Chapter: Modern Pharmacology with Clinical Applications: Anticoagulant, Antiplatelet, and Fibrinolytic (Thrombolytic) Drugs

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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 for-mation of thrombin (factor IIa), and the conversion by thrombin of the soluble plasma protein fibrinogen into insoluble fibrin.

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 for-mation of thrombin (factor IIa), and the conversion by thrombin of the soluble plasma protein fibrinogen into insoluble fibrin. The extrinsic pathway appears to be im-portant for initiating fibrin formation, while the intrin-sic pathway is involved in fibrin growth and mainte-nance; both systems constitute the coagulation cascade. This series of linked and overlapping reactions involves conversion of proenzymes (designated by roman nu-merals) into serine proteases (designated by roman nu-meral followed by the suffix -a), and cofactors that speed the protease reactions (factors Va and VIIa).


Exposure of blood to tissue factors activates the ex-trinsic 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 forma-tion. 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 ac-celerate the reactions. 

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