Coagulation factor VIIa (FVIIa) (FVIIa)

Coagulation factor VIIa (FVIIa) is a vitamin K-dependent serine protease that serves as the primary initiator of the extrinsic pathway of blood coagulation when complexed with its integral membrane cofactor, tissue factor (TF) [1, 6]. Under physiological conditions, FVIIa remains largely inactive in circulation until it binds to TF, which is exposed upon vascular injury [2, 13]. The resulting TF:FVIIa complex, also known as the extrinsic tenase complex, catalyzes the activation of factors IX and X, leading to a thrombin burst and the formation of a stable fibrin clot [3, 7, 19]. Beyond hemostasis, the TF:FVIIa complex mediates cellular signaling through the activation of protease-activated receptor 2 (PAR2), influencing inflammation, angiogenesis, and tumor progression [9, 11, 16]. Therapeutically, recombinant FVIIa is used as a bypassing agent to treat bleeding in hemophilia patients with inhibitors and those with congenital FVII deficiency [8, 12, 14]. Conversely, targeting the TF:FVIIa complex with inhibitors is a strategy under investigation for the prevention of thrombosis in cardiovascular disease and cancer, aiming to provide anticoagulation with a reduced risk of bleeding compared to traditional therapies [1, 10, 13]. Notable safety concerns include the risk of serious arterial and venous thrombotic events, such as myocardial infarction and stroke, particularly with high-dose or off-label use [18, 20].

Other names

Activated factor VIIFactor VIIaProconvertinSerum prothrombin conversion acceleratorSPCAF7Extrinsic tenase complex

Initiation of the extrinsic pathway of coagulation by activating factors IX and X; bypassing the intrinsic pathway in hemophilia [2, 19, 20].