Rationale for Targeting Factor Xa and Thrombin

Two key pharmacologic targets within the coagulation cascade are factor Xa and factor IIa (thrombin). Table 1 lists several agents, some established, some in development (names italicized), that inhibit factor Xa or IIa (or both), either indirectly through antithrombin (AT; formerly, antithrombin III) or directly (AT-independent). The rationale for targeting these factors follows from their key roles in coagulation. Factor X is synthesized by the liver in a vitamin K-dependent manner. Positioned at the start of the final common pathway, factor X is activated by both the extrinsic tenase complex (VIIa/TF) and the intrinsic tenase complex (IXa/VIIIa); the resulting factor Xa (a serine protease) then forms the prothrombinase complex with factor Va and ionic calcium on membranes, catalyzing the conversion of prothrombin to

TABLE 1 Parenteral and Oral Anticoagulants that Directly or Indirectly Block Thrombin or Factor Xa
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