Antithrombotic properties of dermatan sulphate in a rat venous thrombosis model

It has been suggested that glycosaminoglycans (GAG) such as heparan sulphate (HS), dermatan sulphate (DS), chondroitin-4-sulphate and chondroitin-6-sulphate contribute to the nonthrombogenic properties of the vascular wall. We have investigated the potential role of DS and HS as antithrombotic agents in an experimental model of stasis-induced venous thrombosis in rats. We utilized a range of doses of both DS and HS (0.25-4 mg/kg BW) to test both their antithrombotic activity and potential bleeding effects. The results were evaluated with reference to an unfractionated heparin (0.5-2 mg/kg BW). We report that the antithrombotic activity of DS is not related to its anticoagulant activity as measured by the activated partial thromboplastin time (APTT), thrombin time (TT) and anti-Xa tests. The dose of DS which was able to inhibit thrombus formation by 70% did not prolong the bleeding time measured using two techniques (template and tail transection); in contrast, with HS a prolongation of both times could clearly be seen. On the other hand, standard unfractionated heparin, at a dose which is equipotent to that of DS in preventing thrombus formation, significantly prolonged the bleeding time. These results suggest that DS may be a useful antithrombotic agent with a lower haemorrhagic effect than heparin, unlike HS which expresses a haemorrhagic risk similar to heparin.