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(Circulation. 2004;110:I-19 – I-26.)
© 2004 American Heart Association, Inc.

Treatment of Venous Thromboembolism

New Anticoagulants for Treatment of Venous Thromboembolism

Jeffrey I. Weitz, MD, FRCP(C), FACP, FCCP

From McMaster University and Henderson Research Centre, Hamilton, Ontario, Canada.

Correspondence to Dr Jeffrey I. Weitz, Henderson Research Centre, 711 Concession Street, Hamilton, Ontario, Canada, L8V 1C3. E-mail jweitz{at}thrombosis.hhscr.org

Treatment of venous thromboembolism (VTE) usually starts with concomitant administration of heparin or low-molecular-weight heparin (LMWH) and a vitamin K antagonist. The parenteral anticoagulant, which is given for at least 5 days, is stopped once the vitamin K antagonist produces a therapeutic level of anticoagulation. Although the introduction of LMWH has simplified the initial treatment of VTE, problems remain. LMWH must be given by daily subcutaneous (SC) injection and vitamin K antagonists require routine coagulation monitoring, which is inconvenient for patients and physicians. Recently, 3 new anticoagulants have been introduced in an attempt to overcome these limitations. These include fondaparinux and idraparinux, synthetic analogs of the pentasaccharide sequence that mediates the interaction of heparin and LMWH with antithrombin, and ximelagatran, an orally active inhibitor of thrombin. These agents produce a predictable anticoagulant response; thus, routine coagulation monitoring is unnecessary. Because they do not bind to platelets or platelet factor 4, fondaparinux and idraparinux do not cause heparin-induced thrombocytopenia (HIT). Unlike vitamin K antagonists, ximelagatran has a rapid onset of action, thereby obviating the need for concomitant administration of a parenteral anticoagulant when starting treatment. The lack of an antidote for these new agents is a drawback, particularly for idraparinux, which has a long half-life.

Key Words: venous thromboembolism • pulmonary embolism • deep venous thrombosis • anticoagulants • coagulation • pharmacology • thrombosis