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(Stroke. 2004;35:537.)
© 2004 American Heart Association, Inc.

Original Contributions

Editorial Comment—An Approach to the Estimation of the Risk of TTP During Clopidogrel Therapy

Saran Jonas, MD, Guest Editor Giacinto Grieco, MD, Guest Editor

Section of Quantitative Investigation, Department of Neurology, New York University School of Medicine, New York, NY

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In this issue of Stroke, Zakarija and 12 co-authors¹ describe 37 cases of thrombotic thrombocytopenic purpura (TTP) that occurred in the United States in the years 1998 to 2002 in association with clopidogrel (Plavix) therapy. This is of interest to those of us who (as characterized by Donnan and Davis²) are "strokologists," since it raises questions about our understanding of the CAPRIE study.³ In CAPRIE there were 25 cases of platelet counts <100 000 per mm³ in 9553 patients receiving clopidogrel 75 mg/d, and 25 cases in 9546 patients receiving aspirin 325 mg/d (2.6 cases per thousand with each treatment); no cases of TTP were reported.

We pose 2 questions: (1) Why did Zakarija et al find cases of TTP while the CAPRIE investigators did not? (2) Can we estimate the true risk of TTP during clopidogrel therapy?

With regard to the first question, a possible explanation is that TTP occurs late in clopidogrel treatment, and was not seen in CAPRIE because treatment duration was too short. This explanation fails for 2 reasons: (1) Zakarija et al found that TTP occurred within the first 30 days in 87.5% of cases, and (2) mean treatment duration in CAPRIE was fairly long (1.63 years). Alternatively, we could conclude that very large numbers of instances of thrombocytopenia must occur before even a single instance of TTP will develop (all 37 patients had thrombocytopenia), and that the CAPRIE cohort was too small to produce these numbers. This seems a more plausible explanation, . . . [Full Text of this Article]

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