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.
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.
Authors: Charles L Bennett; Jonathan R Nebeker; Paul R Yarnold; Cara C Tigue; David A Dorr; June M McKoy; Beatrice J Edwards; John F Hurdle; Dennis P West; Denys T Lau; Cara Angelotta; Sigmund A Weitzman; Steven M Belknap; Benjamin Djulbegovic; Martin S Tallman; Timothy M Kuzel; Al B Benson; Andrew Evens; Steven M Trifilio; D Mark Courtney; Dennis W Raisch Journal: Arch Intern Med Date: 2007-05-28
Authors: C L Bennett; J M Connors; J M Carwile; J L Moake; W R Bell; S R Tarantolo; L J McCarthy; R Sarode; A J Hatfield; M D Feldman; C J Davidson; H M Tsai Journal: N Engl J Med Date: 2000-06-15 Impact factor: 91.245
Authors: Anaadriana Zakarija; Hau C Kwaan; Joel L Moake; Nicholas Bandarenko; Dilip K Pandey; June M McKoy; Paul R Yarnold; Dennis W Raisch; Jeffrey L Winters; Thomas J Raife; John F Cursio; Thanh Ha Luu; Elizabeth A Richey; Matthew J Fisher; Thomas L Ortel; Martin S Tallman; X Long Zheng; Masanori Matsumoto; Yoshihiro Fujimura; Charles L Bennett Journal: Kidney Int Suppl Date: 2009-02 Impact factor: 10.545
Authors: June M McKoy; Matthew J Fisher; D Mark Courtney; Dennis W Raisch; Beatrice J Edwards; Marc H Scheetz; Steven M Belknap; Steven M Trifilio; Athena T Samaras; Dustin B Liebling; Beatrice Nardone; Katrina Marie Tulas; Dennis P West Journal: Drug Saf Date: 2013-05 Impact factor: 5.606