Comparison of calibrated chromogenic anti-Xa assay and PT tests with LC-MS/MS for the therapeutic monitoring of patients treated with rivaroxaban.

Douxfils, J;Tamigniau, A;Chatelain, Bernard;Chatelain, Christian;Mullier, François;et.al.
(2013) Thrombosis and Haemostasis : international journal for vascular biology and medicine — Vol. 110, n° 4, p. 723-731 (2013)

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Authors
  • Douxfils, J
    Author
  • Tamigniau, A
    Author
  • Chatelain, BernardUCLouvain
    Author
  • Chatelain, ChristianUCLouvain
    Author
  • Mullier, FrançoisUCLouvain
    Author
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Abstract
Possibilities to monitor rivaroxaban therapy could be useful in certain circumstances. Prothrombin time (PT) or chromogenic anti-Xa assays such as the Biophen Direct Factor Xa Inhibitor® (DiXaI) have been proposed to estimate rivaroxaban concentrations but are mainly based on in vitro studies. The study aim was to compare PT and Biophen DiXaI® measurements with liquid chromatography-tandem mass spectrometry (LC-MS/MS) measurements in plasma samples from patients treated with Xarelto®. Fifty-two plasma samples were included. PT was performed using Innovin® and Triniclot PT Excel S®. Biophen DiXaI® was performed according to instructions from the manufacturer. The rivaroxaban plasma concentration ranged between 0 and 485 ng/ml as measured by LC-MS/MS. The limits of quantification were 30 ng/ml and 5 ng/ml for Biophen DiXaI® and LC-MS/MS, respectively. The linear correlation between Biophen DiXaI® and LC-MS/MS analyses was high for all rivaroxaban concentrations (r² = 0.95). For concentrations ≤100 ng/ml, r²-value was 0.83. The Bland-Altman analysis showed a mean difference of -16 ng/ml (SD: 25 ng/ml). The PT methods did not correlate well with plasma concentrations measured by LC-MS/MS (r² ≍ 0.60). In conclusion, the important inter-individual variability and the poor correlation with LC-MS/MS preclude the use of PT to estimate rivaroxaban concentrations. Thanks to its small inter-individual variability and good agreement with LC-MS/MS measurements, we recommend the use of Biophen DiXaI® assays to estimate concentrations of rivaroxaban >30 ng/ml. Quantification of low rivaroxaban levels (<30 ng/ml) requires the LC-MS/MS method.
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Douxfils, J., Tamigniau, A., Chatelain, B., Chatelain, C., Wallemacq, P., Dogné, J.-M., & Mullier, F. (2013). Comparison of calibrated chromogenic anti-Xa assay and PT tests with LC-MS/MS for the therapeutic monitoring of patients treated with rivaroxaban. Thrombosis and Haemostasis : international journal for vascular biology and medicine, 110(4), 723-731. https://doi.org/10.1160/TH13-04-0274 (Original work published 2013)