Partially N-desulfated heparin as a non-anticoagulant heparin: Some physico-chemical and biological properties

Abstract A partially N-desulfated preparation of heparin (UFH) obtained by thermally inactivating heparinic acid for 24 hours at 50°C (TIHA) was examined for its physico-chemical and biological properties in vitro and in vivo . TIHA has a molecular weight of 14,700 and 27% remaining N-sulfate groups (UFH = 17,500 ; 100% N-sulfate groups). TIHA has no anticoagulant activity measurable by conventional amidolytic or clotting tests. However, in a rabbit stasis-induced thrombosis model and using two different thrombogenic stimuli (Feiba and PCC(Konyne)/RVV), TIHA afforded a dose-dependent (1.0–2.5 mg/kg) protection sufficient to impair thrombosis (UFH : fully effective at 0.13 mg/kg). TIHA did not produce any bleeding at supramaximal antithrombotic dosage in a rat tail bleeding and a rabbit ear blood loss model and it did not augment ADP-induced aggregation of platelets. In contrast, a completely N-desulfated derivative of UFH (Inoue and Nagasawa, Carbohydr. Res. 46, 87–95, 1976) also lacking measurable in vitro activity was completely inactive in vivo . The results in this study suggest that TIHA may be considered as a non-anticoagulant heparin still retaining antithrombotic activity and also with lower haemorrhagic effect than UFH.