A universal anti-Xa assay for the determination of rivaroxaban, apixaban, and edoxaban drug levels: development, diagnostic accuracy, and external validation

Objective A universal anti-Xa assay for the determination of rivaroxaban, apixaban, and edoxaban drug levels would simplify laboratory procedures and facilitate widespread implementation. We aimed to develop and validate a universal anti-Xa assay to be used in clinical practice.

Material and Methods Following two pilot studies analyzing spiked samples and material from 625 patients, we conducted a prospective multicentre cross-sectional study, including 867 patients treated with rivaroxaban, apixaban, or edoxaban in clinical practice. Anti-Xa activity was measured by a universal assay calibrated to low-molecular weight heparin (LMWH) in addition to ultra‐performance liquid chromatography–tandem mass spectrometry (LC-MS/MS). As an external validation, anti-Xa activity was also determined in nine external laboratories.

Results Measurements of the universal anti-Xa assay correlated strongly with rivaroxaban, apixaban, or edoxaban drug levels (rs=0.94, 95% confidence interval, CI, 0.93 to 0.99; area under the receiver operating characteristics curve, AUC, 0.99). The sensitivity with regard to the clinically relevant cut-off levels 30 µg/L and 50 µg/L was 96.2% (95% CI 94.4, 97.4) and 96.4% (94.4, 97.7), respectively (specificity 92.9% and 93.3%). Concordant results were obtained in the external validation study (rs=0.96; AUC 0.98; sensitivity 95.78% and 97.44%; specificity 85.94% and 97.44%).

Conclusion The universal anti-Xa assay based on an LWMH-calibration demonstrated a high accuracy in all phases of the evaluation project. Widespread implementation might simplify laboratory procedures and provide fast and reliable drug measurements in various healthcare settings.

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Publication History

Article published online:
18 June 2021