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

Chest. 2012 Feb;141(2 Suppl):e24S-e43S. doi: 10.1378/chest.11-2291.

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.

Publication types

  • Comparative Study
  • Practice Guideline
  • Review

MeSH terms

  • Antithrombins / agonists
  • Chondroitin Sulfates / administration & dosage
  • Chondroitin Sulfates / adverse effects
  • Dermatan Sulfate / administration & dosage
  • Dermatan Sulfate / adverse effects
  • Dose-Response Relationship, Drug
  • Evidence-Based Medicine*
  • Fibrinolytic Agents / administration & dosage*
  • Fondaparinux
  • Heparin / administration & dosage
  • Heparin / adverse effects
  • Heparin, Low-Molecular-Weight / administration & dosage
  • Heparin, Low-Molecular-Weight / adverse effects
  • Heparitin Sulfate / administration & dosage
  • Heparitin Sulfate / adverse effects
  • Hirudins / administration & dosage
  • Hirudins / adverse effects
  • Humans
  • Infusions, Intravenous
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / adverse effects
  • Pipecolic Acids / administration & dosage
  • Pipecolic Acids / adverse effects
  • Polysaccharides / administration & dosage
  • Polysaccharides / adverse effects
  • Practice Guidelines as Topic*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Societies, Medical*
  • Thrombin / antagonists & inhibitors
  • Thrombosis / blood
  • Thrombosis / drug therapy*
  • Thrombosis / prevention & control*
  • United States

Substances

  • Antithrombins
  • Fibrinolytic Agents
  • Heparin, Low-Molecular-Weight
  • Hirudins
  • Peptide Fragments
  • Pipecolic Acids
  • Polysaccharides
  • Recombinant Proteins
  • Dermatan Sulfate
  • Heparin
  • Chondroitin Sulfates
  • Heparitin Sulfate
  • danaparoid
  • Thrombin
  • argatroban
  • Fondaparinux
  • bivalirudin