Journal Information
Journal ID (publisher-id): BM
Journal ID (nlm-ta): Biochem Med (Zagreb)
Title: Biochemia Medica
Abbreviated Title: Biochem. Med. (Zagreb)
ISSN (print): 1330-0962
ISSN (electronic): 1846-7482
Publisher: Croatian Society of Medical Biochemistry and Laboratory Medicine
Article Information
Copyright statement: ©Croatian Society of Medical Biochemistry and Laboratory Medicine.
Copyright: 2019, Croatian Society of Medical Biochemistry
License (open-access):
This is an Open Access article distributed under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Date received: 28 February 2019
Date accepted: 15 September 2019
Publication date (electronic): 15 December 2019
Publication date (print): 15 February 2020
Volume: 30
Issue: 1
Electronic Location Identifier: 010702
Publisher ID: bm-30-1-010702
DOI: 10.11613/BM.2020.010702
Chromogenic anti-FXa assay calibrated with low molecular weight heparin in patients treated with rivaroxaban and apixaban: possibilities and limitations
Ivana Ćelap[1]
Diana Delić Brkljačić[2]
Nikola Pavlović[2]
Sandra Šupraha Goreta[3]
Ivana Kobasić[4]
Arijana Lovrenčić-Huzjan[4]
Vanja Bašić Kes[4]
[1] Department of Clinical Chemistry, Sestre milosrdnice University Hospital Center, Zagreb, Croatia
[2] Department of Cardiovascular Diseases, Sestre milosrdnice University Hospital Center, Zagreb, Croatia
[3] Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Croatia
[4] Department of Neurology, Sestre milosrdnice University Hospital Center, Zagreb, Croatia
Author notes:
[*] Corresponding author: margeticsandra@gmail.com
Introduction
Clinical application of rivaroxaban and apixaban does not require therapeutic monitoring. Commercial anti-activated factor X (anti-FXa) inhibition methods for all anti-FXa drugs are based on the same principle, so there are attempts to evaluate potential clinical application of heparin-calibrated anti-FXa assay as an alternative method for direct FXa inhibitors. We aimed to evaluate relationship between anti-FXa methods calibrated with low molecular weight heparin (LMWH) and with drug specific calibrators, and to determine whether commercial LMWH anti-FXa assay can be used to exclude the presence of clinically relevant concentrations of rivaroxaban and apixaban.
Materials and methods
Low molecular weight heparin calibrated reagent (Siemens Healthineers, Marburg, Germany) was used for anti-FXa activity measurement. Innovance heparin (Siemens Healthineers, Marburg, Germany) calibrated with rivaroxaban and apixaban calibrators (Hyphen BioMed, Neuville-sur-Oise, France) was used for quantitative determination of FXa inhibitors.
Results
Analysis showed good agreement between LMWH calibrated and rivaroxaban calibrated activity (κ = 0.76) and very good agreement with apixaban calibrated anti-Xa activity (κ = 0.82), respectively. Low molecular weight heparin anti-FXa activity cut-off values of 0.05 IU/mL and 0.1 IU/mL are suitable for excluding the presence of clinically relevant concentrations (< 30 ng/mL) of rivaroxaban and apixaban, respectively. Concentrations above 300 ng/mL exceeded upper measurement range for LMWH anti-FXa assay and cannot be determined by this method.
Conclusion
Low molecular weight heparin anti-FXa assay can be used in emergency clinical conditions for ruling out the presence of clinically relevant concentrations of rivaroxaban and apixaban. However, use of LMWH anti-FXa assay is not appropriate for their quantitative determination as an interchangeable method.
Keywords: apixaban; DOAC; factor Xa inhibitors; LMWH; rivaroxaban
