Ex vivo reversal of effects of rivaroxaban evaluated using thromboelastometry and thrombin generation assay B. Schenk, P. Würtinger, W. Streif, W. Sturm,

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Ex vivo reversal of effects of rivaroxaban evaluated using thromboelastometry and thrombin generation assay B. Schenk, P. Würtinger, W. Streif, W. Sturm, D. Fries, M. Bachler British Journal of Anaesthesia Volume 117, Issue 5, Pages 583-591 (November 2016) DOI: 10.1093/bja/aew259 Copyright © 2016 The Author(s) Terms and Conditions

Fig 1 Correlation between various coagulation parameters and rivaroxaban plasma concentrations. Whole blood from healthy volunteers (n=13) was spiked with various doses of rivaroxaban (100–700 ng ml−1). Significantly (P<0.05 for all) correlated parameters were as follows: (a) thromboelastometry EXTEM clotting time (CT, linear approximation for CT=47.7+51.1x); (b) thromboelastometry EXTEM time to maximal velocity (MaxV−t, linear approximation for MaxV−t=196.6+30.5x); (c) thrombin generation lag time (tlag, linear approximation for tlag=24.3+9.5x); (d) thrombin generation time to peak (tmax, linear approximation for tmax=25.7+27.2x); (e) thrombin generation area under the curve (AUC, linear approximation for AUC=314.5−8.5x); and (f) thrombin generation maximum of thrombin potential [Cmax, logarithmic approximation for Cmax=114.8–78.2×log10(x)]. X refers to the respective value on the x-axis. The strength of correlation was interpreted by evaluating the correlation coefficient, as follows: r 0.9−1.0 (−0.9 to −1.0)=very strong correlation; r 0.7–0.89 (−0.7 to −0.89)=strong correlation; r 0.5–0.69 (−0.5 to −0.69)=moderate correlation; and r 0.3–0.49 (−0.3 to −0.49)=weak correlation. British Journal of Anaesthesia 2016 117, 583-591DOI: (10.1093/bja/aew259) Copyright © 2016 The Author(s) Terms and Conditions

Fig 2 Ex vivo reversal of rivaroxaban-induced prolonged EXTEM clotting time (CT, in seconds) with potential non-specific reversal agents. Blood samples from patients on rivaroxaban (n=18, obtained 3 h after last medication intake) were defined as baseline values. Normal values (healthy persons without anticoagulation) of EXTEM CT are indicated (blue area). Blood samples were spiked with various non-specific reversal agents, as follows: fibrinogen concentrate (FI; FGTW, 0.6 or 3 mg ml−1), prothrombin complex concentrate (PCC; Beriplex®, 0.3 or 1 U ml−1), activated prothrombin complex concentrate (aPCC; FEIBA, 1.5 or 2.25 U ml−1), and recombinant activated factor VII (rFVIIa; NovoSeven®, 1.5 or 4.05 µg ml−1). Reversal from baseline was determined using Wilcoxon signed-rank test (*P<0.05). British Journal of Anaesthesia 2016 117, 583-591DOI: (10.1093/bja/aew259) Copyright © 2016 The Author(s) Terms and Conditions