The coagulation cascade of secondary hemostasis has two pathways (the Contact Activation pathway and the Tissue Factor pathway) that lead to fibrin formation. It was previously thought that the coagulation cascade consisted of two pathways of equal importance joined to a common pathway. It is now known that the primary pathway for the initiation of blood coagulation is the Tissue Factor pathway. The pathways are a series of reactions, in which a zymogen of a serine protease and its glycoprotein co-factor are activated to become active components that then catalyze the next reaction in the cascade. Coagulation factors are generally indicated by Roman numerals, with a lowercase a appended to indicate an active form, ultimately resulting in cross-linked fibrin.
Formation of the primary complex on collagen by high molecular weight kininogen (HMWK), prekallikrein and Factor XII (Hageman factor), prekallikrein is converted to kallikrein and Factor XII becomes Factor XIIa. Factor XIIa converts Factor XI into Factor XIa. Factor XI is also activated by Factor VIIa. Factor IX is in turn activated by Factor XIa which with its co-factor Factor VIIIa form the tenase complex which activates Factor X to Factor Xa. The minor role that the contact activation pathway has in initiating clot formation can be illustrated by the fact that patients with severe deficiencies of Factor XII, HMWK and prekallikrein do not have a bleeding disorder. Thrombin has a large array of functions. Its primary role is the conversion of fibrinogen to fibrin, the building block of a hemostatic plug. In addition, it activates Factors VIII and Factor V and their inhibitor protein C (in the presence of thrombomodulin), and it activates Factor XIII, which forms covalent bonds that crosslink the fibrin polymers that form from activated monomers. Following activation by the contact factor or tissue factor pathways the coagulation cascade is maintained in a prothrombotic state by the continued activation of Factor VIII and Factor X to form the tenase complex, until it is down regulated by the anticoagulant pathways.
The main role of the tissue factor pathway is to generate a "thrombin burst". Thrombin being the single most important constituent of the coagulation cascade in terms of its feedback activation roles. Factor VIIa circulates in a higher amount than any other activated coagulation factor and following damage to the blood vessel endothelium Tissue Factor (TF) is released, this then forms a complex with Factor VIIa (TF-FVIIa) this activates Factor IX and Factor X. Factor VII itself is activated by thrombin, Factor XIa, plasmin, Factor XII and Factor Xa. The activation of Factor Xa by TF-FVIIa is almost immediately inhibited by tissue factor pathway inhibitor (TFPI). Factor Xa and its co-factor Va form the prothombinase complex which activates prothrombin to thrombin. Thrombin then activates other components of the coagulation cascade, including Factor V and Factor VII (which activates Factor XI which in turn activates Factor IX), and activates and releases Factor VIII from being bound to vWF. Factor VIIIa is the co-factor of Factor XIa and together they form the "tenase" complex which activates Factor X and so the cycle continues.
The coagulation factors are serine proteases (enzymes) except Factor VIII and Factor V which are glycoproteins. The serine proteases act by cleaving other proteins at specific sites. Factor XIII is a transglutaminase. Protein C is also a serine protease.
DiaPharma has dozens of graphical representations of the coagulation cascade in our Illustrations section.
Sources: DiaPharma, Wikipedia