United Kingdom. The first of a new group of anticoagulant agents is now on the market. Lepirudin (Refludan: Hoechst Marion Roussel) is a recombinant hirudin approved for use in patients with heparin-associated thrombocytopenia type II requiring parenteral antithrombotic therapy.
Hirudin - originally isolated from the leech - is a direct-acting antithrombin agent which acts independently of antithrombin III. It inhibits the thrombin catalysed activation of factors V, VIII and XIII and thrombin-induced platelet activation.
Unlike heparin, hirudin is able to inactivate fibrin-bound thrombin, thus conferring an important potential advantage over antithrombin III-dependent inhibitors (heparin and low molecular weight heparins) since fibrin-bound thrombin remains active and autocatalyses its own activity. Moreover, hirudin is not known to be associated with an immune-mediated thrombocytopenia, as can occur with heparin.
However, trials of hirudin in patients with myocardial infarction producing encouraging results were stopped due to a high rate of intracerebral bleeding. In view of the relatively low incidence of heparin- associated thrombocytopenia, use of lepirudin would not be extensive. Clinical trials to determine other uses for the product now need to be carried out. Trials in unstable angina are under way.
Reference: The Pharmaceutical Journal 260: 363, 14 March 1998.