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עמוד בית
Sat, 20.07.24

Reviews

IMAJ | volume

Journal 8, August 2004
pages: 479-481

New Trends in Anticoagulant Therapy

    Summary

    Classic anticoagulant drugs, such as heparin and warfarin, are very effective. Although in use for more than 50 years, they have some clinical drawbacks. Heparin, now better termed unfractionated heparin, can only be used intravenously and its laboratory control is complicated. Warfarin is orally administered, but its therapeutic window is very narrow and patients need repeated laboratory tests. Moreover, both drugs are non-specific, as they inhibit the coagulation cascade at several steps. Pharmaceutic research has developed new drugs, some of which are already on the market, such as fondaparinux, a pentasaccharide that can interact with antithrombin, thus inhibiting factor Xa. This pentasaccharide is part of the parent heparin molecule and can be chemically synthesized, with the advantage of avoiding extractive compounds. Fondaparinux has a half-life compatible with once-a-day administration; modification of its structure (idraparinux) has led to more stable binding with antithrombin and to an increase in its half-life to allow once-a-week administration. Alternatives to oral anticoagulants have been developed following the study of some compounds like hirudin, which directly binds thrombin and blocks its catalytic site. One of these molecules, ximelagatran, is in advanced clinical development. Ximelagatran is converted into its active form, melagatran, in the circulation, and thrombin activity can be blocked by oral administration twice daily. There is no need for laboratory control and phase II and phase III studies are encouraging. The next few years should bring great changes in the treatment of patients with thromboembolic disorders.

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