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Steven R. Steinhubl, MD; Walter A. Tan, MD; JoAnne M. Foody, MD; Eric J. Topol, MD; for the EPISTENT Investigators

JAMA. 1999;281:806-810.

Context  Thrombotic thrombocytopenic purpura (TTP) is a rare and often fatal disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, mental status changes, and renal dysfunction. Ticlopidine hydrochloride is 1 of several drugs that have been associated with this disorder and is currently used routinely in the approximately 500,000 patients per year in the United States who undergo a percutaneous coronary intervention involving a stent.

Objectives  To determine the incidence and describe the clinical course of TTP due to ticlopidine therapy following stenting.

Design  Retrospective analysis of cohort of all patients undergoing coronary stenting at the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) study sites.

Setting  Sixty-three centers throughout the United States and Canada.

Patients  A total of 43,322 patients who underwent a percutaneous coronary intervention and received a coronary stent during a 1-year period from 1996 to 1997.

Main Outcome Measures  Cases of TTP following stenting during the 1-year period to determine the incidence of TTP due to ticlopidine therapy following coronary stenting. Additional cases were collected from these and other centers across North America to further describe the clinical presentation and course of TTP due to ticlopidine therapy following stenting.

Results  Nine cases of TTP following stenting were recognized at the 63 centers during the specified period, giving an incidence of 1 case per 4814 patients treated (0.02%; 95% confidence interval, 1 case per 2533 to 1 case per 10,541 patients treated). Ten additional cases of TTP related to ticlopidine therapy following stenting were identified from other centers, were identified from the primary centers outside the predefined period, or involved a noncoronary stent. Four patients (21%) received ticlopidine for 2 weeks or fewer, 14 patients (74%) for 2 to 4 weeks, and 1 patient (5%) for 8 weeks. The mean time of ticlopidine treatment prior to TTP diagnosis was 22 days (range, 5-60 days). The overall mortality rate was 21% (4/19), with all 4 deaths occurring in patients not treated with plasmapheresis, whereas there were no deaths among the 13 patients who received plasmapheresis.

Conclusion  The findings of a TTP incidence of 0.02% in our cohort of ticlopidine-treated patients following coronary stenting suggests that TTP occurs much more commonly in this population than the estimated incidence of 0.0004% in the general population. The mortality rate for this rare complication exceeds 20%. Limiting ticlopidine therapy to 2 weeks after stenting does not prevent the development of TTP. Rapid diagnosis and treatment that includes plasmapheresis are critical for improved survival.

Author Affiliations: Department of Cardiology, Wilford Hall Medical Center, Lackland Air Force Base, San Antonio, Tex (Dr Steinhubl); and the Department of Cardiology and the Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic Foundation, Cleveland, Ohio (Drs Tan, Foody, and Topol).

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RELATED LETTER

Ticlopidine and TTP After Coronary Stenting
Charles L. Bennett, Charles J. Davidson, David Green, Peter D. Weinberg, Marc D. Feldman, Peter A. McCullough, Keisha R. Marks, Steven R. Steinhubl, Walter A. Tan, JoAnne M. Foody, and Eric J. Topol
JAMA. 1999;282(18):1717-1719.
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