Thrombotic thrombocytopenic purpura associated with ticlopidine in the setting of coronary artery stents and stroke prevention

Background: One of the most unusual causes of thrombotic thrombocytopenic p urpura (TTP), a life-threatening disease, is ticlopidine hydrochloride, an antiplatelet agent used to prevent strokes in high-risk populations or foll owing coronary artery stent placement. Recently, Hoffman-LaRoche Pharmaceut icals, following reports of 20 deaths from ticlopidine-associated TTP, upda ted the information about the hematologic adverse effects of the drug. Objectives: To review our recent findings on ticlopidine-associated hematol ogic toxic effects, which sewed as the impetus for the revised warnings, an d to discuss the implications of these findings. Methods: Data were obtained from the Food and Drug Administration's MedWatc h program, published phase 3 clinical trials and case reports, hematologist s, and plasmapheresis centers. Results: No cases of TTP have been reported in phase 3 ticlopidine trials. In contrast, postmarketing surveillance has identified serious adverse drug reactions to ticlopidine, resulting in 259 deaths, with TTP accounting for 40 of these deaths. Detailed information was available on 98 cases of ticl opidine-associated TTP. Compared with 42 patients in the coronary artery st ent setting, 56 patients with ticlopidine-associated TTP in the stroke prev ention setting were more likely to be women (62.5% vs 28.6%; P =.01). Befor e the onset of TTP in patients receiving stroke prevention therapy and pati ents with stent placement, ticlopidine had been used for less than 2 weeks in 5.4% and 2.4%, between 2 and 3 weeks in 17.9% and 21.4%, between 3 and 4 weeks in 30.4% and 38.1%, and between 4 and 12 weeks in 46.4% and 38.1%, r espectively. Death occurred in almost 60% of all patients not receiving pla smapheresis compared with 21.9% of patients receiving plasmapheresis for st roke prevention and 14.3% of patients receiving plasmapheresis in the stent setting. Conclusions: Use of ticlopidine requires frequent physician visits and labo ratory tests for at least 3 months in the stroke prevention setting, while, with short-term use in the coronary artery stent setting, adverse events a re less likely to occur. These factors, as well as competition from clopido grel bisulfate, a new antiplatelet agent, potentially limit the feasibility of ticlopidine as a stroke prevention agent, while having less impact on i ts use following coronary artery stent placement.