Use of a Universal Calibrator for Direct FXa inhibitor DOACs

Objective Increasing use of direct oral anticoagulants has led to rising numbers of requests for drug level measurement in routine laboratories. Although the same test is used, the anti-Xa assay, individual calibrator and control sets are required for each direct FXa inhibitor (DFXaI). The study was designed to test the usability of a single calibrator set with assigned values for edoxaban, rivaroxaban and apixaban.

Material and Methods A calibrator set composed of normal pooled plasma spiked with different levels of edoxaban was assigned calibrated values for edoxaban, rivaroxaban and apixaban traceable to LC-MS/MS of each DFXaI. On the new Ceveron c100 automated analyzer, TECHNOCHROM® anti-Xa assay was calibrated using the universal calibrator set separately for each DFXaI. For all drugs a high and low range application using different plasma pre-dilutions can be employed. Plasma samples from patients receiving one of the respective drugs were assessed using the appropriate LC-MS/MS method and TECHNOCHROM® anti-Xa assay calibrated for the respective drug.

Results DFXaI-specific calibration curves were established using standard Ceveron c100 applications. As expected, correlation of anti-Xa determined edoxaban to mass spectrometry values for ex-vivo samples was 0.98. For ex-vivo rivaroxaban samples, Passing and Bablok regression between anti-Xa and LC-MS/MS exhibited a slope of 0.95 and intercept of <2 ng/mL (pearson r 0.95). Similarly, the regression for ex-vivo apixaban samples generated a slope of 1.1 and correlation of 0.94.

Conclusion Here we describe a universal calibrator set which can be used to calibrate respective applications for edoxaban, rivaroxaban and apixaban using a chromogenic anti-Xa assay on a routine coagulation analyser. In addition, a similar approach can be used for a universal anti-Xa control set. A universal calibrator and control set for all anti-Xa assays has potential to reduce the cost of DFXaI measurement and improve throughput without compromising quality and traceability.

Publication History

Article published online:
18 June 2021