| pubmed-article:11562342 | pubmed:abstractText | In this study, 17 sulfated oligosaccharides were assessed by the activated partial thromboplastin time (APTT) test for their anticoagulant activity and nine were found to exhibit significant activity. Chain length, monosaccharide makeup, and linkage all appear to be critical factors in determining anticoagulant activity, with the most active compounds being five- to sixfold less potent than unfractionated heparin (UFH). Phosphomannopentaose sulfate (PI-88), one of the most active sulfated oligosaccharides and a promising anticancer drug, was selected for further study. PI-88 gave a more linear APTT dose-response curve and displayed less patient-to-patient variation than UFH, with its activity being neutralised by protamine sulfate. However, PI-88 showed considerable species-to-species variation in its anticoagulant effect. It was found that PI-88 acted as an anticoagulant by enhancing the ability of heparin cofactor II (HCII) to inhibit thrombin, and did not act 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 platelet pro-aggregatory activity, nor did it demonstrate direct fibrinolytic activity. Thus, PI-88 represents a potential antithrombotic agent deserving further study. | lld:pubmed |
