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(Stroke. 2004;35:533.)
© 2004 American Heart Association, Inc.

Original Contributions

Clopidogrel-Associated TTP

An Update of Pharmacovigilance Efforts Conducted by Independent Researchers, Pharmaceutical Suppliers, and the Food and Drug Administration

Anaadriana Zakarija, MD; Nicholas Bandarenko, MD; Dilip K. Pandey, MBBS, MS, PhD; Amy Auerbach, BA; Dennis W. Raisch, PhD; Benjamin Kim, MD; Hau C. Kwaan, MD, PhD; June M. McKoy, MPH, MD, JD; Brian P. Schmitt, MPH, MD; Charles J. Davidson, MD; Paul R. Yarnold, PhD; Philip B. Gorelick, MD Charles L. Bennett, MPP, MD, PhD

From the VA Chicago Healthcare System, VA Midwest Center for Health Services and Policy Research, Division of Hematology/Oncology, Department of Medicine, Center for Healthcare Studies, and the Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical Center, Chicago Ill (A.Z., A.A., B.K., H.C.K., J.M.M., B.P.S., C.J.D., P.R.Y., C.L.B.); University of North Carolina, Chapel Hill (N.B.); VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, University of New Mexico, Albuquerque (D.W.R.); and Department of Neurologic Sciences, RUSH Presbyterian-St Luke’s Medical Center, Chicago, Ill (D.K.P., P.B.G.).

Reprint requests to Charles L. Bennett, Division of Hematology/Oncology, Department of Medicine, 400 E Ontario St, Suite 205, Chicago IL 60611. E-mail cbenne{at}northwestern.edu

Background and Purpose— Since the 1999 identification of clopidogrel-associated thrombotic thrombocytopenic purpura (TTP) through independent active surveillance, subsequent cases have been identified by pharmaceutical suppliers of clopidogrel and the Food and Drug Administration (FDA). For cases of clopidogrel-associated TTP reported between 1998 to 2002, we evaluated the quality and timeliness of data from 3 reporting systems-independent active surveillance (n=13), pharmaceutical suppliers (n=24), and the FDA (n=13)—and identified prognostic factors associated with mortality.

Methods— This study assessed the completeness of information on TTP diagnosis, treatment response, and causality from the 3 reporting systems. In addition, predictors of mortality were identified through classification tree analysis.

Results— Completeness, timeliness, and certainty of diagnosis were best for cases obtained by active surveillance, intermediate for cases reported to the pharmaceutical supplier, and poorest for cases reported directly to the FDA. Clopidogrel had been used for 2 weeks by 65%. The survival rate for patients with clopidogrel-associated TTP was 71.2%. Receipt of therapeutic plasma exchange within 3 days of onset of TTP increased the likelihood of survival (100% versus 27.3%, P<0.001).

Conclusions— Compared with reports submitted by suppliers or the FDA, reports obtained through active surveillance provided timelier and more complete information. Clopidogrel-associated TTP often occurs within 2 weeks of drug initiation, occasionally relapses, and has a high mortality if not treated promptly.

Key Words: adverse drug reaction reporting systems • antiplatelet agents • purpura, thrombotic thrombocytopenic

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