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, throm bocytopenia and thrombotic thrombocytopenic purpura (TTP), have been associ ated with ticlopidine therapy. The extent to which ticlopidine is the causa tive 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 Dia gnostic 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 agranulocy tosis, 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 probabilit y was 0.75 or greater in 82 (90%) of the case reports. Interpretation: This systematic analysis provides stronger evidence to impl icate ticlopidine as the causative factor in the various types of hematolog ic dyscrasia in most published case reports.