The coagulation cascade is responsible for the formation of a stable fibrin clot. It consists of an integrated cascade of enzyme reactions which amplifies a relatively small stimulus to produce a large response. It is now widely accepted that initiation of the cascade occurs when circulating coagulation factor VII is exposed to tissue factor expressed by the subendothelial tissues at the site of injury. This results in the formation of a tissue factor-factor VIIa complex which, through its actions on factors IX and X, leads to the generation of thrombin (Fig 1). Thrombin cleaves fibrinogen to fibrin, and activates factor XIII and platelets. As well as enhancing clot formation, thrombin also limits coagulation by activating protein C through its interaction with thrombomodulin. Screening tests, such as the prothombin time (PT), activated partial thromboplastin time, and thrombin time, can be used to assess the function of the extrinsic, intrinsic, and thrombin-fibrinogen pathways respectively. Congenital or acquired defects of the major coagulation factors can result in hemorrhage in the brain, gastrointestinal tract, muscles, joints, and soft tissues.
Fig. 1 The coagulation and anticoagulation pathways: TF, tissue factor; TFPI, tissue factor pathway inhibitor. Coagulation is initiated when factors VII or VIIa in plasma come into contact with tissue factor at the site of vascular injury. Limited quantities of factors IXa and Xa are generated before there is feedback inhibition of tissue factor-factor VIIa complex by tissue factor pathway inhibitor in concert with factor Xa. The generation of factor Xa is then amplified through the action of factor VIIIa on factor IXa; the latter is initially produced by tissue factor-factor VIIa complex and supplemented by factor XIa. The mechanism(s) for in vivo factor XI activation remain to be established. The broken lines indicate inhibitory pathways.
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