New agents for the treatment of thrombosis

Research output: Contribution to journalArticle

Abstract

Until recently, antithrombotic drugs were limited to heparin (first used clinically in 1938), the oral anticoagulants (first used in 1939), streptokinase (shown to lyse experimental thrombi in man in 1951) and aspirin (found to inhibit platelet function and prolong the skin bleeding time in 1964). The past 10 years have brought a bewildering array of new drugs through the application of an improved understanding of haemostatic mechanisms in animals and man, and through recombinant technology. Unfractionated heparin seems about to be replaced, at least in part, by low molecular weight heparins with a longer circulating half-life and more predictable pharmacokinetics and dynamics; and there is now a completely biosynthetic pentasaccharide that incorporates the active ATIII binding site of heparin and has pure antifactor Xa activity. Clinically evaluated direct antithrombins include recombinant hirudin (first isolated as a leech salivary extract) and bio-engineered hirudin analogues. These can prevent vein thrombosis after hip surgery and also prevent re-occlusion after percutaneous transluminary coronary angioplasty (PTCA). Other new small, orally active, direct antithrombins are under evaluation. New anti-platelet drugs include Fab fragments of humanised monoclonal mouse antibodies to platelet glycoprotein IIb-IIIa, and synthetic analogues to the RGD recognition site responsible for platelet adhesion to fibrinogen and von Willebrand factor. The greatest interest in these drugs relates to their potential value for improving outcomes after PTCA or thrombolytic therapy for myocardial infarction. Concentrates of the natural anticoagulants, protein C, thrombomodulin, intrinsic pathway inhibitor, and antithrombin in have also been evaluated, both in animal models and to a lesser extent in man. In addition to their logical application for inherited deficiency states, they have a potential use in acquired deficiency, as in disseminated sepsis. Whether these new drugs will take their place in the routine management of thromboembolic disorders will depend on their efficacy and safety compared with the present generation of drugs, and on their availability and cost.

Original languageEnglish
Number of pages1
JournalAustralian Journal of Medical Science
Volume17
Issue number4
Publication statusPublished - 1996
Externally publishedYes

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