DHG, A NEW DEPOLYMERIZED HOLOTHURIAN GLYCOSAMINOGLYCAN, EXERTS AN ANTITHROMBOTIC EFFECT WITH LESS BLEEDING THAN UNFRACTIONATED OR LOW-MOLECULAR-WEIGHT HEPARIN, IN RATS

We characterized the antithrombotic, haemorrhagic, and ex vivo anticoa gulant effects of a recently identified depolymerized holothurian glyc osaminoglycan (DHG), and compared these effects with those of unfracti onated heparin (UFH), low molecular weight heparin (LMWH), and dermata n sulfate (DS). In thrombin-induced venous thrombus formation in rats, DHG had a significant preventive effect at 0.3 mg/kg or more at 5 min after i.v. administration. UFH, LMWH, and DS also showed a significan t antithrombotic effect at 0.3, 0.3, and 1 mg/kg, respectively, under the same experimental conditions. After rat tail transection, DHG, UFH , LMWH, and DS prolonged the bleeding time significantly at 10, 1, 1, and 10 mg/kg, respectively, at 5 min after i.v. injection. Therefore, DHG exerts its antithrombotic effect with less bleeding than UFH and L MWH in experimental animals. DHG prolonged the activated partial throm boplastin time in a dose-dependent manner at 0.3-3 mg/kg, at which dos e an antithrombotic effect was exhibited without any significant haemo rrhagic effect. All of these glycosaminoglycans prolonged thrombin clo tting time markedly at their haemorrhagic doses. Copyright (C) 1996 El sevier Science Ltd.