Thrombotic Thrombocytopenic Purpura Associated with Clopidogrel
Charles L. Bennett, M.D., Ph.D., Jean M. Connors, M.D., John M. Carwile, M.D., Joel L. Moake, M.D., William R. Bell, M.D., Ph.D., Stefano R. Tarantolo, M.D., Leo J. McCarthy, M.D., Ravindra Sarode, M.D., Amy J. Hatfield, Pharm.D., Marc D. Feldman, M.D., Charles J. Davidson, M.D., and Han-Mou Tsai, M.D.
Background The antiplatelet drug clopidogrel is a new thienopyridinederivative whose mechanism of action and chemical structureare similar to those of ticlopidine. The estimated incidenceof ticlopidine-associated thrombotic thrombocytopenic purpurais 1 per 1600 to 5000 patients treated, whereas no clopidogrel-associatedcases were observed among 20,000 closely monitored patientstreated in phase 3 clinical trials and cohort studies. Becauseof the association between ticlopidine use and thrombotic thrombocytopenicpurpura and other adverse effects, clopidogrel has largely replacedticlopidine in clinical practice. More than 3 million patientshave received clopidogrel. We report the clinical and laboratoryfindings in 11 patients in whom thrombotic thrombocytopenicpurpura developed during or soon after treatment with clopidogrel.
Methods The 11 patients were identified by active surveillanceby the medical directors of blood banks (3 patients), hematologists(6), and the manufacturers of clopidogrel (2).
Results Ten of the 11 patients received clopidogrel for 14 daysor less before the onset of thrombotic thrombocytopenic purpura.Although 10 of the 11 patients had a response to plasma exchange,2 required 20 or more exchanges before clinical improvementoccurred, and 2 had relapses while not receiving clopidogrel.One patient died despite undergoing plasma exchange soon afterdiagnosis.
Conclusions Thrombotic thrombocytopenic purpura can occur afterthe initiation of clopidogrel therapy, often within the firsttwo weeks of treatment. Physicians should be aware of the possibilityof this syndrome when initiating clopidogrel treatment.
Source Information
From the Veterans Affairs Chicago Healthcare System, Lakeside Division (C.L.B.), and the Divisions of Hematology–Oncology (C.L.B.) and Cardiology (C.J.D.), Department of Medicine, the Robert H. Lurie Comprehensive Cancer Center (C.L.B.), and the Institute for Health Services Research and Policy Studies (C.L.B.), Northwestern University — both in Chicago; the Hematology Division, Department of Medicine, Harvard Medical School, and Clinical Laboratories, Department of Pathology, Brigham and Women's Hospital — both in Boston (J.M. Connors); the Division of Hematology–Oncology, Department of Medicine, Baylor College of Medicine, Houston (J.M. Carwile, J.L.M.); the Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore (W.R.B.); the Division of Hematology–Oncology, Department of Medicine, University of Nebraska Medical Center at Omaha, Omaha (S.R.T.); the Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis (L.J.M.); the Department of Pathology, University Hospitals of Cleveland, and Case Western Reserve University, Cleveland (R.S.); the Mission St. Joseph's Health System, Asheville, N.C., and the University of North Carolina–Chapel Hill School of Pharmacy, Chapel Hill (A.J.H.); the Division of Cardiology, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio (M.D.F.); and the Division of Hematology, Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, N.Y. (H.-M.T.). Another author was Elizabeth L. Michalets, Pharm.D. (University of North Carolina–Chapel Hill School of Pharmacy, Chapel Hill).
Address reprint requests to Dr. Bennett at the VA Chicago Healthcare System, Lakeside Division, Chicago, IL 60611, or at cbenne{at}nwu.edu.
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