Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair.
Coagulation is essential to haemostasis, the bodyâs physiological response to damaged blood vessels, to slow down, minimise and eventually cease the bleeding. The coagulation process is characterised by a cascade of events which lead to the formation of a blood clot.
The Coagulation Pathways
There are two main pathways that initiate coagulation: the extrinsic pathway and the intrinsic pathway. Both pathways result in the production of factor X, which marks the beginning of the common pathway of coagulation.
The Extrinsic Pathway
The extrinsic pathway is generally the first pathway activated in the coagulation process and is stimulated in response to a protein called tissue factor, which is expressed by cells that are normally found external to blood vessels. However, when a blood vessel breaks and these cells come into contact with blood, tissue factor activates factor VII, forming factor VIIa, which triggers a cascade of reactions that result in the rapid production of factor X.
The Intrinsic Pathway
The intrinsic pathway is activated by injury that occurs within a blood vessel. This pathway begins with the activation of factor XII (Hageman factor), which occurs when blood circulates over injured internal surfaces of vessels. Components of the intrinsic pathway also may be activated by the extrinsic pathway; for example, in addition to activating factor X, factor VIIa activates factor IX, a necessary component of the intrinsic pathway. Such cross-activation serves to amplify the coagulation process.
The Common Pathway
The production of factor X results in the cleavage of prothrombin (factor II) to thrombin (factor IIa). Thrombin then converts fibrinogen (factor I) to fibrin (factor Ia), which forms a mesh-like structure that traps platelets and other blood cells, forming a stable clot. The clot is further strengthened by factor XIII (fibrin-stabilizing factor), which cross-links fibrin molecules.
Fibrinolysis is the process of breaking down fibrin clots, which is necessary to restore normal blood flow and prevent excessive clotting. Fibrinolysis is mediated by plasmin, an enzyme that cleaves fibrin into soluble fragments. Plasmin is derived from plasminogen, a plasma protein that is activated by tissue plasminogen activator (tPA) or urokinase plasminogen activator (uPA). These activators are released from endothelial cells or damaged tissues. Fibrinolysis is regulated by several factors, such as plasminogen activator inhibitor-1 (PAI-1), thrombin-activatable fibrinolysis inhibitor (TAFI), and alpha-2-antiplasmin.
Coagulation disorders are disease states that can result in problems with hemorrhage, bruising, or thrombosis. They can be caused by defects or deficiencies in coagulation factors, platelets, or fibrinolytic system. Some examples of coagulation disorders are hemophilia, von Willebrand disease, disseminated intravascular coagulation (DIC), and thrombophilia. Coagulation disorders can be diagnosed by various tests, such as prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen level, platelet count, and bleeding time. Treatment depends on the type and severity of the disorder and may include transfusion of blood products, administration of clotting factors or anticoagulants, or surgical intervention. [^1^