TFVIIaCa2

TFVIIaCa2, or the tissue factor–VIIa–calcium complex, is a ternary proteolytic complex that forms on phospholipid membranes when tissue factor (TF) encounters circulating factor VIIa (FVIIa) in the presence of calcium ions (Ca2+). TF is a transmembrane glycoprotein that acts as a cofactor for coagulation, and FVIIa is the activated serine protease that initiates proteolysis once bound to TF. Calcium ions stabilize the interaction and help position the complex on an anionic phospholipid surface, such as that provided by activated platelets or damaged endothelium.

TFVIIaCa2 is also known as the extrinsic tenase complex. It cleaves factors X and IX to Xa and IXa, respectively. In doing so, it initiates the common coagulation pathway: Xa, with its cofactor Va, converts prothrombin to thrombin, which then converts fibrinogen to fibrin to form a clot. The complex activity is highly dependent on the phospholipid surface and is augmented on platelet membranes where Ca2+-facilitated substrate alignment occurs.

Regulation and clinical relevance: The TF–FVIIa–Ca2+ activity is regulated by tissue factor pathway inhibitor (TFPI), which inhibits TF–FVIIa and Xa. Anticoagulants such as heparin and antithrombin modulate downstream effects. Pathological TF expression, seen in cancer and inflammatory states, can promote thrombosis, while insufficient TF activity contributes to bleeding risk. Therapeutically, recombinant FVIIa is used to treat bleeding in patients with congenital FVII deficiency or inhibitors to other coagulation factors, illustrating the central role of TFVIIaCa2 in hemostasis and its relevance as a target in anticoagulant strategies.