Clopidogrel-associated TTP: an update of pharmacovigilance efforts conducted by independent researchers, pharmaceutical suppliers, and the Food and Drug Administration.
OBJECTIVE
Since the 1999 identification of clopidogrel-associated thrombotic thrombocytopenic purpura (TTP) through independent active surveillance, subsequent cases have been identified by pharmaceutical suppliers of clopidogrel and the Food and Drug Administration (FDA). For cases of clopidogrel-associated TTP reported between 1998 to 2002, we evaluated the quality and timeliness of data from 3 reporting systems-independent active surveillance (n=13), pharmaceutical suppliers (n=24), and the FDA (n=13)-and identified prognostic factors associated with mortality.


METHODS
This study assessed the completeness of information on TTP diagnosis, treatment response, and causality from the 3 reporting systems. In addition, predictors of mortality were identified through classification tree analysis.


RESULTS
Completeness, timeliness, and certainty of diagnosis were best for cases obtained by active surveillance, intermediate for cases reported to the pharmaceutical supplier, and poorest for cases reported directly to the FDA. Clopidogrel had been used for </=2 weeks by 65%. The survival rate for patients with clopidogrel-associated TTP was 71.2%. Receipt of therapeutic plasma exchange within 3 days of onset of TTP increased the likelihood of survival (100% versus 27.3%, P<0.001).


CONCLUSIONS
Compared with reports submitted by suppliers or the FDA, reports obtained through active surveillance provided timelier and more complete information. Clopidogrel-associated TTP often occurs within 2 weeks of drug initiation, occasionally relapses, and has a high mortality if not treated promptly.
Zakarija
Anaadriana
A
VA Chicago Healthcare System, VA Midwest Center for Health Services and Policy Research, Division of Hematology/Oncology, Department of Medicine, Northwestern University Medical Center, Chicago, Ill ., USA.
Bandarenko
Nicholas
N
Pandey
Dilip K
DK
Auerbach
Amy
A
Raisch
Dennis W
DW
Kim
Benjamin
B
Kwaan
Hau C
HC
McKoy
June M
JM
Schmitt
Brian P
BP
Davidson
Charles J
CJ
Yarnold
Paul R
PR
Gorelick
Philip B
PB
Bennett
Charles L
CL
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000368:Aged; D000369:Aged, 80 and over; D015984:Causality; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010951:Plasma Exchange; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D011358:Product Surveillance, Postmarketing / Q000706:statistics & numerical data*; D011379:Prognosis; D011697:Purpura, Thrombotic Thrombocytopenic / Q000139:chemically induced* / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D012008:Recurrence; D015996:Survival Rate; D013988:Ticlopidine / Q000009:adverse effects* / Q000031:analogs & derivatives*; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine