Plavix (clopidogrel) and TTP
Volume X, Issue 5
Harold J. DeMonaco, M.S. Director of Drug Therapy Management

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With permission from: http://medstat.med.utah.edu/WebPath/HEMEHTML/HEME010.html

The New England Journal of Medicine recently released the results of a study to be published in June concerning Plavix (clopidogrel) and thrombotic thrombocytopenic purpura (TPP) http://www.nejm.org/content/bennett/1.asp . In the report, Bennett and colleagues report on their evaluation of eleven case reports of TTP associated with the use of Plavix. Ticlid (ticlopidine), the clinical precursor to Plavix, has an associated incidence of TTP of 1:1600 to 1:5000, cases according to the Bennett report. Until this early release, TTP was not associated with the use of Plavix. There were no reports of TTP in nearly 20,000 patients entered into Phase III clinical trials with Plavix. Bennett and colleagues conducted an active surveillance program that included contacting blood banks, hematologists and the manufacturers/distributors of Plavix (Sanofi-Synthelabo and Bristol-Myers Squibb). Bennett allegedly undertook the review after a family friend developed TTP coincident with the use of Plavix (http://abcnews.go.com/sections/living/DailyNews/heartdrug000420.html).


Here’s the demographics of the 11 cases identified by Bennett:

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The majority of the patients who developed TTP did so within 14 days of therapy with Plavix. Five of the eleven cases were treated concomitantly with cholesterol-lowering drugs. In addition to thrombocytopenia and microangiographic hemolytic anemia, 7 of the 11 cases developed neurologic symptoms including disorientation, slurred speech, confusion, aphasia and coma.

The relationship between the concomitant administration of HMG-CoA reductase inhibitors and the development of TTP is unclear. All patients underwent plasma exchange. Ten of the eleven patients had symptoms resolve after a median of 8 plasma exchanges (range 1-30). Importantly, unlike cases of TTP with Ticlid, recurrences after plasma exchange occurred frequently. Recurrence of TTP is possible, with one case occurring 7 months after drug discontinuation. One patient died after 4 days of plasma exchange.

Implications for clinicians:

  • Although infrequent (11 cases in 2 million patients), TTP is associated with the use of Plavix usually within the first 2 weeks of therapy.
  • Concomitant administration of a HMG CoA reductase inhibitor may play a role in the development of TTP
  • Early plasma exchange appears to be an effective treatment modality. Patients underwent a median of 8 plasma exchanges (range 1-30). Recurrences of TTP occurred in several patients.
  • Patients should be advised of the potential for TTP and provided information about early warning signs.