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      Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

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          Abstract

          This article describes the pharmacology of approved parenteral anticoagulants. These include the indirect anticoagulants, unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), fondaparinux, and danaparoid, as well as the direct thrombin inhibitors hirudin, bivalirudin, and argatroban. UFH is a heterogeneous mixture of glycosaminoglycans that bind to antithrombin via a unique pentasaccharide sequence and catalyze the inactivation of thrombin, factor Xa, and other clotting enzymes. Heparin also binds to cells and plasma proteins other than antithrombin causing unpredictable pharmacokinetic and pharmacodynamic properties and triggering nonhemorrhagic side effects, such as heparin-induced thrombocytopenia (HIT) and osteoporosis. LMWHs have greater inhibitory activity against factor Xa than thrombin and exhibit less binding to cells and plasma proteins than heparin. Consequently, LMWH preparations have more predictable pharmacokinetic and pharmacodynamic properties, have a longer half-life than heparin, and are associated with a lower risk of nonhemorrhagic side effects. LMWHs can be administered once daily or bid by subcutaneous injection, without coagulation monitoring. Based on their greater convenience, LMWHs have replaced UFH for many clinical indications. Fondaparinux, a synthetic pentasaccharide, catalyzes the inhibition of factor Xa, but not thrombin, in an antithrombin-dependent fashion. Fondaparinux binds only to antithrombin. Therefore, fondaparinux-associated HIT or osteoporosis is unlikely to occur. Fondaparinux exhibits complete bioavailability when administered subcutaneously, has a longer half-life than LMWHs, and is given once daily by subcutaneous injection in fixed doses, without coagulation monitoring. Three additional parenteral direct thrombin inhibitors and danaparoid are approved as alternatives to heparin in patients with HIT.

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          Author and article information

          Journal
          Chest
          Chest
          Elsevier BV
          1931-3543
          0012-3692
          Feb 2012
          : 141
          : 2 Suppl
          Affiliations
          [1 ] University of New Mexico, Albuquerque, NM. Electronic address: davgarcia@salud.unm.edu.
          [2 ] Cambridge University Hospitals NHS Trust, Addenbrooke's Hospital, Cambridge, England.
          [3 ] Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON, Canada.
          [4 ] Hotel Dieu University Hospital, Place du Parvis Notre Dame, Paris, France.
          Article
          S0012-3692(12)60118-4
          10.1378/chest.11-2291
          3278070
          22315264
          720ce110-d45f-4875-b9f4-562dc216a703
          History

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