Assessment of the Impact of l-Thyroxine Therapy on Bleeding Risk in Patients Receiving Vitamin K Antagonists
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Several studies have suggested a link exists between l-thyroxine and the coagulation system, and, according to some drug interaction studies, l-thyroxine can potentiate the effect of warfarin. This study sought to assess whether thyroid hormone therapy could impact the risk of bleeding in patients receiving vitamin K antagonists (VKAs).
We conducted a monocentric, retrospective study on prospectively collected data from consecutive patients enrolled in the Registry of patient with AntiThrombotic agents admitted to an Emergency Department (RATED) database, and compared the hemorrhage rates (both major and nonmajor) of patients receiving treatment with and without l-thyroxine. Propensity score matching analysis was performed to reduce the differences between patients receiving l-thyroxine and those not receiving l-thyroxine in order to reassess bleeding outcomes in patients receiving VKAs.
From January 2014 to June 2015, 1454 patients receiving VKAs were recruited into the RATED database. Overall, 187 patients (12.8%) received l-thyroxine. Patients receiving l-thyroxine were more likely to be female than those not receiving l-thyroxine (78.1 vs. 55%) and more likely to exhibit hypertension (65.5 vs. 55.7%; p = 0.015), but less likely to have history of myocardial infarction (9.6 vs. 16.6%; p = 0.022) or higher creatinine levels (96.1 vs. 112.1 μmol/L; p = 0.04). After propensity score matching, bleeding outcomes were not significantly different between patients receiving l-thyroxine and those not receiving l-thyroxine.
Our study revealed no evidence that l-thyroxine could increase bleeding risk in patients receiving VKAs. However, physicians must be aware that patients with thyroid disease receiving VKA therapy could have other drug interactions, particularly with amiodarone therapy.
All authors had full access to all study data (including statistical reports and tables) and bear responsibility for data integrity and accuracy. In addition, all authors were involved in the critical revision of the manuscript with regard to its primary intellectual content, and approved the final version submitted for publication.
FM contributed to the design, analysis and interpretation of data, collected patients, and wrote the article. RM contributed to the interpretation of data, collected patients, and approved the final version of the article. BP contributed to statistical analysis and interpretation of data, and approved the final version of the article. AB contributed to the extraction of data and approved the final version of the article. JS-D contributed to the interpretation of data, collected patients, and approved the final version of the article. FD contributed to the interpretation of data, collected patients, and approved the final version of the article. MB contributed to the interpretation of data and approved the final version of the article. JS contributed to the design, analysis and interpretation of data, collected patients, and approved the final version of the article.
Compliance with Ethical Standards
Conflict of interest
Dr. Moustafa has served as a consultant for Bayer HealthCare Pharmaceuticals and Sanofi, has been a speaker for Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Daiichi-Sankyo and Sanofi, and has received grants from Sanofi, Bayer HealthCare, and LFB. Dr. Schmidt has received payments for board membership from Bayer, Daichi, Lilly, and Pfizer, as well as personal compensation from Biomerieux, Bohringer Ingelheim, Sanofi, and Novartis. Rémi Malhomme, Bruno Pereira, Alain Barres, Jennifer Saint-Denis, Frederic Dutheil, and Marie Batisse have no conflicts of interest relevant to the contents of this paper.
No specific grants were received from any funding agency in the public, commercial, or not-for-profit sectors for this research.
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