Anaphylactic and Anaphylactoid Reactions Associated With Lepirudin in Patients With Heparin-Induced Thrombocytopenia

Abstract

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.

CD4+ T Cell-Specific Deletion of IL-4 Receptor α Prevents Ovalbumin-Induced Anaphylaxis by an IFN-γ-Dependent Mechanism

“…IgG-mediated anaphylactic reactions have been reported in humans (10,12,28), but the mechanisms of IgG-dependent anaphylaxis are uncertain. In vitro, Ag-specific IgG can cause human basophil/mast degranulation and release of mediators (29,30).…”

Heparin-Induced Thrombocytopenia

“…Fatal anaphylaxis after intravenous bolus administration has been reported in patients who received lepirudin within the previous few months. 15 …”

Les différentes alternatives d’anticoagulation au couple héparine/protamine en chirurgie cardiaque sous circulation extra-corporelle

“…Le risque anaphylactique peut être gravissime avec plusieurs cas de choc anaphylactique fatal, particulièrement en cas de réexposition. 16 Une surveillance rapprochée est de ce fait nécessaire.…”