Thrombotic thrombocytopenic purpura associated with clopidogrel.

Background: The antiplatelet drug clopidogrel is a new thienopyridine deriv ative whose mechanism of action and chemical structure are similar to those of ticlopidine. The estimated incidence of ticlopidine-associated thrombot ic thrombocytopenic purpura is 1 per 1600 to 5000 patients treated, whereas no clopidogrel-associated cases were observed among 20,000 closely monitor ed patients treated in phase 3 clinical trials and cohort studies. Because of the association between ticlopidine use and thrombotic thrombocytopenic purpura and other adverse effects, clopidogrel has largely replaced ticlopi dine in clinical practice. More than 3 million patients have received clopi dogrel. We report the clinical and laboratory findings in 11 patients in wh om thrombotic thrombocytopenic purpura developed during or soon after treat ment with clopidogrel. Methods: The 11 patients were identified by active surveillance by the medi cal directors of blood banks (3 patients), hematologists (6), and the manuf acturers of clopidogrel (2). Results: Ten of the 11 patients received clopidogrel for 14 days or less be fore the onset of thrombotic thrombocytopenic purpura. Although 10 of the 1 1 patients had a response to plasma exchange, 2 required 20 or more exchang es before clinical improvement occurred, and 2 had relapses while not recei ving clopidogrel. One patient died despite undergoing plasma exchange soon after diagnosis. Conclusions: Thrombotic thrombocytopenic purpura can occur after the initia tion of clopidogrel therapy, often within the first two weeks of treatment. Physicians should be aware of the possibility of this syndrome when initia ting clopidogrel treatment. (N Engl J Med 2000;342:1773-7.) (C)2000, Massac husetts Medical Society.