Document Detail


Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
MedLine Citation:
PMID:  22315264     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
David A Garcia; Trevor P Baglin; Jeffrey I Weitz; Meyer Michel Samama;
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Publication Detail:
Type:  Comparative Study; Journal Article; Practice Guideline; Review    
Journal Detail:
Title:  Chest     Volume:  141     ISSN:  1931-3543     ISO Abbreviation:  Chest     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-08     Completed Date:  2012-04-13     Revised Date:  2013-04-08    
Medline Journal Info:
Nlm Unique ID:  0231335     Medline TA:  Chest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e24S-43S     Citation Subset:  AIM; IM    
Affiliation:
University of New Mexico, MSC07-4025, Albuquerque, NM 87131, USA. davgarcia@salud.unm.edu
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MeSH Terms
Descriptor/Qualifier:
Antithrombins / agonists
Chondroitin Sulfates / administration & dosage,  adverse effects
Dermatan Sulfate / administration & dosage,  adverse effects
Dose-Response Relationship, Drug
Evidence-Based Medicine*
Fibrinolytic Agents / administration & dosage*
Heparin / administration & dosage,  adverse effects
Heparin, Low-Molecular-Weight / administration & dosage,  adverse effects
Heparitin Sulfate / administration & dosage,  adverse effects
Hirudins / administration & dosage,  adverse effects
Humans
Infusions, Intravenous
Peptide Fragments / administration & dosage,  adverse effects
Pipecolic Acids / administration & dosage,  adverse effects
Polysaccharides / administration & dosage,  adverse effects
Practice Guidelines as Topic*
Recombinant Proteins / administration & dosage,  adverse effects
Societies, Medical*
Thrombin / antagonists & inhibitors
Thrombosis / blood,  drug therapy*,  prevention & control*
United States
Chemical
Reg. No./Substance:
0/Antithrombins; 0/Fibrinolytic Agents; 0/Heparin, Low-Molecular-Weight; 0/Hirudins; 0/Peptide Fragments; 0/Pipecolic Acids; 0/Polysaccharides; 0/Recombinant Proteins; 128270-60-0/bivalirudin; 24967-94-0/Dermatan Sulfate; 74863-84-6/argatroban; 83513-48-8/danaproid; 9005-49-6/Heparin; 9007-28-7/Chondroitin Sulfates; 9050-30-0/Heparitin Sulfate; EC 3.4.21.5/Thrombin; J177FOW5JL/fondaparinux
Comments/Corrections
Erratum In:
Chest. 2012 May;141(5):1369
Note: Dosage error in article text

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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