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Drug-induced disseminated intravascular coagulation: a pharmacovigilance study on World Health Organization’s database

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Abstract

Background

Disseminated intravascular coagulation (DIC) occurs in several clinical conditions, including drug therapy. We aim to investigate the association between the administration of several drug classes and the onset of DIC by using the reports of Adverse Drug Reactions (ADR) collected in Vigibase, the World Health Organization (WHO) database of ADR.

Methods

We collected reports of drug-related DIC from 1968 to September 2015, classified in Vigibase according to the MedDRA (Medical Dictionary for Regulatory Activities) term “Disseminated intravascular coagulation”. A disproportionality analysis using Reporting Odds Ratio (ROR) with 95% Confidence Interval (CI95%) was performed.

Results

Overall, 4653 reports of drug-associated DIC were retrieved and the 75.9% of them was serious according to WHO seriousness criteria. DIC was significantly (ROR > 1, lower limit of CI95% > 1) associated with 88 drugs, mainly antineoplastic agents, antithrombotic agents and antibacterials for systemic use. Among of the most frequently reported individual drugs we found dabigatran (94 reports) ROR = 1.34 (CI95% 1.08–1.67), oxaliplatin and bevacizumab both with 75 reports and ROR = 1.77 (1.38–2.27) and 2.02 (1.57–2.61), respectively.

Conclusion

A substantial number of drugs, widely used in the clinical practice, may be associated with the potential occurrence of DIC. For many of these drugs, the ADR is not acknowledged in the corresponding Summary of Product Characteristics. The high number of drugs involved underlines the importance of evaluate this condition such as an ADR that might occur during drug therapy.

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Acknowledgements

We are grateful to the Uppsala Monitoring Centre—WHO Collaborating Centre for International Drug Monitoring for providing data. The information comes from a variety of sources, and the likelihood that the suspected adverse reaction is drug-related is not the same in all cases. The information does not represent the opinion of the World Health Organization. We would like to thank Mauro Venegoni, MD, for his authoritative and helpful comments to the manuscript and Laura Rossi, PharmD, who participated in this research when preparing her graduation thesis at the Unit of Pharmacology, University of Bologna.

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Conceptualization, GB, AV and DM; Data curation, MM; Formal analysis, GB, AV, MM, DM; Investigation, GB, DM; Methodology, GB, DM, MM; Supervision, AV; Validation, MM; Writing—original draft, GB, DM; Writing—review & editing, GB, AV, MM, DM.

Corresponding author

Correspondence to Giulia Bonaldo.

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Bonaldo, G., Vaccheri, A., Melis, M. et al. Drug-induced disseminated intravascular coagulation: a pharmacovigilance study on World Health Organization’s database. J Thromb Thrombolysis 50, 763–771 (2020). https://doi.org/10.1007/s11239-020-02147-y

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