Comparison of Methods to Determine Rivaroxaban anti-factor Xa activity

Rathbun, Suman; Tafur, Alfonso; Grant, Russell P.; Esmon, Naomi L.; Mauer, Karin; Marlar, Richard A.

doi:10.1016/j.thromres.2014.11.017

Cited by 42 publications

(40 citation statements)

References 13 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%

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%

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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“…Bland‐Altman analysis shows that larger differences are found in the calibrated PT with both reagents in comparison to HPLC‐MS/MS measurements as rivaroxaban concentrations increase (Douxfils et al , ). A separate ex‐vivo study shows similar correlation ( r = 0·77) between PT using Neoplastine reagent (Stago Diagnostica) and HPLC‐MS/MS (Rathbun et al , ). However, rivaroxaban levels ranging from 0 to 127·4 ng/ml as measured by HPLC‐MS/MS produce short prolongation in PT (INR < 1·2).…”

Section: Rivaroxabanmentioning

confidence: 74%

Laboratory measurement of the direct oral anticoagulants

2015

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Direct oral anticoagulants (DOACs), including the direct thrombin inhibitor, dabigatran, and the direct factor Xa (FXa) inhibitors, rivaroxaban, apixaban and edoxaban, are approved for thromboembolism prevention and treatment. These drugs do not require routine coagulation monitoring but, in some circumstances, measurement of drug level or anticoagulant effect may be necessary. Although traditional coagulation tests lack analytical sensitivity and specificity, they are widely available and inexpensive, and can provide useful information regarding the residual anticoagulant effect of DOACs. Hemoclot® and ecarin-based assays can be used to quantify dabigatran level and calibrated chromogenic anti-FXa assays are suitable for measuring rivaroxaban, apixaban and edoxaban levels, but these tests are not yet widely available.

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“…). Other methods for quantifying or estimating drug concentrations have been described for use in patients with a known history of DOAC use, including dilute Russell's viper venom time (DRVVT) , modified PT , point‐of‐care methods , chromogenic anti‐FXa , thrombin generation assays , and thromboelastometry , but all lack specificity for DOACs, which limits their use as a screening or quantifying method. Urinary methods for measuring the metabolites of dabigatran or rivaroxaban offer interesting alternatives to blood testing, but these methods do not correlate with the concentration of drug in the blood, and their results should be interpreted with caution .…”

Section: The Clinical Question: Is a Doac Present?mentioning

confidence: 99%

The laboratory's 2015 perspective on direct oral anticoagulant testing

Gosselin

Adcock

2016

Journal of Thrombosis and Haemostasis

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Summary. The introduction of direct oral anticoagulant (DOAC) therapy into clinical use in the past 5 years has had significant impact on the clinical laboratory. Clinicians' desire to determine plasma drug presence or measure drug concentration, and more recent observations regarding the limitations and utility of coagulation testing in the setting of DOAC treatment, suggest that early published recommendations regarding laboratory testing should be reassessed. These initial recommendations, furthermore, were often based on drug-spiked plasma studies, rather than samples from patients receiving DOAC therapy. We have demonstrated that reagent sensitivity varies significantly whether drug-spiked samples or samples from DOAC-treated patients are tested. Data from drug-enriched samples must therefore be interpreted with caution or be used as a guide only. We present laboratory assays that can be used to determine drug presence and to measure drug concentration, and provide recommended testing algorithms. As DOAC therapy may significantly impact on specialty coagulation assays, we review those tests with the potential to give false-positive and false-negative results.

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Comparison of Methods to Determine Rivaroxaban anti-factor Xa activity

Cited by 42 publications

References 13 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

Laboratory measurement of the direct oral anticoagulants

The laboratory's 2015 perspective on direct oral anticoagulant testing

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