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. 2023 Jun 20;13(12):2128.
doi: 10.3390/diagnostics13122128.

Determination of Anti-Xa Inhibitor Plasma Concentrations Using a Universal Edoxaban Calibrator

Annika Burger  1 , Jan-Dirk Studt  2 , Adriana Mendez  3 , Lorenzo Alberio  4 , Pierre Fontana  5 , Walter A Wuillemin  6 , Adrian Schmidt  7 , Lukas Graf  8 , Bernhard Gerber  9 , Cédric Bovet  1 , Thomas C Sauter  10 , Nikolaus B Binder  11 , Michael Nagler  1
Affiliations

Determination of Anti-Xa Inhibitor Plasma Concentrations Using a Universal Edoxaban Calibrator

Annika Burger et al. Diagnostics (Basel). .

Abstract

A universal calibrator for the determination of all anti-Xa inhibitors would support laboratory processes. We aimed to test the clinical performance of an anti-Xa assay utilizing a universal edoxaban calibrator to determine clinically relevant concentrations of all anti-Xa inhibitors. Following a pilot study, we enrolled 553 consecutive patients taking rivaroxaban, edoxaban, or apixaban from nine study centers in a prospective cross-sectional study. The Technochrom® anti-Xa assay was conducted using the Technoview® edoxaban calibrator. Using ultra-high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), anti-Xa inhibitor drug concentrations were determined. Sensitivities and specificities to detect three clinically relevant drug concentrations (30 µgL-1, 50 µgL-1, 100 µgL-1) were determined. Overall, 300 patients treated with rivaroxaban, 221 with apixaban, and 32 with edoxaban were included. The overall correlation coefficient (rs) was 0.95 (95% CI 0.94, 0.96). An area under the receiver operating characteristic curve of 0.96 for 30 µgL-1, 0.98 for 50 µgL-1, and 0.99 for 100 µgL-1 was found. The sensitivities were 92.3% (95% CI 89.2, 94.6), 92.7% (89.4, 95.1), and 94.8% (91.1, 97.0), respectively (specificities 82.2%, 93.7%, and 94.4%). In conclusion, the clinical performance of a universal, edoxaban-calibrated anti-Xa assay was solid and most drug concentrations were predicted correctly.

Keywords: anti-Xa assay; anticoagulants introduction; apixaban; diagnostic accuracy; edoxaban; laboratory monitoring; rivaroxaban.

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Conflict of interest statement

MN reports research grants from Bayer Healthcare, outside of the submitted work, lecture honoraria from Bayer Healthcare, and Daiichi Sankyo. LA reports research grants from Bayer, CSL-Behring, Novartis, Novo Nordisk, Roche, Sobi, and Takeda. WAW reports research grants from Bayer Healthcare, BMS-Pfizer, Daiichi Sankyo, and Sanofi, and honoraria for participating in scientific advisory boards from Bayer, Pfizer, and from Alexion Pharma GmbH, all outside the submitted work. JDS reports lecture fees and advisory honoraria from Bayer Healthcare, Pfizer, Takeda, Siemens, and Sanofi. TCS holds an endowed professorship supported by the Touring Club Switzerland. BG reports non-financial support and funding for an accredited continuing medical education program from Axonlab, and from Thermo Fisher Scientific, during the conduct of the study; personal fees and funding for an accredited continuing medical education program from Alnylam; grants, personal fees and funding for accredited continuing medical education program from Pfizer; funding for an accredited continuing medical education program from Bayer, Bristol Myers Squibb, Daiichi-Sankyo, Takeda, Octapharma, SOBI, Janssen, Novo Nordisk, and Mitsubishi Tanabe Pharma, outside the submitted work. NBB is an employee and stakeholder of Technoclone.

Figures

Figure 1
Figure 1
The flow of the patients.
Figure 2
Figure 2
Scattergram showing the association between edoxaban-calibrated anti-Xa activity and the measurements of LC-MS/MS by drug. The overall correlation (rs) was 0.94 (95% CI 0.93, 0.95). It was 0.95 for rivaroxaban (95% CI 0.94, 0.96), 0.93 for apixaban (95% CI 0.91, 0.95), and 0.93 for edoxaban (95% CI 0.86, 0.97).
Figure 3
Figure 3
Distribution of edoxaban-calibrated anti-Xa measurements in patients with and without clinically relevant drug concentrations (30 µgL−1, 50 µgL−1, 100 µgL−1). The cut-off thresholds were determined using a receiver operating characteristics curve (ROC) analysis. The sensitivities were 92.3% (30 µgL−1; 95% CI 89.2, 94.6), 92.7% (50 µgL−1; 95% CI 89.4, 95.1), and 94.8% (100 µgL−1; 95% CI 91.1, 97.0). The specificities were 82.2% (95% CI 75.6, 87.3), 93.7% (95% CI 89.7, 96.2), and 94.4% (95% CI 91.3, 96.4).
Figure 4
Figure 4
Receiver operating characteristics curves demonstrating the diagnostic accuracy of an edoxaban-calibrated anti-Xa assay for the prediction of clinically relevant drug concentrations (30 µgL−1, 50 µgL−1, 100 µgL−1).
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