Coagulation Systems

Two interrelated processes, the intrinsic and extrinsic coagulation systems (Fig. 22.1), converge on a common pathway that leads to the activation of factor X, the formation of thrombin (factor IIa), and the conversion by thrombin of the soluble plasma protein fibrinogen into insoluble fibrin. The extrinsic pathway appears to be important for initiating fibrin formation, while the intrinsic pathway is involved in fibrin growth and maintenance; both systems constitute the coagulation cascade. This series of linked and overlapping reactions involves conversion of proenzymes (designated by roman numerals) into serine proteases (designated by roman numeral followed by the suffix -a), and cofactors that speed the protease reactions (factors Va and VIIa).

Exposure of blood to tissue factors activates the extrinsic system, beginning with the proteolytic conversion of factor VII into factor VIIa. Degradation of factors V and VIII:C by protein C at locations distant from the site of vascular injury aids in the localization of clot formation. The coagulation cascade is capable of tremendous amplification as the protease reactions progress. Many of the activated coagulation factors feed back positively in the extrinsic, intrinsic, and common pathways and accelerate the reactions. Either deficiency in a single clotting factor or therapy with the drugs described in this chapter will result in abnormal hemostasis.

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