Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura

A 20-year review from the southern network on adverse reactions (SONAR)

Sony Jacob, Brianne L. Dunn, Zaina P. Qureshi, Nicholas Bandarenko, Hau C. Kwaan, Dilip K. Pandey, June M McKoy, Sara E. Barnato, Jeffrey L. Winters, John F. Cursio, Ivy Weiss, Thomas J. Raife, Patricia M. Carey, Ravindra Sarode, Joseph E. Kiss, Constance Danielson, Thomas L. Ortel, William F. Clark, Gail Rock, Masanori Matsumoto & 7 others Yoshihiro Fujimura, X. Long Zheng, Hao Chen, Fei Chen, John M. Armstrong, Dennis W. Raisch, Charles L. Bennett*

*Corresponding author for this work

Research output: Contribution to journalReview article

41 Citations (Scopus)

Abstract

Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p<0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ.

Original languageEnglish (US)
Pages (from-to)845-853
Number of pages9
JournalSeminars in Thrombosis and Hemostasis
Volume38
Issue number8
DOIs
StatePublished - Oct 31 2012

Fingerprint

clopidogrel
Ticlopidine
Thrombotic Thrombocytopenic Purpura
Thienopyridines
Thrombospondin 1
Disintegrins
Prasugrel Hydrochloride
Platelet Aggregation Inhibitors
Metalloproteases
Marketing
Pharmaceutical Preparations

Keywords

  • adverse event
  • clopidogrel
  • prasugrel
  • thrombotic thrombocytopenic purpura
  • ticlopidine

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine

Cite this

Jacob, Sony ; Dunn, Brianne L. ; Qureshi, Zaina P. ; Bandarenko, Nicholas ; Kwaan, Hau C. ; Pandey, Dilip K. ; McKoy, June M ; Barnato, Sara E. ; Winters, Jeffrey L. ; Cursio, John F. ; Weiss, Ivy ; Raife, Thomas J. ; Carey, Patricia M. ; Sarode, Ravindra ; Kiss, Joseph E. ; Danielson, Constance ; Ortel, Thomas L. ; Clark, William F. ; Rock, Gail ; Matsumoto, Masanori ; Fujimura, Yoshihiro ; Zheng, X. Long ; Chen, Hao ; Chen, Fei ; Armstrong, John M. ; Raisch, Dennis W. ; Bennett, Charles L. / Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura : A 20-year review from the southern network on adverse reactions (SONAR). In: Seminars in Thrombosis and Hemostasis. 2012 ; Vol. 38, No. 8. pp. 845-853.
@article{b23cc56afe1742db85d2204ecfbce00c,
title = "Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura: A 20-year review from the southern network on adverse reactions (SONAR)",
abstract = "Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80{\%} and antibodies to 100{\%} of these TTP patients on ticlopidine, 0{\%} of the patients with clopidogrel-associated TTP (p<0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ.",
keywords = "adverse event, clopidogrel, prasugrel, thrombotic thrombocytopenic purpura, ticlopidine",
author = "Sony Jacob and Dunn, {Brianne L.} and Qureshi, {Zaina P.} and Nicholas Bandarenko and Kwaan, {Hau C.} and Pandey, {Dilip K.} and McKoy, {June M} and Barnato, {Sara E.} and Winters, {Jeffrey L.} and Cursio, {John F.} and Ivy Weiss and Raife, {Thomas J.} and Carey, {Patricia M.} and Ravindra Sarode and Kiss, {Joseph E.} and Constance Danielson and Ortel, {Thomas L.} and Clark, {William F.} and Gail Rock and Masanori Matsumoto and Yoshihiro Fujimura and Zheng, {X. Long} and Hao Chen and Fei Chen and Armstrong, {John M.} and Raisch, {Dennis W.} and Bennett, {Charles L.}",
year = "2012",
month = "10",
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language = "English (US)",
volume = "38",
pages = "845--853",
journal = "Seminars in Thrombosis and Hemostasis",
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Jacob, S, Dunn, BL, Qureshi, ZP, Bandarenko, N, Kwaan, HC, Pandey, DK, McKoy, JM, Barnato, SE, Winters, JL, Cursio, JF, Weiss, I, Raife, TJ, Carey, PM, Sarode, R, Kiss, JE, Danielson, C, Ortel, TL, Clark, WF, Rock, G, Matsumoto, M, Fujimura, Y, Zheng, XL, Chen, H, Chen, F, Armstrong, JM, Raisch, DW & Bennett, CL 2012, 'Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura: A 20-year review from the southern network on adverse reactions (SONAR)', Seminars in Thrombosis and Hemostasis, vol. 38, no. 8, pp. 845-853. https://doi.org/10.1055/s-0032-1328894

Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura : A 20-year review from the southern network on adverse reactions (SONAR). / Jacob, Sony; Dunn, Brianne L.; Qureshi, Zaina P.; Bandarenko, Nicholas; Kwaan, Hau C.; Pandey, Dilip K.; McKoy, June M; Barnato, Sara E.; Winters, Jeffrey L.; Cursio, John F.; Weiss, Ivy; Raife, Thomas J.; Carey, Patricia M.; Sarode, Ravindra; Kiss, Joseph E.; Danielson, Constance; Ortel, Thomas L.; Clark, William F.; Rock, Gail; Matsumoto, Masanori; Fujimura, Yoshihiro; Zheng, X. Long; Chen, Hao; Chen, Fei; Armstrong, John M.; Raisch, Dennis W.; Bennett, Charles L.

In: Seminars in Thrombosis and Hemostasis, Vol. 38, No. 8, 31.10.2012, p. 845-853.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura

T2 - A 20-year review from the southern network on adverse reactions (SONAR)

AU - Jacob, Sony

AU - Dunn, Brianne L.

AU - Qureshi, Zaina P.

AU - Bandarenko, Nicholas

AU - Kwaan, Hau C.

AU - Pandey, Dilip K.

AU - McKoy, June M

AU - Barnato, Sara E.

AU - Winters, Jeffrey L.

AU - Cursio, John F.

AU - Weiss, Ivy

AU - Raife, Thomas J.

AU - Carey, Patricia M.

AU - Sarode, Ravindra

AU - Kiss, Joseph E.

AU - Danielson, Constance

AU - Ortel, Thomas L.

AU - Clark, William F.

AU - Rock, Gail

AU - Matsumoto, Masanori

AU - Fujimura, Yoshihiro

AU - Zheng, X. Long

AU - Chen, Hao

AU - Chen, Fei

AU - Armstrong, John M.

AU - Raisch, Dennis W.

AU - Bennett, Charles L.

PY - 2012/10/31

Y1 - 2012/10/31

N2 - Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p<0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ.

AB - Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p<0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ.

KW - adverse event

KW - clopidogrel

KW - prasugrel

KW - thrombotic thrombocytopenic purpura

KW - ticlopidine

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U2 - 10.1055/s-0032-1328894

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VL - 38

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JO - Seminars in Thrombosis and Hemostasis

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