Lepirudin

Lepirudin, a recombinant hirudin, is a direct irreversible thrombin inhibitor by binding to both free and clot-bound thrombin. It is approved for treatment of heparin-induced thrombocytopenia (HIT), which is a serious antibody-mediated drug reaction mostly associated with the use of unfractionated heparin. Clinical experience during the last 10 years has proved the efficacy of lepirudin in the management of HIT. The major route of elimination of lepirudin is the kidney, accounting for approximately 90% of its systemic clearance. The most important adverse reactions are bleeding and the induction of immunologic reactions.

Lepirudin is indicated for anticoagulation in patients with heparin-induced thrombocytopenia (HIT). We describe 2 cases of HIT and thrombosis in children with heart disease, including one that required extracorporeal membrane oxygenation. Lepirudin, dosed in the recommended adult weight--based fashion, was an effective antithrombotic agent in pediatric patients with HIT.

Deitcher, S. R., Topoulos, A. P., Bartholomew, J. R., & Kichuk-Chrisant, M. R. (2002). Lepirudin anticoagulation for heparin-induced thrombocytopenia. The Journal of pediatrics, 140(2), 264-266.

Lepirudin is one of few anticoagulants that can be safely used in patients with HIT. Because it is eliminated through the kidneys, great care must be taken when administering lepirudin to patients with renal failure; in fact, its use is currently not recommended in patients requiring hemodialysis. Lepirudin effectively prevented acute thrombosis in both of our patients with documented HIT, with no bleeding complications. We describe how we selected the initial doses and report results of aPTT monitoring.

Dager, W. E., & White, R. H. (2001). Use of lepirudin in patients with heparin-induced thrombocytopenia and renal failure requiring hemodialysis. Annals of Pharmacotherapy, 35(7-8), 885-890.

Lepirudin (Refludan), Berlex Laboratories, USA and Canada; Pharmion, all other countries), a recombinant derivative of the naturally occurring leech anticoagulant hirudin, was the first direct thrombin inhibitor to be approved by the European Agency for the Evaluation of Medicinal Products and the US Food and Drug Administration for the treatment of heparin-induced thrombocytopenia. Since its introduction into Europe and the USA, it has been studied in over 7000 patients requiring anticoagulation in conditions including acute coronary syndromes, percutaneous coronary intervention, cardiopulmonary bypass and heparin-induced thrombocytopenia. Three European clinical trials, designated Heparin-Associated Thrombocytopenia (HAT)-1, -2 and -3, demonstrated the efficacy and safety of lepirudin in the prevention and treatment of thrombosis in patients with antibody-confirmed heparin-induced thrombocytopenia.

Greinacher, A. (2004). Lepirudin: a bivalent direct thrombin inhibitor for anticoagulation therapy. Expert review of cardiovascular therapy, 2(3), 339-357.