Antithrombotic and bleeding effects of glycosaminoglycans with different degrees of sulphation

We recently reported that the in vitro anticoagulant activities of dermatan sulphate and heparan sulphate were improved with increased sulphation. In this study we determined how the degree of sulphation of glycosaminoglycans influences their antithrombotic and bleeding effects in vivo. We compared the antithrombotic effects of each glycosaminoglycan by measuring their ability to inhibit experimentally-induced thrombus formation in rabbit jugular veins. The bleeding effect of each glycosaminoglycan was measured by comparing their ability to increase the amount of 51Cr-blood lost from five standardized cuts in rabbit ears. Increased sulphation only improved the antithrombotic effects of dermatan sulphate and heparan sulphate. In contrast, increased sulphation enhanced the blood loss associated with all the glycosaminoglycans evaluated. We conclude that the antithrombotic effects of heparan sulphate and dermatan sulphate can be enhanced by increased sulphation, but that the improved antithrombotic effects are compromised by the concomitant increase in bleeding side-effects.