Tissue factor (TF)
TF is a transmembrane glycoprotein receptor found in extravascular tissues, including organ capsules and the adventitia of blood vessel walls. It is constitutively expressed on fibroblasts and, on cellular activation, on vascular smooth muscle cells, monocytes, and neutrophils. The TF-bearing cells and platelet surfaces act as the main cellular surfaces for assembly of the procoagulant complexes. It is exposed to flowing blood during injury or inflammation, binds FVIIa, and initiates the extrinsic coagulation pathway.
Fibrinogen is proteolytically cleaved to form fibrin, producing a firm clot.
Prothrombin is proteolytically cleaved to form thrombin. Thrombin, in turn, converts fibrinogen to fibrin; activates soluble FV, FVIII, FXI, and FXIII; and binds to thrombomodulin to activate PC.
FV is principally synthesized in the liver and is activated to FVa by FXa and thrombin. FXa associates with its cofactor FVa to form prothrombinase complexes that activate FII (prothrombin) to FIIa (thrombin).
Factor VII binding to TF results in activation to Factor VIIa. Factor VIIa bound to TF on the cell surface activates Factor IX to Factor IXa and Factor X to Factor Xa.
FVIII and von Willebrand factor (vWF) circulate in plasma as a noncovalent bimolecular complex. Upon activation by thrombin, FVIIIa dissociates from the FVIII-vWF complex to interact with FIXa.
FIXa on platelets and TF-bearing cells binds with FVIIIa, assembling the FIXa-FVIIIa complex (intrinsic tenase). The FIXa-FVIIIa complex activates FX.
FX is activated to FXa, the enzyme of the prothrombinase complex that cleaves prothrombin to thrombin.
FXIIa and FXIa interact to activate FIX.
Once bound to TF, the proenzyme FVII is activated to the enzyme FVIIa. The TF-FVIIa complex (extrinsic tenase) activates FX, triggering the intrinsic coagulation pathway (in vitro).
When activated by thrombin, FXIIIa cross-links adjacent fibrin monomers to strengthen and stabilize fibrin clots.
Protein C (PC)
PC is a serine protease that is the precursor to the protease referred to as activated protein C (PCa).
Protein S (PS)
PS is serine protease that is a nonenzymatic cofactor that enhances activity of PCa.
TM is a cell surface receptor for thrombin, mainly expressed on undamaged endothelium. The antithrombic effect of TM involves removal of thrombin escaped from sites of vascular injury.