Characterisation of the anticoagulant properties of a range of structurally diverse sulfated oligosaccharides

In this study, 17 sulfated oligosaccharides were assessed by the activated partial thromboplastin time (APTT) test for their anticoagulant activity an d nine were found to exhibit significant activity. Chain length, monosaccha ride makeup, and linkage all appear to be critical factors in determining a nticoagulant activity, with the most active compounds being five- to sixfol d less potent than unfractionated heparin (UFH). Phosphomannopentaose sulfa te (PI-88), one of the most active sulfated oligosaccharides and a promisin g anticancer drug, was selected for further study. PI-88 gave a more linear APTT dose-response curve and displayed less patient-to-patient variation t han UFH, with its activity being neutralised by protamine sulfate. However, PI-88 showed considerable species-to-species variation in its anticoagulan t effect. It was found that PI-88 acted as an anticoagulant by enhancing th e ability of heparin cofactor II (HCII) to inhibit thrombin, and did not ac t via antithrombin III (AT-III) in either inhibiting Factor Xa or thrombin. PI-88 also mildly prolonged the prothrombin time (PT), whilst it had no pl atelet pro-aggregatory activity, nor did it demonstrate direct fibrinolytic activity. Thus, PI-88 represents a potential antithrombotic agent deservin g further study. (C) 2001 Elsevier Science Ltd. All rights reserved.