Is anti-factor Xa chromogenic assay for Rivaroxaban appropriate in clinical practice? Advantages and comparative drawbacks

Bardy, Guillaume; Fischer, Florence; Appert, Anny; Baldin, Bernadette; Stève, Marie; Spreux, A; Lavrut, Thibaud; Drici, Milou‐Daniel

doi:10.1016/j.thromres.2015.05.015

Cited by 17 publications

(12 citation statements)

References 27 publications

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“…Several previous studies investigated the correlation of anti‐Xa results with known rivaroxaban plasma concentrations determined by dilution studies or liquid chromatography‐tandem mass spectrometry (LC‐MS) . In line with these, correlation coefficients in our study were also high.…”

Section: Discussionsupporting

confidence: 85%

“…The variability of results was significant between individuals but low within individuals. Several previous studies investigated the correlation of anti-Xa results with known rivaroxaban plasma concentrations determined by dilution studies [15] or liquid chromatography-tandem mass spectrometry (LC-MS) [12,[16][17][18][19][22][23][24][25]. In line with these, correlation coefficients in our study were also high.…”

Section: Discussionsupporting

confidence: 83%

“…2). This was unexpected, but could be anticipated from previous publications [16,17,22,24]. By contrast, one publication reported an opposite effect with a negative bias of the Bland-Altman difference plot and a slope of the regression line just below one [19].…”

Section: Discussionmentioning

confidence: 59%

“…Spiked samples were used to assess the correlation with known rivaroxaban plasma concentrations, determined by dilution techniques or high-pressure liquid chromatography-tandem mass spectrometry (HPLC-MS) [12,14,15]. The correlation of anti-Xa activity and rivaroxaban plasma concentration has also been studied in samples of patients or healthy volunteers [16][17][18][19][20][21][22][23][24][25]. However, important issues such as the reproducibility between laboratories, the consistency between different reagents and analyzers, as well as the variability within and between individuals, have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Accuracy and consistency of anti‐Xa activity measurement for determination of rivaroxaban plasma levels

Studt

Alberio

Angelillo‐Scherrer

et al. 2017

Journal of Thrombosis and Haemostasis

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Background Determining the plasma level of direct oral anticoagulants reliably is important in the work-up of complex clinical situations. Objectives To study the accuracy and consistency of anti-Xa assays for rivaroxaban plasma concentration in a prospective, multicenter evaluation study employing different reagents and analytical platforms. Methods Rivaroxaban 20 mg was administered once daily to 20 healthy volunteers and blood samples were taken at peak and trough levels (clinicaltrials.gov NCT01710267). Anti-Xa activity was determined in 10 major laboratories using different reagents and analyzers; corresponding rivaroxaban plasma concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS). Findings Overall Pearson's correlation coefficient of anti-Xa levels and HPLC-MS results was 0.99 for Biophen Heparin (95% CI, 0.99, 0.99), Biophen DiXaI (95% CI, 0.99, 0.99) and STA anti-Xa liquid (95% CI, 0.99, 1.00). Correlation was lower in rivaroxaban concentrations below 50 μg L and above 200 μg L . The overall bias of the Bland-Altman difference plot was 14.7 μg L for Biophen Heparin, 17.9 μg L for Biophen DiXal and 19.0 μg L for STA anti-Xa liquid. Agreement between laboratories was high at peak level but limited at trough level. Conclusions Anti-Xa activity correlated well with rivaroxaban plasma concentrations, especially in a range between 50 and 200 μg L . However, anti-Xa assays systematically overestimated rivaroxaban concentration as compared with HPLC-MS, particularly at higher concentrations. This overestimation, coupled with an apparent interindividual variation, might affect the interpretation of results in some situations.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

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Accuracy and consistency of anti‐Xa activity measurement for determination of rivaroxaban plasma levels

