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CC BY 4.0 · TH Open 2022; 06(03): e238-e247
DOI: 10.1055/s-0042-1751072
Original Article

Rapid Detection of Apixaban by a ROTEM-Based Approach and Reversibility with Andexanet Alfa or DOAC-Stop

Viktor Taune
1   Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Karolinska Institutet, Stockholm, Sweden
,
Mika Skeppholm
1   Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Karolinska Institutet, Stockholm, Sweden
,
Anna Ågren
1   Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Karolinska Institutet, Stockholm, Sweden
,
Agneta Wikman
2   Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska University Hospital, Stockholm, Sweden; Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
,
Andreas Hillarp
3   Department of Translational Medicine, Clinical Chemistry Malmö, Lund University, Malmö, Sweden
4   Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway
,
Håkan Wallén
1   Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Karolinska Institutet, Stockholm, Sweden
› Author Affiliations Funding The study was supported by grants from the Swedish Heart-Lung foundation, the Stockholm County Council (ALF project), the Swedish Society of Medicine, and Stiftelsen Hjärtat. Andexanet alfa for experimental use was kindly supplied by Alexion AstraZeneca Rare Disease (USA).
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Abstract

Background A rapid test to detect apixaban treatment would be useful in acute situations such as major bleeding, urgent surgery, or in acute thrombosis.

Objective This article aims to study if the viscoelastic test rotational thromboelastometry (ROTEM) can rapidly detect apixaban in whole blood using modified triggers based on factor Xa (FXa) or Russell viper venom (RVV).

Method ROTEM clotting time (CT) was measured in samples from 40 patients on apixaban treatment, and in vitro in samples spiked with apixaban (20–500 ng/mL). Commercially available trigger Ex-tem was compared with modified triggers based on FXa or RVV. Reversibility of apixaban in the samples was studied; CT was measured with and without addition of DOAC-Stop or andexanet alfa, respectively, and the difference in CT was calculated (CTdiff).

Results Using FXa as trigger, we detected apixaban concentrations at 20 ng/mL and above with 100% sensitivity and 100% specificity in patient samples and in vitro. Corresponding data for Ex-tem were 92% sensitivity and 100% specificity in patients, and 94% sensitivity and 100% specificity in vitro, and for RVV 97% sensitivity and 94% specificity in patients, and 97% sensitivity and 100% specificity in vitro, respectively. CTdiff data were similar. Patient sample data were obtained within 20 minutes from sampling.

Conclusion Apixaban at low therapeutic concentrations was detected within 20 minutes, and with high sensitivity and specificity. A trigger based on FXa outperformed the commercial trigger Ex-tem and a trigger based on RVV. ROTEM with a FXa-based trigger is a promising method to detect apixaban bedside in acute settings.

Keywords

atrial fibrillation - apixaban - drug monitoring - point-of-care test - thromboelastometry

Authors' Contributions

V.T, M.S., A.Å., A.W., and H.W. designed and planned the experiments. V.T. recruited patients and healthy volunteers and performed the experiments. V.T., M.S., A.Å., A.W., A.H., and H.W. analyzed and interpreted the results and contributed to writing the manuscript.


Supplementary Material



Publication History

Received: 12 March 2022

Accepted: 09 May 2022

Article published online:
29 August 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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