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Clopidogrel Linked to Thrombotic Thrombocytopenic Purpura

Jane L. Miller

An article to be published in the June 15 issue of the New England Journal of Medicine describes the potential for thrombotic thrombocytopenic purpura in association with clopidogrel therapy. The editors said that they released the report early because of the potential clinical implications. As Bennett and coauthors write in the upcoming article, "The development of cardiac or neurologic changes after the initiation of clopidogrel therapy may be mistakenly attributed to the underlying condition for which it was prescribed. Physicians should be aware of the possibility of thrombotic thrombocytopenic purpura among patients who are receiving clopidogrel."

Because of its better safety profile, clopidogrel has "largely replaced" ticlopidine use in patients receiving coronary-artery stents and in patients with peripheral vascular disease or acute cardiac ischemia, noted the authors. Thrombotic thrombocytopenic purpura is estimated to occur in 1 of every 1600 to 5000 patients exposed to ticlopidine, but the link was not widely recognized until seven years after the drug was approved, wrote the authors. Clopidogrel was approved for marketing in early 1998. The authors identified reports of only two prior cases of thrombotic thrombocytopenic purpura in association with clopidogrel use, both reported at medical conferences. No cases were reported during Phase III clinical trials of the drug.

The June 15 report describes 11 cases of thrombotic thrombocytopenic purpura in patients taking clopidogrel. The cases were characterized by thrombocytopenia and microangiopathic hemolytic anemia, with or without neurologic changes or renal dysfunction. Ten of the cases were detected within the first two weeks of clopidogrel therapy. About half of the patients had received cholesterol-lowering agents. In one patient, the cholesterol-lowering agent appeared to be the cause of the syndrome. Ten patients responded to plasma exchange, but two of them required 20 or more exchanges. Two patients had several recurrences after clopidogrel was stopped. One patient died. The patients were identified by active surveillance by blood banks, hematologists, and the manufacturers.