Abstract

Orgaran is a mixture of glycosaminoglycans extracted from animal mucosa. It consists of heparan, dermatan and chondroitin sulfate; a small proportion of heparan sulfate (4%) has high affinity for antithrombin III (AT III). Orgaran is devoid of heparin or heparin fragments. Orgaran catalyses the inactivation of factor Xa and thrombin. Compared to heparin and most low-molecular-weight heparins, Orgaran has a much higher anti-Xa/anti-IIa ratio. The inactivation of factor Xa is mediated by AT III and that of thrombin by both AT III and heparin cofactor II. Compared to heparin, which is a strong inhibitor of thrombin generation, Orgaran has only moderate inhibitory effects on thrombin generation. Orgaran shows minimal or no effects on platelet function in vitro or in vivo. It inhibits the formation of various types of thrombi (clot-like and mixed thrombi) with approximately the same potency as heparin. Both the high- and low-affinity fraction for AT III contribute to the antithrombotic activity. In contrast to heparin, Orgaran does not inhibit platelet deposition in experimental mixed thrombi unless very high doses of the heparinoid are used. Orgaran is more efficacious than heparin in preventing the extension of established venous thrombosis. Orgaran promotes less bleeding-enhancing activity than heparin in various experimental models. In addition, compared to heparin, it has only minimal effects on platelet degranulation during hemostatic plug formation.(ABSTRACT TRUNCATED AT 250 WORDS)