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Thromb Haemost 2013; 110(04): 723-731
DOI: 10.1160/TH13-04-0274
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

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

Jonathan Douxfils   *
1   Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Belgium
,
Anne Tamigniau   *
2   Laboratory of Clinical Chemistry, Saint-Luc University Hospital, Université Catholique de Louvain, Brussels, Belgium
,
Bernard Chatelain
3   Hematology Laboratory, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), CHU UCL Mont-Godinne-Dinant , Université Catholique de Louvain, Belgium
,
Christian Chatelain
4   Hematology Department, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), CHU UCL Mont-Godinne-Dinant , Université Catholique de Louvain, Belgium
,
Pierre Wallemacq
2   Laboratory of Clinical Chemistry, Saint-Luc University Hospital, Université Catholique de Louvain, Brussels, Belgium
,
Jean-Michel Dogné
1   Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Belgium
,
François Mullier   #
1   Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Belgium
3   Hematology Laboratory, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), CHU UCL Mont-Godinne-Dinant , Université Catholique de Louvain, Belgium
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Further Information

Publication History

Received: 03 April 2013

Accepted after major revision: 02 June 2013

Publication Date:
01 December 2017 (online)

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Summary

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 interindividual 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.

Keywords

Rivaroxaban - monitoring - prothrombin time - chromogenic anti-Xa assay - LC-MS/MS

* Contributed equally as first authors.


# Contributed equally as last authors.


 

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