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; Yoshihiro Fujimura; X. Long Zheng; Hao Chen; Fei Chen; John M. Armstrong; Dennis W. Raisch; Charles L. Bennett

doi:10.1055/s-0032-1328894

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2012; 38(08): 845-853
DOI: 10.1055/s-0032-1328894

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Ticlopidine-, Clopidogrel-, and Prasugrel-Associated Thrombotic Thrombocytopenic Purpura: A 20-Year Review from the Southern Network on Adverse Reactions (SONAR)

Sony Jacob

¹South Carolina Center of Economic Excellence for Medication Safety and Efficacy and the Southern Network on Adverse Reactions (SONAR), South Carolina College of Pharmacy, South Carolina

²WJB Dorn VA Medical Center, Columbia, South Carolina

,

Brianne L. Dunn

¹South Carolina Center of Economic Excellence for Medication Safety and Efficacy and the Southern Network on Adverse Reactions (SONAR), South Carolina College of Pharmacy, South Carolina

²WJB Dorn VA Medical Center, Columbia, South Carolina

,

Zaina P. Qureshi

¹South Carolina Center of Economic Excellence for Medication Safety and Efficacy and the Southern Network on Adverse Reactions (SONAR), South Carolina College of Pharmacy, South Carolina

,

Nicholas Bandarenko

³Duke University Medical Center, Durham, North Carolina

,

Hau C. Kwaan

⁴Northwestern University Feinberg School of Medicine, Chicago, Illinois

,

Dilip K. Pandey

⁵University of Illinois Medical Center at Chicago, Chicago, Illinois

,

June M. McKoy

⁴Northwestern University Feinberg School of Medicine, Chicago, Illinois

,

Sara E. Barnato

⁴Northwestern University Feinberg School of Medicine, Chicago, Illinois

,

Jeffrey L. Winters

⁶Mayo Clinic, Rochester Minnesota

,

John F. Cursio

⁷Rush University Medical Center, Chicago, Illinois

,

Ivy Weiss

⁴Northwestern University Feinberg School of Medicine, Chicago, Illinois

,

Thomas J. Raife

⁸University of Iowa, Iowa City, Iowa

,

Patricia M. Carey

⁹Hoxworth Blood Center, University of Cincinnati, Cincinnati, Ohio

,

Ravindra Sarode

¹⁰University of Texas Southwestern, Dallas, Texas

,

Joseph E. Kiss

¹¹The Institute for Transfusion Medicine and the University of Pittsburgh, Pittsburgh, Pennsylvania

,

Constance Danielson

¹²Indiana University School of Medicine, Indianapolis, Indiana

,

Thomas L. Ortel

³Duke University Medical Center, Durham, North Carolina

,

William F. Clark

¹³London Health Sciences Centre, London, Ontario, Canada

,

Gail Rock

¹⁴Canadian Apheresis Group, Ottawa, Ontario, Canada

,

Masanori Matsumoto

¹⁵Department of Blood Transfusion Medicine, Nara Medical University, Nara, Japan

,

Yoshihiro Fujimura

¹⁵Department of Blood Transfusion Medicine, Nara Medical University, Nara, Japan

,

X. Long Zheng

¹⁶Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

,

Hao Chen

¹⁷eHealthMe, Madison, Wisconsin

,

Fei Chen

¹⁷eHealthMe, Madison, Wisconsin

,

John M. Armstrong

¹⁸Lead Horse Technologies, Junction City, Kansas

,

Dennis W. Raisch

¹⁹College of Pharmacy, University of New Mexico, Albuquerque, New Mexico

,

Charles L. Bennett

¹South Carolina Center of Economic Excellence for Medication Safety and Efficacy and the Southern Network on Adverse Reactions (SONAR), South Carolina College of Pharmacy, South Carolina

²WJB Dorn VA Medical Center, Columbia, South Carolina

²⁰Arnold School of Public Health of the University of South Carolina, Columbia, South Carolina

²¹Hollings Cancer Center of the Medical University of South Carolina, Charleston, South Carolina

› Author Affiliations

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

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

Full Text

References

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