Laboratory testing for activated protein C resistance: rivaroxaban induced interference and a comparative evaluation of andexanet alfa and DOAC Stop to neutralise interference
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,
Abstract
Background
Investigation of hemostasis is problematic when patients are on anticoagulant therapy. Rivaroxaban especially causes substantial interference, extending many clot-based tests, thereby leading to false positive or negative events. In particular, rivaroxaban affects some assays for activated protein C resistance (APCR).
Methods
We assessed, in an international setting, cross laboratory (n = 31) testing using four samples to evaluate rivaroxaban induced interference in APCR testing, and whether this interference could be neutralised. The samples comprised: (A) pool of normal plasma (APCR-negative control); (B) this normal pool spiked with rivaroxaban (200 ng/mL) to create rivaroxaban-induced interference (potential ‘false’ positive APCR event sample); (C) the rivaroxaban sample subsequently treated with a commercial direct oral anticoagulant ‘DOAC-neutraliser’ (DOAC Stop), or (D) treated with andexanet alfa (200 μg/mL). Testing was performed blind to sample type.
Results
The rivaroxaban-spiked sample generated false positive APCR results for some, but unexpectedly not most APCR-tests. The sample treated with DOAC Stop evidenced a correction in the rivaroxaban-affected APCR assays, and did not otherwise adversely affect the rivaroxaban ‘unaffected’ APCR assays. The andexanet alfa-treated sample did not evidence correction of the false positive APCR, and instead unexpectedly exacerbated false positive APCR status with many tests.
Conclusions
DOAC Stop was able to neutralise any APCR interference induced by rivaroxaban. In contrast, andexanet alfa did not negate such interference, and instead unexpectedly created more false-positive APCR events.
Acknowledgements
We thank the ICPMR technical staff for performance of some preliminary laboratory testing. The RCPAQAP staff are thanked for logistical support in packing and dispatching study material, and Nalishia Munuswamy is acknowledged for help in designing the results form. We also thank all study participants. Portola Pharmaceuticals Inc (San Francisco, CA, USA) is acknowledged for suppling andexanet alfa, and Haematex (Sydney, Australia) provided DOAC Stop as used in this exercise. Neither Portola nor Haematex had any influence in reported study findings, which remain the sole responsibility of the authors. New South Wales (NSW) Health Pathology is acknowledged for providing in-kind support to permit study completion. The views expressed in this paper are those of the authors, and are not necessarily those of NSW Health Pathology.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: Ross Baker declares the following: Industry led Clinical Trial Support payment to Institution: Bayer, Shire, Pfizer, Daiichi Sankyo, and CSL Behring, Roche, Amgen, Celgene, Rigel Pharmaceuticals, Abbvie, Sanofi, MorphoSys AG, Acerta Pharma, Jansen-Cileg. Clinical Advisory boards: Roche. Conference Travel and speaker support: Shire, Roche, CSL Behring, Bayer, BMS, Novo Nordisk. Research support from: Shire, Bayer, Bristol- Myers Squibb, Boehringer Ingelheim, Portola, Technoclone. The remaining authors stated that they had no interests which might be perceived as posing a conflict or bias.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2019-1160).
©2020 Walter de Gruyter GmbH, Berlin/Boston
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- Editorial
- Quality controls for serology: an unfinished agenda
- A modern and pragmatic definition of Laboratory Medicine
- Reviews
- Blood biochemical characteristics of patients with coronavirus disease 2019 (COVID-19): a systemic review and meta-analysis
- ISO/TS 20914:2019 – a critical commentary
- Mini Review
- Reporting of D-dimer data in COVID-19: some confusion and potential for misinformation
- Opinion Paper
- Implementation of metrological traceability in laboratory medicine: where we are and what is missing
- IFCC Recommendation
- Recommendation for performance verification of patient-based real-time quality control
- Genetics and Molecular Diagnostics
- Comparison of BCR-ABL1 quantification in peripheral blood and bone marrow using an International Scale-standardized assay for assessment of deep molecular response in chronic myeloid leukemia
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- Risk assessment of the total testing process based on quality indicators with the Sigma metrics
- Determination of hemolysis cut-offs for biochemical and immunochemical analytes according to their value
- A computer model for professional competence assessment according to ISO 15189
- Traceability validation of six enzyme measurements on the Abbott Alinity c analytical system
- Evaluating the need for free glycerol blanking for serum triglyceride measurements at Charlotte Maxeke Johannesburg Academic Hospital
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- Changes in the result of antinuclear antibody immunofluorescence assay on HEp-2 cells reflect disease activity status in systemic lupus erythematosus
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