Unbalanced effects of dermatan sulfates with different sulfation patterns on coagulation, thrombosis and bleeding

We compared the anticoagulant, antithrombotic and bleeding effects of highl y sulfated dermatan sulfates from invertebrates and their mammalian counter part. An invertebrate dermatan sulfate containing 2-O-sulfated alpha -L-idu ronic acid and 4-O-sulfated N-acetyl-beta -D-galactosamine residues is a po tent anticoagulant due to a high heparin cofactor II activity. It inhibits thrombin due to the formation of a covalent complex with heparin cofactor I I, as in the case of mammalian dermatan sulfate, but the effect occurs at l ower concentrations for the invertebrate polysaccharide, Surprisingly, the invertebrate dermatan sulfate has a lower potency to prevent thrombus forma tion on an experimental model and a lower bleeding, effect in rats than the mammalian dermatan sulfate. In contrast, another invertebrate dermatan sul fate, also enriched in 2-O-sulfated alpha -L-iduronic acid, but in this cas e sulfated at O-6 position of the N-acetyl-beta -D-galactosamine units, has no in vitro or in vivo anticoagulant activity, does not prevent thrombus f ormation but shows a bleeding effect similar to the mammalian glycosaminogl ycan. Overall, these results demonstrate unbalanced effects of dermatan sul fates with different sulfation patterns on coagulation, thrombosis and blee ding, and raise interesting questions concerning the relationship among the se three biological actions of sulfated polysaccharides.