Published online before print October 20, 2003, doi: 10.1161/01.CIR.0000096056.37269.14
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(Circulation. 2003;108:2062.)
© 2003 American Heart Association, Inc.
Brief Rapid Communications |
Anaphylactic and Anaphylactoid Reactions Associated With Lepirudin in Patients With Heparin-Induced Thrombocytopenia
From the Institut für Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt-Universität Greifswald, Germany.
Correspondence to Prof Dr med A. Greinacher, Ernst-Moritz-Arndt Universität, Institut für Immunologie und Transfusionsmedizin, Klinikum/Sauerbruchstrasse, 17489 Greifswald, Germany. E-mail greinach{at}uni-greifswald.de
Received February 3, 2003; de novo received July 18, 2003; revision received September 2, 2003; accepted September 4, 2003.
Background— Lepirudin (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 Results— Aided 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 
35 000 patients, the risk of anaphylaxis is 0.015% (5 of 32 500) on first exposure and 0.16% (4 of 2500) in reexposed patients (7.5% estimated reexposures).
Conclusion— Lepirudin 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.
Key Words: hirudin • antibodies • anticoagulants • shock, anaphylactic
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