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Thrombotic thrombocytopenic purpura associated with clopidogrel: further evaluation
Fran L Paradiso-Hardy1, John Papastergiou, Krista L Lanctôt
1Schulich Heart Program, Department of Pharmacy and HOPE Research Centre, Sunnybrook Women's College Health Sciences Centre, Toronto, Ontario. fran.paradiso-hardy@swchs.on.ca
Insights
Clopidogrel was linked to thrombotic thrombocytopenic purpura (TTP) in some cases. A Bayesian analysis suggests clopidogrel caused TTP in 5 of 11 reported instances.
Area of Science:
- Pharmacovigilance
- Hematology
- Drug Safety
Background:
- Thrombotic thrombocytopenic purpura (TTP) is a rare but serious condition.
- Eleven cases of TTP potentially linked to clopidogrel therapy have been documented.
Purpose of the Study:
- To quantitatively assess the causal relationship between clopidogrel and TTP.
- To determine the extent to which clopidogrel was the causative agent in published TTP cases.
Main Methods:
- Bayesian Adverse Reaction Diagnostic Instrument used for causality assessment.
- Analysis incorporated epidemiological data, clinical trial results, and case-specific clinical characteristics.
- Posterior probability (PsP) calculated to quantify clopidogrel's role.
Main Results:
- Clopidogrel was identified as the causative factor (PsP > 0.75) in 5 out of 11 TTP cases.
- Concomitant statin use, cancer history, and relapsing TTP lowered the PsP in the remaining 6 cases.
- The analysis provided quantitative evidence for clopidogrel's involvement.
Conclusions:
- Strong evidence suggests clopidogrel is a causative factor in some TTP cases.
- The study highlights the importance of systematic causality assessment in adverse drug reactions.
- Further investigation into clopidogrel-associated TTP is warranted.
Background:
Eleven cases of thrombotic thrombocytopenic purpura (TTP) associated with clopidogrel therapy have been published.
Objectives:
To perform a comprehensive causality assessment of the 11 published cases of TTP to assess quantitatively the extent to which clopidogrel was the causative factor.
Methods:
The 11 reports of TTP were analyzed using the Bayesian Adverse Reaction Diagnostic Instrument to calculate the posterior probability (PsP) that clopidogrel caused the TTP based on epidemiological and clinical trials data (expressed as prior odds) and the clinical characteristics of each case (expressed as likelihood ratios).
Results:
Clopidogrel was implicated as the causative factor of the TTP (PsP>0.75) in only five of the 11 cases. The PsP for clopidogrel was lowered by concomitant use of a statin, a history of cancer and the occurrence of relapsing TTP (in the absence of clopidogrel) in the remaining six cases.
Conclusions:
This systematic analysis provides strong evidence, based on the case information reported, that clopidogrel was the causative factor in at least some cases of TTP.