Blood Coagulation and Blood Coagulation Tests
Blood coagulation, also called blood clotting, is the term given to a complex series of reactions that results in the formation of a tightly knit meshwork at the site where a blood vessel has been severed. The ability of a body to stem the flow of blood following injury to blood vessel is vital to survival of the organism.
Coagulation is a complex process that involves blood cells called platelets, various coagulation factors that are circulating in the blood and blood vessels. When a blood vessel is cut open, the open end shrinks in size to limit the opening. Platelets are recruited to the site to plug the opening. Then, the various enzymatic coagulation factors in the blood plasma are activated, leading to the formation of fibrin. Fibrin is a strong, cross-linked protein that becomes an integral part of the clot.
The coagulation process is actually a cascade, where one reaction initiates another reaction, and so on, until the tightly cross-linked fibrin polymer is formed. The cascade of reaction consists of two pathways, the intrinsic pathway and the extrinsic pathway. One or the other can be initiated depending on the extent of an injury. The extrinsic pathway is triggered by tissue injury while the intrinsic pathway is not. The two pathways do converge at a common point, where a clotting factor called X is converted to Xa. The pathways are complex. There are over 20 proteins, or clotting factors, which must be activated in a set sequence for clotting to be successful. Other components, such as calcium ion, also need to be present for activation (change) of factors
The activated factor Xa, in turn, catalyzes the activation of a protein called prothrombin to form thrombin. Thrombin converts fibrinogen to fibrin. It is at this point that coagulation nears completion. The body tightly controls the concentration of thrombin, as too much circulating thrombin would cause coagulation of blood in areas other than at a cut. This could be lethal. A series of feedback mechanisms is operative throughout the coagulation cascade to put the system in readiness for rapid response to injury.
Another aspect of coagulation is the dissolution of the clot over time, as the injury to the vessel is repaired. Degradation of fibrin clots is due to an enzyme called plasmin. Plasmin results from several activation steps involving several proteins. The degradation pathway is also under tight control. The whole process of coagulation and degradation is called hemostasis. Defects in hemostasis cause bleeding disorders. Examples include hemophilia and von Willebrand Disease.
Coagulation tests can reveal whether the clotting process is proceeding normally or abnormally. The time for blood to clot at room temperature and the physical appearance of the resulting clot is one such test. The number and shape of red blood cells and platelets is determined by light scattering or the change in electrical resistance as blood streams through a small hole. Tests of platelet function, namely aggregation, are visually based tests. Assays also examine the performance of some of the clotting factors, including thrombin. In a test called template bleeding time, a pressure cuff is fitted onto an arm and inflated to restrict blood flow through arm vessels. A small cut is deliberately made and the time for clotting to occur is determined, normally 2-9 minutes. The efficiency of clot formation can be measured in a test tube by lowering a pin coated with platelets into activated whole blood. Fibrin strands interact with the platelets and as a clot forms the pin moves. The pattern of pin movement can be related to the progress of coagulation. Monitoring the pin's motion on a computer can be diagnostic of abnormalities in blood coagulation. The apparatus is called a Thromboelastograph.
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