Coagulation Cascade
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Introduction
- The arrest of bleeding depends upon primary platelet plug formation in conjunction with the elaboration of a stable fibrin clot. In the interim, vasoconstriction reduces blood flow through injured vessels. Formation of the fibrin clot involves the sequential interaction of a series of plasma proteins in an ordered fashion, as well as interactions of these proteins with platelets & with materials released from tissues.
- The coagulation cascade is a process of signal amplification subject to inhibitory constraints. Specific extravascular membrane proteins* serve as receptors for zymogens & cofactors involved in coagulation. This triggers a cascade of events leading to the formation & cross-linking of fibrin. In the absence of a sufficient quantity of initiating factors, inhibitory mechanisms predominate & coagulation is suppressed.
- The coagulation cascade is initiated when endothelium is injured, resulting in exposure of tissue factor ( TF) constitutively expressed on the cell surface of subendothelial cells such as smooth muscle cells & fibroblasts. TF complexes with circulating coagulation factor VII resulting in an activated TF/VIIa complex (see extrinsic pathway).
- Propagation occurs from TF/VIIa - catalyzed activation of factor IX & the intrinsic pathway. Thrombin also contributes to propagation. Coagulation centers around formation of thrombin. When small amounts of thrombin are formed, or when thrombin is diluted by a fast flowing circulation, thrombin acts as a platelet agonist initiating & enhancing platelet aggregation through the action of thrombin receptors on the surface of platelets. However, in static zones of flow (presumably secondary to prior platelet aggregation), thrombin will accumulate & convert fibrinogen into fibrin in the surrounding blood.
- Thus, the interrelationships between platelet function (activation, adhesion & aggregation) & coagulation ( clotting) are complex, & it is not possible to conceive of one without the other.
More General Terms
Additional Terms
Internet Database
Kegg: [1]
References
Clinical Diagnosis & Management by Laboratory Methods, 19th edition, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1996, pg 719
