Research into new anticoagulants for preventing and treating thromboembolic disorders has focused on targeting single enzymes in the coagulation cascade, particularly Factor Xa and thrombin, inhibition of which greatly decreases thrombin generation. Based on the results of phase III clinical trials, rivaroxaban, a direct Factor Xa inhibitor, has been approved in many countries for the management of several thromboembolic disorders. Owing to its predictable pharmacokinetic and pharmacodynamic characteristics, fixed-dose regimens are used without the need for routine coagulation monitoring. In situations where assessment of rivaroxaban exposure may be helpful, anti-Factor Xa chromogenic assays (in tandem with standard calibration curves generated with the use of rivaroxaban calibrators and controls) could be used. It is important to note that test results will be affected by the timing of blood sampling after rivaroxaban intake. In addition, the anti-Factor Xa method measures the drug concentration and not the intensity of the drug’s anticoagulant activity, and a higher than expected rivaroxaban plasma level does not necessarily indicate an increased risk of bleeding complications. Therefore, clinicians need to consider test results in relation to the pharmacokinetics of rivaroxaban and other patient risk factors associated with bleeding.

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Background Rivaroxaban is widely used in clinical practice. Although routine coagulation monitoring is not required, quantitative determination of rivaroxaban might be valuable in certain clinical circumstances. Variation in response sensitivity of prothrombin time (PT) reagents to rivaroxaban is well described in the literature, and the conventional international normalised ratio cannot be used for rivaroxaban. Purpose This multicentre study assessed the intra and interlaboratory precision of measurements of rivaroxaban plasma concentrations using the PT assay together with rivaroxaban calibrators and controls. Materials and methods Participating laboratories (Europe and North America) were provided with rivaroxaban calibrators (0, 41, 219 and 430 ng/ml), rivaroxaban pooled human plasma controls (19, 160 and 643 ng/ml) and PT reagent. Evaluation was performed over 10 consecutive days by each laboratory using local PT reagents as well as the centrally provided PT reagent (STA Neoplastine CI Plus; Diagnostica Stago). A calibration curve was produced each day, and day-to-day precision was evaluated by testing three control plasma samples. The control was diluted and re-tested if the level was above the highest concentration of the calibration curve. Results Intralaboratory variations in PT were dependent on the sensitivity of the local PT reagents, regardless of the type of instrument used. A large inter-laboratory variation (in seconds) was observed with local PT reagents; the coefficient of variation (CV) was 13.6–29.7%. When the results were expressed as rivaroxaban concentration (ng/ml), the inter-reagent variations were reduced; less variation was found with both local reagents (CV: 5.1–15.5%) and the central reagent (CV: 2.2–7.5%). However, over-estimation was observed with both local and central reagents. The CV for the calibrator containing 41 ng/ml rivaroxaban was 5.8% when the central reagent was used. Conclusions The PT assay may be useful for measuring rivaroxaban peak plasma concentrations (2–3 h after drug intake) using rivaroxaban calibrators and controls.

Introduction Directs oral anticoagulants (DOACs) can interfere with coagulation assays, especially in thrombophilia workup. To avoid these interferences, a new device, DOAC Filter, allows the removal of DOACs from citrated plasma. This study aims to confirm that DOAC Filter efficiently removes DOACs and to ascertain that coagulation assays are not impacted by filtration. Methods Directs oral anticoagulants Filter (Diagnostica Stago, France) is a filtration cartridge in which DOAC molecules are trapped by noncovalent binding, while plasma is filtered through a solid phase. Normal pool plasma (NPP) spiked with DOACs up to 300 ng/mL, with dabigatran etexilate (n = 27), rivaroxaban (n = 35), apixaban (n = 33), and edoxaban (n = 27) or 120 ng/mL for betrixaban (n = 4), and 18 plasma's samples from DOAC‐treated patients were used to assess efficacy. The potential impact of DOAC Filter on coagulation assays was evaluated with NPP and plasma's samples from positive and negative lupus anticoagulant (LA) patients. Results Directs oral anticoagulants concentrations measured after filtration were below the limit of detection (LoD) of DOAC‐specific assays for all plasmas tested, except for one apixaban plasma sample, with postfiltration concentration slightly higher than anti‐Xa assay LoD (25.1 ng/mL). Coagulation assays results varied between −4 and +8% after filtration and between −6 and +8% for LA plasmas. Such limited variations are not expected to have any clinical impact. Conclusion Directs oral anticoagulants Filter efficiently removes DOACs from plasma and achieves concentrations below DOAC‐specific assays LoD, except in the case of one apixaban sample. The integrity of plasma is respected, and the cartridge seems not to impact LA diagnosis.

Rivaroxaban is an oral, direct factor Xa inhibitor. Routine coagulation monitoring is not required, but a quantitative determination of rivaroxaban concentrations might be useful in some clinical circumstances. This multicentre study assessed the suitability of the anti-factor Xa chromogenic assay for the measurement of rivaroxaban plasma concentrations (ng/ml) using rivaroxaban calibrators and controls, and the inter-laboratory precision of the measurement. Twenty-four centres in Europe and North America were provided with sets of rivaroxaban calibrators (0, 41, 209 and 422 ng/ml) and a set of rivaroxaban pooled human plasma controls (20, 199 and 662 ng/ml; the concentrations were unknown to the participating laboratories). The evaluation was carried out over 10 days by each laboratory using local anti-factor Xa reagents as well as the centrally provided reagent, a modified STA® Rotachrom® assay. A calibration curve was produced each day, and the day-to-day precision was evaluated by testing three human plasma controls. When using the local anti-factor Xa reagents, the mean rivaroxaban concentrations (measured/actual values) were: 17/20, 205/199 and 668/662 ng/ml, and the coefficient of variance (CV) was 37.0%, 13.7% and 14.1%, respectively. When the modified STA Rotachrom method was used, the measured/actual values were: 18/20, 199/199 and 656/662 ng/ml, and the CV was 19.1%, 10.9% and 10.0%, respectively. The results suggest that, by using rivaroxaban calibrators and controls, the anti-factor Xa chromogenic method is suitable for measuring a wide range of rivaroxaban plasma concentrations (20-660 ng/ml), which covers the expected rivaroxaban plasma levels after therapeutic doses.