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

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 samp...

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Autores principales: Bourdin, Matthieu, Perrotin, Delphine, Mathieu, Olivier, Herve, Tristan, Depasse, François, Lu, Genmin, Conley, Pamela B., Contant, Geneviève
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453859/
https://www.ncbi.nlm.nih.gov/pubmed/34092030
http://dx.doi.org/10.1111/ijlh.13591
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author Bourdin, Matthieu
Perrotin, Delphine
Mathieu, Olivier
Herve, Tristan
Depasse, François
Lu, Genmin
Conley, Pamela B.
Contant, Geneviève
author_facet Bourdin, Matthieu
Perrotin, Delphine
Mathieu, Olivier
Herve, Tristan
Depasse, François
Lu, Genmin
Conley, Pamela B.
Contant, Geneviève
author_sort Bourdin, Matthieu
collection PubMed
description 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: Modified test set‐ups are automated alternative to reference method with improved precision and reproducibility. They can be run in all laboratories where regular anti‐Xa assays are performed using commercially available reagents.
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spelling pubmed-84538592021-09-27 Measuring residual anti‐Xa activity of direct factor Xa inhibitors after reversal with andexanet alfa Bourdin, Matthieu Perrotin, Delphine Mathieu, Olivier Herve, Tristan Depasse, François Lu, Genmin Conley, Pamela B. Contant, Geneviève Int J Lab Hematol ORIGINAL ARTICLES 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: Modified test set‐ups are automated alternative to reference method with improved precision and reproducibility. They can be run in all laboratories where regular anti‐Xa assays are performed using commercially available reagents. John Wiley and Sons Inc. 2021-06-05 2021-08 /pmc/articles/PMC8453859/ /pubmed/34092030 http://dx.doi.org/10.1111/ijlh.13591 Text en © 2021 The Authors. International Journal of Laboratory Hematology published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle ORIGINAL ARTICLES
Bourdin, Matthieu
Perrotin, Delphine
Mathieu, Olivier
Herve, Tristan
Depasse, François
Lu, Genmin
Conley, Pamela B.
Contant, Geneviève
Measuring residual anti‐Xa activity of direct factor Xa inhibitors after reversal with andexanet alfa
title Measuring residual anti‐Xa activity of direct factor Xa inhibitors after reversal with andexanet alfa
title_full Measuring residual anti‐Xa activity of direct factor Xa inhibitors after reversal with andexanet alfa
title_fullStr Measuring residual anti‐Xa activity of direct factor Xa inhibitors after reversal with andexanet alfa
title_full_unstemmed Measuring residual anti‐Xa activity of direct factor Xa inhibitors after reversal with andexanet alfa
title_short Measuring residual anti‐Xa activity of direct factor Xa inhibitors after reversal with andexanet alfa
title_sort measuring residual anti‐xa activity of direct factor xa inhibitors after reversal with andexanet alfa
topic ORIGINAL ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453859/
https://www.ncbi.nlm.nih.gov/pubmed/34092030
http://dx.doi.org/10.1111/ijlh.13591
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