Abstract Number: PB0165
Meeting: ISTH 2020 Congress
Background: Currently, chromogenic anti-Xa assays are considered as the most appropriate assays to estimate the concentration of factor Xa inhibitors. Among them, edoxaban is the only compound for which some of the metabolites are reported to be pharmacologically actives. Although generally found at low concentrations, these metabolites could potentially interfere with chromogenic assays.
Aims: To assess the performance of several commercial chromogenic anti-Xa assays with a validated ultra-high-performance-liquid chromatography coupled with a tandem mass spectrometry (UHPLC-MS/MS) method measuring edoxaban and its major active metabolite (edoxaban-M4).
Methods: Measurements of edoxaban were performed on patient samples (n=27) with three chromogenic assays (STA®Liquid Anti-Xa, Biophen Heparin LRT® (High and Low) and Biophen DiXaI® (High and Low)) and compared with a validated UHPLC-MS/MS method assessing concentrations of edoxaban and edoxaban-M4. Spearman’s rank correlation coefficient and Bland-Altman plot were used to compare methodologies.
Results: Spearman correlations showed high correlations between chromogenic assays and UHPLC-MS/MS edoxaban measurements (r ranging from 0.94 (Biophen DiXaI®Low) to 0.98 (STA®Liquid Anti-Xa and Biophen Heparin LRT®). Correlations are improved by adding edoxaban-M4 measures to edoxaban. The participation of M6- and M8-metabolite may partly explain this discrepancy. Bland-Altman plots show that chromogenic assays calibrated with edoxaban underestimate edoxaban concentrations when compared with UHPLC-MS/MS measurement. Linear regressions show a tendency to underestimate edoxaban concentrations, especially at higher concentrations (►Figure 1).
Conclusions: Calibrations involving concomitantly edoxaban and active metabolites should be preferred. This will to avoid, especially in case of drug-drug interactions (e.g. P450 cytochrome or transporters inducers), a risk of inadequate control of coagulation, due to different contribution of the metabolites to the total anti-Xa activity which serves for the estimation of edoxaban concentration. Further investigations are needed to evaluate the impact of edoxaban and its active metabolite, edoxaban-M4, on chromogenic assays on a larger sampling.
To cite this abstract in AMA style:Siriez R, Bouvy C, Dogné J-, Hardy M, Hainaut P, Laloy J, Mullier F, Yildiz H, Douxfils J. Comparison of a Validated UHPLC-MS/MS Method and Chromogenic Anti-Xa Assays from Different Manufacturer for the Assessment of Edoxaban and its M4 Metabolite Levels in Plasma [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/comparison-of-a-validated-uhplc-ms-ms-method-and-chromogenic-anti-xa-assays-from-different-manufacturer-for-the-assessment-of-edoxaban-and-its-m4-metabolite-levels-in-plasma/. Accessed September 22, 2023.
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