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Antithrombotic and Thrombolytic Therapy, 8th Ed : ACCP Guidelines: ANTITHROMBOTIC AND THROMBOLYTIC THERAPY, 8TH ED: ACCP GUIDELINES |

Parenteral Anticoagulants*: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)

Jack Hirsh, MD, FCCP; Kenneth A. Bauer, MD; Maria B. Donati, MD, PhD; Michael Gould, MD, FCCP; Meyer M. Samama, MD; Jeffrey I. Weitz, MD, FCCP
Author and Funding Information

*From the Hamilton Civic Hospitals, Henderson Research Centre (Dr. Hirsh), Hamilton, ON, Canada; Beth Israel Deaconess Medical Center (Dr. Bauer), Boston, MA; Centre for High Technology and Education in Biomedical Sciences (Dr. Donati), Catholic University, C.da Tappino, Campobasso, Italy; VA Palo Alto Health Care System (Dr. Gould), Palo Alto, CA; Hôtel-Dieu University Hospital (Dr. Samama), Paris, France; and Henderson Research Centre and McMaster University (Dr. Weitz), Hamilton, ON, Canada.

Correspondence to: Jack Hirsh, MD, FCCP, Henderson Research Centre, 711 Concession St, Hamilton, ON, L8V 1C3, Canada; e-mail: jhirsh@thrombosis.hhscr.org



Chest. 2008;133(6_suppl):141S-159S. doi:10.1378/chest.08-0689
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This chapter describes the pharmacology of approved parenteral anticoagulants, including 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 factors. Heparin also binds to cells and other plasma proteins, endowing it with unpredictable pharmacokinetic and pharmacodynamic properties, and can lead to 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 proteins than heparin. Consequently, LMWH preparations have more predictable pharmacokinetic and pharmacodynamic properties, have a longer half-life than heparin, and have a lower risk of nonhemorrhagic side effects. LMWHs can be administered once or twice daily by subcutaneous injection, without anticoagulant 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, HIT and osteoporosis are unlikely to occur. Fondaparinux has excellent bioavailability when administered subcutaneously, has a longer half-life than LMWHs, and is given once daily by subcutaneous injection in fixed doses, without anticoagulant monitoring. Three parenteral direct thrombin inhibitors and danaparoid are approved as alternatives to heparin in HIT patients.

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