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Fondaparinux sodium is a synthetic sulfated pentasaccharide developed from the antithrombin binding moiety of heparin. Through the activation of antithrombin, fondaparinux selectively inhibits coagulation factor Xa, which in turn inhibits the activation of thrombin and the subsequent coagulation cascade. The drug binds with high affinity to antithrombin III and catalyzes a conformational change in the serpin's reactive loop, potentiating the natural inhibitory effect of antithrombin against factor Xa by a factor of approximately 300. This potentiation results in effective and dose-dependent inhibition of thrombin generation, whether triggered by intrinsic or extrinsic pathways. Unlike low molecular weight heparins that act on multiple targets within the coagulation cascade, fondaparinux demonstrates selective factor Xa inhibition with no direct activity against thrombin. This selectivity contributes to a favorable tolerability profile, particularly with regard to the risk of major bleeding.
Fig. 1 Mechanism of action of Fondaparinux Sodium. (Robinson D M, Wellington K. 2005)
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