• A Greinacher, N Lubenow, and P Eichler.
• Institut für Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt Universität, Klinikum/Sauerbruchstrasse, 17489 Greifswald, Germany. greinach@uni-greifswald.de
• Circulation. 2003 Oct 28;108(17):2062-5.

BackgroundLepirudin (Refludan) is a hirudin derivative. It is a direct thrombin inhibitor obtained by recombinant technology from the medicinal leech and is approved for treatment of heparin-induced thrombocytopenia complicated by thrombosis. Because 3 cases of fatal anaphylaxis possibly associated with use of lepirudin have been reported, we initiated an investigation of putative lepirudin-associated anaphylaxis.Methods And ResultsAided by the manufacturer (Schering AG, Berlin, Germany), we used the lepirudin study databases to identify all patients in whom possible anaphylaxis/severe allergy was recorded from 1994 to September 2002. The 26 possible cases identified were reviewed independently by 2 investigators. After excluding patients with mild skin reactions, reactions likely caused by concomitant medications, poorly documented cases, and reactions that did not correspond temporally with lepirudin use, there remained 9 patients judged to have had severe anaphylaxis in close temporal association with lepirudin. All reactions occurred within minutes of intravenous lepirudin administration, with 4 fatal outcomes (3 acute cardiorespiratory arrests, 1 hypotension-induced myocardial infarction). In these 4 cases, a previous uneventful treatment course with lepirudin was identified (1 to 12 weeks earlier). We recorded high-titer IgG-anti-lepirudin antibodies in an additional patient with anaphylaxis. Because lepirudin has been used in approximately 35 000 patients, the risk of anaphylaxis is approximately 0.015% (5 of 32 500) on first exposure and 0.16% (4 of 2500) in reexposed patients (7.5% estimated reexposures).ConclusionsLepirudin can cause fatal anaphylaxis, particularly in patients who are treated within 3 months of a previous exposure. The overall risk/benefit assessment of lepirudin as a treatment for heparin-induced thrombocytopenia remains favorable.

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