Studt

Alberio

Angelillo‐Scherrer

et al. 2017

Journal of Thrombosis and Haemostasis

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“…Not all the anti‐Xa assays tested in our study were previously evaluated in published works for quantification of apixaban or rivaroxaban concentrations. The six methods not supplemented with exogenous antithrombin showed LOD and LOQ values ranging from 3‐16 ng/mL and 8‐39 ng/mL, respectively, comparable to the available published data [LOD from 11 to 29 ng/mL (DiXaI‐HY, LRT‐HY, AntiXa‐STA) and LOQ from 6 to 52 ng/mL (DiXaI‐HY, LRT‐HY, AntiXa‐STA, AntiXa‐TC)] . The HPLC‐UV method showed good LOD and LOQ for apixaban and rivaroxaban (LOD from 5 to 9 ng/mL and LOQ from 16 to 29 ng/mL), comparable to values reported in literature (LOD from 4 to 5 ng/mL and LOQ from 10 to 19 ng/mL) …”

Section: Discussionsupporting

confidence: 77%

DOAC plasma levels measured by chromogenic anti‐Xa assays and HPLC‐UV in apixaban‐ and rivaroxaban‐treated patients from the START‐Register

Cini¹,

Legnani²,

Padrini

et al. 2020

Int J Lab Hematology

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Introduction To measure direct factor Xa inhibitor (apixaban, edoxaban, rivaroxaban) concentrations, dedicated chromogenic anti‐Xa assays are recommended as suitable methods to provide rapid drug quantification. Moreover, the high‐performance liquid chromatography with ultraviolet detection (HPLC‐UV) is reported as a reliable quantitative technique. We investigated seven anti‐Xa assays and an HPLC‐UV method for measurement of apixaban and rivaroxaban levels in patients enrolled in the START‐Register. Methods A total of 127 apixaban and 124 rivaroxaban samples were tested by HPLC‐UV and the following anti‐Xa assays: Biophen DiXaI and Heparin LRT (Hyphen BioMed), Berichrom and Innovance Heparin (Siemens), STA‐Liquid Anti‐Xa (Stago Diagnostics), Technochrom anti‐Xa (Technoclone), and HemosIL Liquid Anti‐Xa (Werfen). Each method was performed in one of the participating laboratories: Bologna, Cremona, Florence, and Padua. Results Our data confirmed the overestimation of apixaban and rivaroxaban levels by the antithrombin‐supplemented anti‐Xa method (Berichrom). Performances and reproducibility of the six anti‐Xa assays not supplemented with antithrombin and the HPLC‐UV method were good, with limits of quantification from 8‐39 ng/mL (apixaban) and 15‐33 ng/mL (rivaroxaban). The six chromogenic methods showed good concordances with the quantitative HPLC‐UV [bias: −26.9‐22.3 ng/mL (apixaban), −11.3‐18.7 ng/mL (rivaroxaban)]. Higher bias and wider range between limits of agreement were observed at higher concentrations [<100 ng/mL: bias −21.3‐4.1 ng/mL (apixaban) and −6.2‐3.8 ng/mL (rivaroxaban); >200 ng/mL: bias −42.2‐36.8 ng/mL (apixaban) and −20.1‐68.9 ng/mL (rivaroxaban)]. Conclusion Overall, the anti‐Xa assays not supplemented with antithrombin and the HPLC‐UV method proved to be suitable for apixaban and rivaroxaban quantification.

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Understanding Advanced Hematologic Testing

Schmidt

Marques

2018

Hematologic Challenges in the Critically Ill

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Is anti-factor Xa chromogenic assay for Rivaroxaban appropriate in clinical practice? Advantages and comparative drawbacks

Cited by 17 publications

References 27 publications

Accuracy and consistency of anti‐Xa activity measurement for determination of rivaroxaban plasma levels

Accuracy and consistency of anti‐Xa activity measurement for determination of rivaroxaban plasma levels

DOAC plasma levels measured by chromogenic anti‐Xa assays and HPLC‐UV in apixaban‐ and rivaroxaban‐treated patients from the START‐Register

Understanding Advanced Hematologic Testing

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