Measuring residual anti‐Xa activity of direct factor Xa inhibitors after reversal with andexanet alfa

作者：Matthieu Bourdin, Delphine Perrotin, Olivier Mathieu, Tristan Herve, François Depasse, Genmin Lu, Pamela B. Conley, G. Contant · 发表于：International Journal of Laboratory Hematology · 年份：2021 · DOI：10.1111/ijlh.13591 · 被引用次数：21 · 研究领域：Atrial Fibrillation Management and Outcomes、Acute Kidney Injury Research、Acute Myocardial Infarction Research

INTRODUCTION: Andexanet alfa (AnXa) was developed for anticoagulant effect reversal of direct factor Xa inhibitors (DXaI) (apixaban, rivaroxaban, edoxaban) in emergency situations. Regular anti-Xa assays are not suitable to evaluate anti-Xa activity after AnXa administration because of the high sample dilution resulting in the AnXa-DXaI dissociation which gives inaccurately high DXaI measured concentrations. This study aimed at developing dedicated STA-Liquid anti-Xa test set-ups for accurately measuring DXaI after reversal with AnXa. METHODS: Modified anti-Xa test set-ups, with reduced sample dilution, were developed to overcome regular assays limitations and to improve measured accuracy with results comparable to Portola microplate reference method used in clinical studies. Both regular and optimized assays were used to measure DXaI concentration in AnXa-containing samples. Quality controls, normal pooled plasma spiked with five DXaI and three AnXa concentrations, samples from DXaI-treated patients spiked with AnXa and ex vivo healthy volunteers having received both DXaI and AnXa were used. RESULTS: The lower limit of quantitation of optimized anti-Xa assays was <10 ng/mL with CVs ≤10%. DXaI samples containing 300 ng/mL and 1 µmol/L AnXa resulted in DXaI residual concentrations of 29-72 ng/mL depending on the DXaI (76%-90% reversal), compared to 20-28 ng/mL with reference method (92%-94% reversal) and 135-165 ng/mL with regular assays (about 50% reversal). CONCLUSION: Modif...