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.
Published Version
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