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The coagulation pathway and target sites for anticoagulant drugs. ^3,18 The coagulation pathway is a cascade of enzymatic conversions, each activating the next enzyme (factor) in the sequence. The final enzyme in this pathway is thrombin (factor IIa), which catalyzes the conversion of fibrinogen to fibrin strands. Warfarin acts by inhibiting synthesis of factors in the liver. In contrast, heparin acts to inhibit factors that have become activated within the bloodstream. Thrombin can be activated by either of 2 pathways. The intrinsic pathway is initiated within the bloodstream by platelet thromboplastin. Heparin influences this pathway by inhibiting factors XIIa, XIa, and IXa, which requires its activity to be monitored using the activated partial thromboplastin time. The extrinsic pathway functions outside the bloodstream, initiated by tissue thromboplastin. This pathway is influenced most by warfarin because it inhibits hepatic synthesis of factor VII, the most essential factor in the extrinsic pathway. Therefore the anticoagulant activity of warfarin must be monitored using the prothrombin time (PT), which is now standardized as the international normalized ratio (INR). Newer agents, commencing with the low-molecular-weight heparins, have greater specificity for inhibiting only factors Xa or IIa (thrombin) within the common pathway and therapeutic monitoring is not required.

The coagulation pathway and target sites for anticoagulant drugs.1,4 The coagulation pathway is a cascade of enzymatic conversions, each activating the next enzyme (Factor) in the sequence. The final enzyme in this pathway is thrombin, also called Factor IIa, which catalyzes the conversion of fibrinogen to fibrin strands. Warfarin (W) acts by inhibiting synthesis of factors in the liver. In contrast, heparin (H) acts to inhibit factors that have become activated within the bloodstream. Thrombin can be activated by either of 2 pathways. The intrinsic pathway is initiated within the bloodstream by platelet thromboplastin. H influences this pathway by inhibiting Factor IXa. However, it also inhibits Factors Xa and IIa within the common pathway, and its activity must be monitored using the activated partial thromboplastin time (aPTT). The extrinsic pathway functions outside the bloodstream, initiated by tissue thromboplastin. This pathway is influenced most by W because it inhibits hepatic synthesis of Factor VII, the most essential factor in this pathway. The anticoagulant activity of W is monitored using the prothrombin time (PT), which is now standardized as the international normalized ratio (INR). Newer agents, commencing with the low–molecular-weight Hs (L) have greater specificity for inhibiting Factor Xa and thrombin within the common pathway and generally do not require therapeutic monitoring.

Classic coagulation cascade model featuring the extrinsic, intrinsic, and common coagulation pathways.

Contemporary coagulation model demonstrating the 3 phases: activation (A-C), amplification (D-F), and clot propagation (G). ³