Home Medicine DOAC-Remove abolishes the effect of direct oral anticoagulants on activated protein C resistance testing in real-life venous thromboembolism patients
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DOAC-Remove abolishes the effect of direct oral anticoagulants on activated protein C resistance testing in real-life venous thromboembolism patients

  • Magdalena Kopytek , Michał Ząbczyk ORCID logo , Krzysztof P. Malinowski , Anetta Undas and Joanna Natorska EMAIL logo
Published/Copyright: September 4, 2019
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 58 Issue 3

Abstract

Background

Direct oral anticoagulants (DOACs) may cause false results of activated protein C resistance (APC-R) ratio. DOAC-Remove, a new reagent based on activated carbon, has been designed to eliminate the interference of DOACs on coagulation assays. The aim of the study was to investigate whether the use of DOAC-Remove enables to determine APC-R in patients treated with DOACs.

Methods

We assessed 74 venous thromboembolism (VTE) patients, including 25 on rivaroxaban, 25 on apixaban and 24 taking dabigatran. APC-R was determined using the Russell Viper Venom Time (RVVT)-based clotting test. APC-R and DOAC concentrations were tested at baseline and following DOAC-Remove. Thrombophilia, including factor V Leiden (FVL) mutation was tested.

Results

FVL mutation was found in 20 (27%) patients. The APC-R ratio at baseline was measurable in 43 patients (58.1%), including 20 (80%) on rivaroxaban, 19 (76%) on apixaban and four (16.7%) on dabigatran. In patients with measurable APC-R at baseline, the ratio >2.9 was found in 23 patients (53.5%). In 16 (37.2%) subjects APC-R ratio <1.8 suggested FVL mutation which was genetically confirmed. Four (9.3%) FVL carriers on dabigatran showed negative/equivocal APC-R results. In 11 (14.9%) patients taking rivaroxaban or apixaban, in whom blood was collected 2–5 h since the last dose, we observed unmeasurable APC-R. DOAC-Remove almost completely eliminated all plasma DOACs. After addition of DOAC-Remove all APC-R ratios were measurable. In four FVL carriers on dabigatran with false negative APC-R, DOAC-Remove resulted in APC-R ratios <1.8.

Conclusions

DOAC-Remove effectively reduces DOACs concentration in plasma, which enables FVL testing using APC-R.

Keywords: activated protein C resistance (APC-R); direct oral anticoagulants (DOACs); DOAC-Remove; factor V Leiden mutation (FVL); venous thromboembolism (VTE)
Corresponding author: Joanna Natorska, PhD, John Paul II Hospital, Kraków, Poland; and Institute of Cardiology, Jagiellonian University School of Medicine, 80 Pradnicka St, 31-202 Kraków, Poland, Phone: +48 12 614 30 04, Fax: +48 12 614 21 20

Funding source: Jagiellonian University Medical College

Award Identifier / Grant number: N41/DBS/ 000184

Funding statement: This work was supported by a grant from the Jagiellonian University Medical College (N41/DBS/ 000184, Funder Id: http://dx.doi.org/10.13039/100009045 to A.U.).

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Employment or leadership: None declared.

  3. Honorarium: None declared.

  4. 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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Received: 2019-06-27
Accepted: 2019-08-15
Published Online: 2019-09-04
Published in Print: 2020-02-25

©2020 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2019-0650
Keywords for this article
activated protein C resistance (APC-R); direct oral anticoagulants (DOACs); DOAC-Remove; factor V Leiden mutation (FVL); venous thromboembolism (VTE)

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Progress in understanding the use of human chorionic gonadotropin as a tumor marker
  4. Reviews
  5. Biomarkers for prostate cancer: prostate-specific antigen and beyond
  6. Gut microbiome investigation in celiac disease: from methods to its pathogenetic role
  7. Opinion Papers
  8. Understanding and managing interferences in clinical laboratory assays: the role of laboratory professionals
  9. A step forward in identifying the right human chorionic gonadotropin assay for testicular cancer
  10. EFLM Opinion Paper
  11. Validation and verification of examination procedures in medical laboratories: opinion of the EFLM Working Group Accreditation and ISO/CEN standards (WG-A/ISO) on dealing with ISO 15189:2012 demands for method verification and validation
  12. Guidelines and Recommendations
  13. An updated protocol based on CLSI document C37 for preparation of off-the-clot serum from individual units for use alone or to prepare commutable pooled serum reference materials
  14. General Clinical Chemistry and Laboratory Medicine
  15. Highly accurate and explainable detection of specimen mix-up using a machine learning model
  16. Impact of delta check time intervals on error detection capability
  17. Effect of long-term frozen storage and thawing of stool samples on faecal haemoglobin concentration and diagnostic performance of faecal immunochemical tests
  18. A more accurate prediction to rule in and rule out pre-eclampsia using the sFlt-1/PlGF ratio and NT-proBNP as biomarkers
  19. Macro vitamin B12: an underestimated threat
  20. Evaluation of the primary biliary cholangitis-related serologic profile in a large cohort of Belgian systemic sclerosis patients
  21. High frequency of anti-parietal cell antibody (APCA) and intrinsic factor blocking antibody (IFBA) in individuals with severe vitamin B12 deficiency – an observational study in primary care patients
  22. DOAC-Remove abolishes the effect of direct oral anticoagulants on activated protein C resistance testing in real-life venous thromboembolism patients
  23. Cancer Diagnostics
  24. How comparable are total human chorionic gonadotropin (hCGt) tumour markers assays?
  25. Diabetes
  26. Measurement accuracy of two professional-use systems for point-of-care testing of blood glucose
  27. Letters to the Editor
  28. Human chorionic gonadotropin in oncology: a matter of tight (bio)marking
  29. More robust analytical evidence should support the selection of human chorionic gonadotropin assays for oncology application
  30. Letter in reply to the letter to the editor of Ferraro S and Panteghini M with the title “More robust analytical evidence should support the selection for human chorionic gonadotropin assays for oncology application”
  31. Definition of analytical quality specifications for serum total folate measurements using a simulation outcome-based model
  32. Alarmed by misleading interference in free T3 and free T4 assays: a new case of anti-streptavidin antibodies
  33. A root cause analysis of ‘falsely elevated’ oxygen saturation: investigation of pneumatic tube transport and differences between estimated and measured saturation in a critical patient population
  34. The chaos of serologic markers in interstitial pneumonia with autoimmune features can be corrected by the laboratory physician
  35. Vitamin A and E gender and age stratification in adults
  36. Detection of monoclonal B-lymphocytosis: interest of cellular population data and CytoDiff™ analysis
  37. Urinary reference intervals for gadolinium in individuals without recent exposure to gadolinium-based contrast agents
  38. Molecular diagnosis of toxoplasmosis: evaluation of automated DNA extraction using eMAG® (bioMérieux) on buffy coat, cerebrospinal and bronchoalveolar lavage fluids
  39. Retraction
  40. Retraction of: The Effect of a Gender Difference in the Apolipoprotein E Gene DNA Polymorphism on Serum Lipid Levels in a Serbian Healthy Population
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