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Selective inhibition of coagulation factors: advances in antithrombotic therapy.

Heparin and coumarin derivatives have long been used for the prophylaxis and treatment of venous thromboembolism (VTE). Although they have demonstrated efficacy and safety, they act at multiple targets within the coagulation cascade and their efficacy is influenced by many patient variables. Because of the need to improve the benefit-to-risk ratio of antithrombotic drugs, newer agents that target single coagulation factors have been developed. These include selective factor Xa inhibitors, direct thrombin inhibitors (DTIs), and inhibitors of factor IXa and the factor VII-tissue factor complex. Three DTIs-hirudin, bivalirudin, and argatroban-have been approved for clinical use. Fondaparinux, a novel pentasaccharide and the first selective factor Xa inhibitor to be approved by the U.S. Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products, is indicated for the prevention of VTE after major orthopedic surgery. Fondaparinux has predictable pharmacokinetics, is almost 100% bioavailable, and has a half-life that allows once-daily dosing in all indications. In addition, the routine monitoring of standard indicators of hemostasis is not required. The availability of these agents and the continued development of investigational selective coagulation inhibitors have the potential to improve efficacy and decrease adverse events in patients at risk for VTE.