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.
Laboratory for Haemostasis and Thrombosis Research, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
A
A
Maggi
M
M
Abbadini
P G
PG
Pagella
A
A
Borowska
J
J
Pangrazzi
M B
MB
Donati
D000818:Animals; D001760:Bleeding Time; D002807:Chondroitin / Q000031:analogs & derivatives*; D003871:Dermatan Sulfate / Q000627:therapeutic use*; D006497:Heparan Sulfate / Q000627:therapeutic use; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013924:Thrombophlebitis / Q000188:drug therapy*; D014682:Vena Cava, Inferior / Q000473:pathology
D002807:Chondroitin; D003871:Dermatan Sulfate; D006497:Heparan Sulfate