Fibrinogen coagulation cascade

Induction of the blood coagulation cascade. This culminates in the conversion of a soluble serum protein, fibrinogen, into insoluble fibrin. Fibrin monomers then aggregate at the site of... 

Physiologically, the maintenance of blood circulating freely in the vascular system reflects a meticulous balance between coagulation and fibrinolysis. After microvascular injury subendothelial structures are exposed to which platelets adhere. This is followed by their aggregation and activation of the coagulation cascade with the ultimate conversion of fibrinogen to fibrin. 

In the coagulation cascade (Figure 1), a highly amplified process leads to the formation of thrombin, which is the primary mediator for the conversion of fibrinogen to fibrin, as well as activation of platelets through the thrombin... 

The blood coagulation cascade. Each of the curved red arrows represents a proteolytic reaction, in which a protein is cleaved at one or more specific sites. With the exception of fibrinogen, the substrate in each reaction is an inactive zymogen except for fibrin, each product is an active protease that proceeds to cleave another member in the series. Many of the steps also depend on interactions of the proteins with Ca2+ ions and phospholipids. The cascade starts when factor XII and prekallikrein come into contact with materials that are released or exposed in injured tissue. (The exact nature of these materials is still not fully clear.) When thrombin cleaves fibrinogen at several points, the trimmed protein (fibrin) polymerizes to form a clot. 

Heparin acts indirectly at multiple points within the coagulation cascade, Its major anticoagulant effect is via interaction with its requisite co-factor, antithrombin III (AT). The heparin-AT complex inactivates factors IXa, Xa, and XIla, and binds thrombin at its active site to prevent the conversion of fibrinogen to fibrin (3). Heparin also prevents fibrin stabilization through the inhibition of fibrin stabilization factor. Heparin has no fibrinolytic activity and therefore is ineffective as a thrombolytic (4,5). 

Role of fibrin Local stimulation of the coagulation cascade by factors released from the injured tissue and platelets results in the formation of thrombin (Factor II). In turn, thrombin, a serine protease, catalyzes the conversion of fibrinogen to fibrin, which is incorporated into the plug. Subsequent cross-linking of the fibrin strands stabilizes the clot and forms a hemostatic plug. 

Thrombin (factor Ha) is the last enzyme protease involved in the coagulation cascade, and it converts fibrinogen to insoluble fibrin that forms the fibrin gel either in physiological conditions or in a pathological thrombus (28). Thrombin has also hormonelike properties, and it is involved in thrombosis and platelet activation. Therefore, thrombin plays a central role in a number of cardiovascular diseases (29), and it is thought to regulate many processes in inflammation and tissue repair at the vessel wall. 

---