Summary

We compared the anticoagulant, antithrombotic and bleeding effectsof highly sulfated dermatan sulfates from invertebrates and theirmammalian counterpart. An invertebrate dermatan sulfate containing2-O-sulfated α-L-iduronic acid and 4-O-sulfated N-acetyl-β-D-galactosamineresidues is a potent anticoagulant due to a high heparin cofactorII activity. It inhibits thrombin due to the formation of a covalentcomplex with heparin cofactor II, as in the case of mammalian dermatansulfate, but the effect occurs at lower concentrations for the invertebratepolysaccharide. Surprisingly, the invertebrate dermatan sulfatehas a lower potency to prevent thrombus formation on an experimentalmodel and a lower bleeding effect in rats than the mammalian dermatansulfate. In contrast, another invertebrate dermatan sulfate, also enrichedin 2-O-sulfated α-L-iduronic acid, but in this case sulfated at O-6 positionof the N-acetyl-β-D-galactosamine units, has no in vitro or in vivoanticoagulant activity, does not prevent thrombus formation but showsa bleeding effect similar to the mammalian glycosaminoglycan. Overall,these results demonstrate unbalanced effects of dermatan sulfateswith different sulfation patterns on coagulation, thrombosis andbleeding, and raise interesting questions concerning the relationshipamong these three biological actions of sulfated polysaccharides.