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.