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.
authors.affiliation: South Carolina Center of Economic Excellence for Medication Safety and Efficacy, South Carolina College of Pharmacy, USA.
authors.forename: Sony
authors.initials: S
authors.lastname: Jacob
authors.forename: Brianne L
authors.initials: BL
authors.lastname: Dunn
authors.forename: Zaina P
authors.initials: ZP
authors.lastname: Qureshi
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bandarenko
authors.forename: Hau C
authors.initials: HC
authors.lastname: Kwaan
authors.forename: Dilip K
authors.initials: DK
authors.lastname: Pandey
authors.forename: June M
authors.initials: JM
authors.lastname: McKoy
authors.forename: Sara E
authors.initials: SE
authors.lastname: Barnato
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Winters
authors.forename: John F
authors.initials: JF
authors.lastname: Cursio
authors.forename: Ivy
authors.initials: I
authors.lastname: Weiss
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Raife
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Carey
authors.forename: Ravindra
authors.initials: R
authors.lastname: Sarode
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Kiss
authors.forename: Constance
authors.initials: C
authors.lastname: Danielson
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Ortel
authors.forename: William F
authors.initials: WF
authors.lastname: Clark
authors.forename: Gail
authors.initials: G
authors.lastname: Rock
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimura
authors.forename: X Long
authors.initials: XL
authors.lastname: Zheng
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: John M
authors.initials: JM
authors.lastname: Armstrong
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Raisch
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bennett
mesh_terms: D000077144:Clopidogrel; D006801:Humans; D010879:Piperazines / Q000009:adverse effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D000068799:Prasugrel Hydrochloride; D011697:Purpura, Thrombotic Thrombocytopenic / Q000139:chemically induced*; D058924:Thienopyridines / Q000009:adverse effects*; D013876:Thiophenes / Q000009:adverse effects; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058924:Thienopyridines; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine