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J Am Coll Cardiol ; 50(12): 1138-43, 2007 Sep 18.
Article in English | MEDLINE | ID: mdl-17868804

ABSTRACT

OBJECTIVES: We sought to describe clinical and laboratory findings for a large cohort of patients with thienopyridine-associated thrombotic thrombocytopenic purpura (TTP). BACKGROUND: The thienopyridine derivatives, ticlopidine and clopidogrel, are the 2 most common drugs associated with TTP in databases maintained by the U.S. Food and Drug Administration (FDA). METHODS: Clinical reports of TTP associated with clopidogrel and ticlopidine were identified from medical records, published case reports, and FDA case reports (n = 128). Duration of thienopyridine exposure, clinical and laboratory findings, and survival were recorded. ADAMTS13 activity (n = 39) and inhibitor (n = 30) were measured for a subset of individuals. RESULTS: Compared with clopidogrel-associated TTP cases (n = 35), ticlopidine-associated TTP cases (n = 93) were more likely to have received more than 2 weeks of drug (90% vs. 26%), to be severely thrombocytopenic (84% vs. 60%), and to have normal renal function (72% vs. 45%) (p < 0.01 for each). Compared with TTP patients with ADAMTS13 activity >15% (n = 13), TTP patients with severely deficient ADAMTS13 activity (n = 26) were more likely to have received ticlopidine (92.3% vs. 46.2%, p < 0.003). Among patients who developed TTP >2 weeks after thienopyridine, therapeutic plasma exchange (TPE) increased likelihood of survival (84% vs. 38%, p < 0.05). Among patients who developed TTP within 2 weeks of starting thienopyridines, survival was 77% with TPE and 78% without. CONCLUSIONS: Thrombotic thrombocytopenic purpura is a rare complication of thienopyridine treatment. This drug toxicity appears to occur by 2 different mechanistic pathways, characterized primarily by time of onset before versus after 2 weeks of thienopyridine administration. If TTP occurs after 2 weeks of ticlopidine or clopidogrel therapy, therapeutic plasma exchange must be promptly instituted to enhance likelihood of survival.


Subject(s)
Adverse Drug Reaction Reporting Systems/statistics & numerical data , Platelet Aggregation Inhibitors/adverse effects , Purpura, Thrombotic Thrombocytopenic/chemically induced , Purpura, Thrombotic Thrombocytopenic/mortality , Pyridines/adverse effects , Age Distribution , Aged , Analysis of Variance , Clopidogrel , Cohort Studies , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Plasma Exchange , Platelet Aggregation Inhibitors/therapeutic use , Probability , Purpura, Thrombotic Thrombocytopenic/therapy , Pyridines/therapeutic use , Risk Assessment , Severity of Illness Index , Sex Distribution , Survival Analysis , Ticlopidine/adverse effects , Ticlopidine/analogs & derivatives , Ticlopidine/therapeutic use
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