Glycosaminoglycan Related Antithrombotic Agents

Both the synthetic and natural analogues of various glycosaminoglycans have been developed for antithrombotic use. These agents are able to act through their interactions with serine protease inhibitors and by releasing TFPI from the endogeneous sites. 

Beside the above clinically used approaches, several newer dmgs to prevent thromboembolic disorders have been or are being developed. Most of these dmgs are in their early phases of development and it will take some time before their clinical efficacy is proven. 

Currently several dermatan sulfates are under development for the prophylaxis of venous thromboembolism. While similar in stmcture to heparin, these agents do not produce any effect on platelets. Furthermore, these agents ate poorly absorbed after subcutaneous administration. More recently some low molecular weight dermatans have been produced which ate absorbed subcutaneously, unlike dermatan sulfete. 

A synthetic hypersulfeted lactobionic acid amide (Aprosulate) has been developed for prophylactic antithrombotic use. This agent produces its action via heparin cofactor II and by inhibiting protease generation. The bioavailability of this agent is better than that of dermatan and heparan sulfetes. However, this product exhibits heparin-induced ftirombocytopenic effects and some teratogenetic potential. Thus, its use in clinical trials has been stopped. 

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Heparin, a sulfated glycosaminoglycan has been used clinically as an antithrombotic agent. It was discovered that a unique pentasaccharide domain in some heparin chains activates antithrombin III (AT-III), a serine protease inhibitor that blocks thrombin (factor Ila) and factor Xa in the coagulation cascade. However, heparin has some well-documented problems related to its clinical... 

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