Intrinsic pathway / contact activation pathway
This pathway is named as such because the activation is initiated within the vascular system. It is initiated by the activation of an inactive enzyme (Factor XII) by binding it to a negatively charged surface leading to conversion into the active enzyme (Factor XIIa). This sequence is followed by the activation of Factors IX, X and XI; and the series of activation ends up by converting prothrombin ( Factor II) into thrombin (Factor IIa), which then converts fibrinogen into fibrin which subsequently becomes crosslinked via FXIIIa.
The extrinsic pathway / tissue factor pathway
The extrinsic pathway or tissue factor pathway involves the transmembrane protein thromboplastin, a tissue factor (TF) from the subendothelial matrix. Its exposure to blood cells activates Factor VII and form Factor VIIa, and with phospholipids and Ca2+, activate Factor IX; and that in turn, activate Factor X.
The common pathway – thrombin and fibrin formation
Both pathways lead to the activation of Factor X to Factor Xa. It is from this part of cascade to the final formation of the stable fibrin clot that is named the common pathway. Factor Xa, together with Factor Va, the phospholipid surface of platelets and Ca2+ forms the prothrombinase complex. This complex activates prothrombin (Factor II) to thrombin (Factor IIa). Of the many activities of thrombin, its primary action relates to the final stage of clotting, which is the conversion of the soluble form of fibrinogen to the insoluble fibrin. But thrombin also leads to activation of other coagulation factors, thus supporting the thrombin burst. Thrombin also activates TAFI (thrombin activated fibrinolysis inhibitor) and activates the fibrin stabilizing Factor XIII. Factor XIIIa is an important component in the final stages of the clotting cascade. This factor is cross-linking fibrin and supports the formation of a three dimensional network that include the activated platelets and red blood cells.