Antithrombin-independent anticoagulation by hypersulfated low-molecular-weight heparin.

Abstract

Low-molecular-weight heparin (LMWH) inhibits the activity of the intrinsic factor X activation complex, a property that persists when LMWH is rendered low affinity (LA) for antithrombin, but is reduced when it is N-desulfated. When LA-LMWH is hypersulfated (sLA-LMWH), its potency against intrinsic tenase is increased and it acquires inhibitory activity against prothrombinase. sLA-LMWH functions by interfering with the association of enzyme and cofactor in both activation complexes. In a rabbit carotid artery thrombosis prevention model, sLA-LMWH is superior to LMWH. Because of its low affinity for antithrombin and multiple sites of action, sLA-LMWH may prove to be safer and more effective than other anticoagulants.

• Authors: James C Fredenburgh, Julia A M Anderson, Jeffrey I Weitz
• Journal: Trends in cardiovascular medicine (Trends Cardiovasc Med) Vol. 12 Issue 7 Pg. 281-7 (Oct 2002) ISSN: 1050-1738 [Print] United States
• PMID: 12458089 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Anticoagulants
• Antithrombins
• Blood Coagulation Factors
• Heparin, Low-Molecular-Weight
• Neoplasm Proteins
• Cysteine Endopeptidases
• cancer procoagulant

Topics

• Animals
• Anticoagulants (pharmacology, therapeutic use)
• Antithrombins (drug effects, pharmacology, therapeutic use)
• Blood Coagulation (drug effects)
• Blood Coagulation Factors (drug effects)
• Carotid Artery Thrombosis (drug therapy)
• Cysteine Endopeptidases (drug effects)
• Heparin, Low-Molecular-Weight (pharmacology, therapeutic use)
• Humans
• Neoplasm Proteins (drug effects)