Fucosylated chondroitin sulfate is a
glycosaminoglycan from sea cucumber, made up of alternating beta-D-
glucuronic acid and N-acetyl-beta-D-
galactosamine units, like mammalian
chondroitin sulfate. But the beta-D-
glucuronic acid residues have branches of sulfated
fucose, which confer high
anticoagulant and antithrombotic properties on this compound. We have now compared the
anticoagulant,
bleeding and antithrombotic effects of this
fucosylated chondroitin sulfate and its carboxyl-reduced derivative. Both compounds have similar
anticoagulant action, mostly due to acceleration of
thrombin inhibition in the presence of
heparin cofactor II. The native
glycosaminoglycan shows a correlation among
anticoagulant,
bleeding and antithrombotic effects. Inhibition of
thrombosis in an arterio-venous shunt occurs at low doses, which are almost ineffective in modifying the
anticoagulant activity of plasma. In a venous experimental model, on the contrary, antithrombotic activity requires high doses and occurs concomitantly with an increase in the
anticoagulant activity of plasma. The action of
fucosylated chondroitin sulfate on
thrombosis is apparently unrelated to its effect on platelet aggregation. The carboxyl-reduced derivative of
fucosylated chondroitin sulfate prevented
thrombosis in the arterio-venous shunt, but not in the venous experimental model. This derivative did not increase
bleeding, in spite of its potent
anticoagulant activity. Therefore, our results reveal a dissociation of the
anticoagulant,
bleeding and antithrombotic effects of the
glycosaminoglycan. Furthermore, we demonstrate that a
polysaccharide may be a potent inhibitor of one type of thrombotic episode, but inactive on another. We propose that the different effects of
fucosylated chondroitin sulfate and its carboxyl-reduced derivative on
venous thrombosis may be related to adherence of the
glycosaminoglycan to the vessel wall.