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Role of thromboelastography and rapid thromboelastography to assess the pharmacodynamic effects of vitamin K antagonists

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Abstract

Thromboelastography (TEG) measures the effects of antithrombotic agents by assessing global functional clotting status by evaluating the viscoelastic properties of in vitro clot formation. Recently, rapid TEG (r-TEG), which uses tissue factor in addition to standard kaolin to accelerate activation of the clotting cascade, has been proposed to obtain more immediate results. The correlation between results of TEG or r-TEG with international normalized ratio (INR) in patients on vitamin K antagonist (VKA) therapy has not been explored and represents the aim of this study. Patients on chronic therapy with VKAs (n = 100) were included in an observational prospective pharmacodynamic study. The correlation between TEG parameters, in particular markers of thrombus generation [Reaction time (R), maximum rate of thrombus generation (MRTG), and time to maximum rate of thrombus generation (TMRTG)], and INR values as well as the concordance between these parameters and therapeutic INR ranges were evaluated. In addition, in a subgroup of subjects (n = 17), the correlation of r-TEG parameters with TEG parameters and INR values was also assessed. No correlation was found between INR and TEG parameters of thrombus generation, in particular between INR and R (r = 0.189, p = 0.06), MRTG (r = −0.027, p = 0.79), and TMRTG (r = 0.188, p = 0.06). Further, no concordance was found between these parameters and recommended INR ranges. Significant Spearman correlations were found between INR and activated clotting time (rS = 0.546, p < 0.001), r-R (rS = 0.572, p = 0.017), and r-TMRTG (rS = 0.510, p = 0.037), but not r-MRTG (rS = 0.131, p = 0.617). Results were obtained in 24 ± 6 versus 12 ± 4 min with TEG and r-TEG, respectively (p < 0.001). In patients on chronic VKA therapy, TEG is not a useful tool to evaluate VKA anticoagulant effect, compared with standard INR measurements. However, r-TEG parameters of thrombus generation correlate with INR levels, suggesting a possible role of this assay for measuring more expeditiously anticoagulant treatment effects.

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Acknowledgments

This study was funded by an investigator sponsored Grant provided by Haemonetics Corporation (Braintree, MA, USA).

Conflict of interest

Dominick J. Angiolillo received payment as an individual for: (a) Consulting fee or honorarium from Bristol Myers Squibb, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, Merck, Evolva, Abbott Vascular, Bayer, and PLx Pharma; (b) Participation in review activities from Johnson & Johnson, St. Jude, and Sunovion. Institutional payments for Grants from Bristol Myers Squibb, Sanofi-Aventis, Glaxo Smith Kline, Otsuka, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, Evolva, and Gilead. Francesco Franchi, Syed Hammad Jafri, Fabiana Rollini, Antonio Tello-Montoliu, Ronakkumar Patel, Andrew Darlington, Dale F. Kraemer, Jung Rae Cho, Christopher DeGroat, Mona Bhatti, Mohamad Taha have no conflict of interest to report.

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Franchi, F., Hammad, J.S., Rollini, F. et al. Role of thromboelastography and rapid thromboelastography to assess the pharmacodynamic effects of vitamin K antagonists. J Thromb Thrombolysis 40, 118–125 (2015). https://doi.org/10.1007/s11239-014-1130-1

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