The blood coagulation cascade promotes the formation of a Fibrin clot. Following damage of a blood vessel, the extrinsic pathway of coagulation (blue arrows) is initiated by Coagulation Factor III/Tissue Factor (TF) which forms a complex with Coagulation Factor VIIa and phospholipid, in the presence of Ca2+ , to activate Coagulation Factor Xa and rapidly generate Thrombin (IIa). Thrombin cleaves Fibrinogen to produce Fibrin which polymerizes in the presence of Coagulation Factor XIIIa to form a Fibrin clot. The slower, intrinsic pathway of coagulation (green arrows) provides an alternate mechanism for activation of Coagulation Factor Xa. It is initiated by Coagulation Factor XII, Plasma Kallikrein, and high molecular weight Kininogen binding to damaged subendothelial tissue. This results in the cleavage and activation of Coagulation Factor XIIa, which activates Coagulation Factor XIa. This factor then cleaves and activates Coagulation Factor IXa. Coagulation Factor IXa, along with Coagulation Factor VIIIa, activates Coagulation Factor Xa. Events downstream of the activation of Factor Xa are common to both the intrinsic and extrinsic pathways of coagulation (orange arrows). Activated Factor Xa cleaves Prothrombin to generate active Thrombin (IIa) which can then cleave Fibrinogen to produce Fibrin monomers. These monomers are cross-linked by Factor XIIIa to form a Fibrin clot.
