Two mechanistic pathways for thienopyridine-associated thrombotic thrombocytopenic purpura: a report from the SERF-TTP Research Group and the RADAR Project.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Bennett, CL; Kim, B; Zakarija, A; Bandarenko, N; Pandey, DK; Buffie, CG; McKoy, JM; Tevar, AD; Cursio, JF; Yarnold, PR; Kwaan, HC; De Masi, D; Sarode, R; Raife, TJ; Kiss, JE; Raisch, DW; Davidson, C; Sadler, JE; Ortel, TL; Zheng, XL; Kato, S; Matsumoto, M; Uemura, M; Fujimura, Y; SERF-TTP Research Group,

Published Date

  • September 18, 2007

Published In

Volume / Issue

  • 50 / 12

Start / End Page

  • 1138 - 1143

PubMed ID

  • 17868804

Pubmed Central ID

  • 17868804

Electronic International Standard Serial Number (EISSN)

  • 1558-3597

Digital Object Identifier (DOI)

  • 10.1016/j.jacc.2007.04.093

Language

  • eng

Conference Location

  • United States