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

被引:694
作者
Garcia, David A. [1 ]
Baglin, Trevor P. [2 ]
Weitz, Jeffrey I. [3 ,4 ]
Samama, Meyer Michel [5 ]
机构
[1] Univ New Mexico, Albuquerque, NM 87131 USA
[2] Addenbrookes Hosp, Cambridge Univ Hosp NHS Trust, Cambridge, England
[3] Thrombosis & Atherosclerosis Res Inst, Hamilton, ON, Canada
[4] McMaster Univ, Hamilton, ON, Canada
[5] Hotel Dieu Univ Hosp, Paris, France
关键词
LOW-MOLECULAR-WEIGHT; PARTIAL THROMBOPLASTIN TIME; HEPARIN-INDUCED THROMBOCYTOPENIA; ANTI-FACTOR-XA; ACUTE MYOCARDIAL-INFARCTION; RECOMBINANT FACTOR VIIA; DEEP-VEIN THROMBOSIS; PATHOLOGISTS CONFERENCE XXXI; ACUTE VENOUS THROMBOEMBOLISM; UNFRACTIONATED HEPARIN;
D O I
10.1378/chest.11-2291
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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 fi xed 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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收藏
页码:E24S / E43S
页数:20
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