Hematologic dyscrasia associated with ticlopidine therapy: evidence for causality.
BACKGROUND
Several rare, potentially fatal types of hematologic dyscrasia, such as agranulocytosis, aplastic anemia, neutropenia, pancytopenia, thrombocytopenia and thrombotic thrombocytopenic purpura (TTP), have been associated with ticlopidine therapy. The extent to which ticlopidine is the causative factor has not been addressed quantitatively.


METHODS
We identified 211 published case reports of hematologic dyscrasia associated with ticlopidine therapy from a MEDLINE search. We analyzed the 91 reports that could be evaluated, using the Bayesian Adverse Reaction Diagnostic Instrument to calculate the posterior probability that ticlopidine caused the hematologic dyscrasia based on epidemiologic and clinical trial data (prior odds) and case information (likelihood ratio).


RESULTS
The median posterior probability values (and range) for agranulocytosis, aplastic anemia, neutropenia, pancytopenia, thrombocytopenia and TTP were 0.95 (0.53-0.98), 0.81 (0.57-0.93), 0.86 (0.75-0.96), 0.78 (0.61-0.89), 0.74 (0-0.92) and 1.0 (0.33-1.00) respectively. The posterior probability was 0.75 or greater in 82 (90%) of the case reports.


CONCLUSIONS
This systematic analysis provides stronger evidence to implicate ticlopidine as the causative factor in the various types of hematologic dyscrasia in most published case reports.
Paradiso-Hardy
F L
FL
Department of Pharmacy, Divisions of Cardiology and Clinical Pharmacology, Sunnybrook & Women's College Health Sciences Centre, Faculty of Pharmacy, University of Toronto, Toronto, Ont. fran.paradiso-hardy@swchsc.on.ca
Angelo
C M
CM
Lanctôt
K L
KL
Cohen
E A
EA
D001499:Bayes Theorem; D004305:Dose-Response Relationship, Drug; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced* / Q000145:classification; D006801:Humans; D008297:Male; D009503:Neutropenia / Q000139:chemically induced*; D016017:Odds Ratio; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D013988:Ticlopidine / Q000009:adverse effects*
D010975:Platelet Aggregation Inhibitors; D013988:Ticlopidine