is the activated form of coagulation factor VII, a vitamin K–dependent serine protease produced by the liver. In circulation, factor VII is a single-chain zymogen; it becomes VIIa through proteolytic cleavage. VIIa requires calcium and a phospholipid surface to be active and can bind tissue factor (TF) to form the TF–FVIIa complex, the key initiator of the extrinsic pathway of blood coagulation.

The TF–FVIIa complex rapidly activates factor X to Xa and factor IX to IXa, triggering the downstream cascades that generate thrombin and lead to fibrin clot formation. This complex is considered the principal physiologic trigger that starts coagulation in response to vascular injury. VIIa can participate in amplification reactions as well, but its essential function in vivo is driven by TF-bound activity. The activity of VIIa is modulated by calcium, phospholipids, and regulatory inhibitors, and it is influenced by vitamin K status.

Clinical relevance and applications include the use of recombinant activated factor VII (rFVIIa) as a hemostatic agent. rFVIIa is approved for treatment of bleeding in individuals with congenital factor VII deficiency and for hemophilia patients with inhibitors to factor VIII or IX, with off-label use in other refractory bleeding situations. Potential risks include thromboembolic events, particularly in settings of vascular disease or extensive surgery, so its use requires careful risk assessment and monitoring.