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Thrombotic Thrombocytopenic Purpura and Clopidogrel

Clopidogrel, a derivative of thienopyridine with antiplatelet properties, may be associated with the development of thrombotic thrombocytopenic purpura (TTP). Its mechanism of action and chemical structure are similar to those of ticlopidine, another antiplatelet drug that has been linked with TTP (estimated incidence, 1 case per 1600 to 5000 patients treated). Since its approval by the FDA in 1997, clopidogrel has been given to more than 3 million people. This article describes 11 patients who developed TTP during or soon after treatment with clopidogrel.

Patients were identified by the medical directors of blood banks (3 patients), by hematologists (6), and through a surveillance program overseen by the 2 manufacturers of clopidogrel (2). Ten of the 11 patients had been using clopidogrel for less than 2 weeks before onset of TTP. In all patients, the disease was manifested by thrombocytopenia and microangiopathic hemolytic anemia, with or without neurologic changes or renal dysfunction. All patients underwent plasma exchange; symptoms resolved in 10 of the 11 after a median of 8 exchanges. One patient died.

Comment: This case report suggests that clopidogrel may be associated with thrombotic thrombocytopenic purpura. The incidence appears low, for there were no clopidogrel-associated TTP cases observed among the 20,000 closely monitored patients who were treated in phase 3 clinical trials and cohort studies. Nevertheless, physicians should be alert to the possibility of TTP development among patients who receive clopidogrel, particularly soon after initiation of therapy.

— HM Krumholz

Published in Journal Watch Cardiology January 1, 2001

Citation(s):

Bennett CL et al. Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med 2000 Jun 15 342 1773-1777.

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