text: Lepirudin is approved for the treatment of heparin-induced thrombocytopenia (HIT) in the USA, Canada, Europe and Australia. HIT is a very serious adverse event related to heparin and occurs with both unfractionated heparin and LMWH, although to a lesser extent with the latter. It is an immune-mediated, prothrombotic complication which results from a platelet-activating immune response triggered by the interaction of heparin with platelet factor 4 (PF4). The PF4-heparin complex can activate platelets and may cause venous and arterial thrombosis. When lepirudin binds to thrombin it hinders its prothrombic activity. Three prospective studies, called the Heparin-Associated-Thrombocytopenia (HAT) 1,2, and 3, were performed that compared lepirudin with historical controls in the treatment of HIT. All three studies showed that the risk of new thrombosis was decreased with the use of lepirudin, but the risk for major bleeding was increased. The higher incidence of major bleeding is thought to be the result of an approved dosing regimen that was too high, consequently the recommended dose was halved from the initial dose.
  As of May 2012 Bayer HealthCare, the only manufacturer of lepirudin injections, discontinued its production. They expect supplies from wholesalers to be depleted by mid-2013.