Antithrombin-independent anticoagulation by hypersulfated low-molecular-weight heparin.
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.
Fredenburgh
James C
JC
Henderson Research Centre, Hamilton, Ontario, Canada.
Anderson
Julia A M
JA
Weitz
Jeffrey I
JI
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology* / Q000627:therapeutic use; D000991:Antithrombins / Q000187:drug effects* / Q000494:pharmacology* / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000187:drug effects; D002341:Carotid Artery Thrombosis / Q000188:drug therapy; D003546:Cysteine Endopeptidases / Q000187:drug effects; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009363:Neoplasm Proteins / Q000187:drug effects
D000925:Anticoagulants; D000991:Antithrombins; D001779:Blood Coagulation Factors; D006495:Heparin, Low-Molecular-Weight; D009363:Neoplasm Proteins; D003546:Cysteine Endopeptidases; C030910:cancer procoagulant