Ticlopidine- and clopidogrel-associated thrombotic thrombocytopenic purpura (TTP): Review of clinical, laboratory, epidemiological, and pharmacovigilance findings (1989-2008)

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

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a fulminant disease characterized by platelet aggregates, thrombocytopenia, renal insufficiency, neurologic changes, and mechanical injury to erythrocytes. Most idiopathic cases of TTP are characterized by a deficiency of ADAMTS13 (a disintegrin and metalloprotease, with thrombospondin-1-like domains) metalloprotease activity. Ironically, use of anti-platelet agents, the thienopyridine derivates clopidogrel and ticlopidine, is associated with drug induced TTP. Data were abstracted from a systematic review of English-language literature for thienopyridine-associated TTP identified in MEDLINE, EMBASE, the public website of the Food and Drug Administration, and abstracts from national scientific conferences from 1991 to April 2008. Ticlopidine and clopidogrel are the two most common drugs associated with TTP in FDA safety databases. Epidemiological studies identify recent initiation of anti-platelet agents as the most common risk factor associated with risks of developing TTP. Laboratory studies indicate that most cases of thienopyridine-associated TTP involve an antibody to ADAMTS13 metalloprotease, present with severe thrombocytopenia, and respond to therapeutic plasma exchange (TPE); a minority of thienopyridine-associated TTP presents with severe renal insufficiency, involves direct endothelial cell damage, and is less responsive to TPE. The evaluation of this potentially fatal drug toxicity can serve as a template for future efforts to comprehensively characterize other severe adverse drug reactions.

Original languageEnglish (US)
Pages (from-to)S20-S24
JournalKidney international
Volume75
Issue numberSUPPL. 112
DOIs
StatePublished - Feb 2009

Keywords

  • ADAMTS13
  • Drug-associated TTP
  • Epidemiology

ASJC Scopus subject areas

  • Nephrology

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    Zakarija, A., Kwaan, H. C., Moake, J. L., Bandarenko, N., Pandey, D. K., McKoy, J. M., Yarnold, P. R., Raisch, D. W., Winters, J. L., Raife, T. J., Cursio, J. F., Luu, T. H., Richey, E. A., Fisher, M. J., Ortel, T. L., Tallman, M. S., Zheng, X. L., Matsumoto, M., Fujimura, Y., & Bennett, C. L. (2009). Ticlopidine- and clopidogrel-associated thrombotic thrombocytopenic purpura (TTP): Review of clinical, laboratory, epidemiological, and pharmacovigilance findings (1989-2008). Kidney international, 75(SUPPL. 112), S20-S24. https://doi.org/10.1038/ki.2008.613