ABSTRACT
INTRODUCTION Progress in Drug Development Historical approaches to anticoagulation have relied on partially purifi ed or chemically derivatized natural products, such as heparin and warfarin (Hirsh et al., 2007). The utility of these agents, however, is limited by interpatient variability in pharmacologic effect, the requirement for routine coagulation monitoring, and, for warfarin, various food and drug interactions. The association of heparin and warfarin with prothrombotic complications-immune heparin-induced thrombocytopenia (HIT), and warfarin necrosis-is particularly troublesome. Low molecular weight heparin (LMWH) has replaced heparin for many indications because LMWH produces a more predictable anticoagulant effect and is associated with a lower risk of HIT. The parenterally administered selective factor Xa inhibitor, fondaparinux, represents a further advance over LMWH, and since the last edition of this book has emerged as a viable —albeit nonapproved (“off-label”)— treatment for HIT. Several new orally administered anticoagulants that selectively target factor IIa (thrombin) or factor Xa have now been approved for (non-HIT) clinical use and in the future may also be attractive options for the treatment of HIT.
