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Real life dabigatran and metabolite concentrations, focused on inter-patient variability and assay differences in patients with atrial fibrillation

  • Kristel Boonen , Ellen Schmitz , Fleur Rozestraten , Dennis van den Heuvel , Luc Brunsveld , Pepijn van der Voort and Daan van de Kerkhof EMAIL logo
Published/Copyright: March 22, 2017
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 55 Issue 12

Abstract

Background:

Dabigatran is prescribed to increasing numbers of patients with atrial fibrillation (AF). Although routine monitoring is not considered to be useful, measuring drug concentrations can be clinically relevant in specific situations. The aim of this study was the comparison of different functional and non-functional assays for determination of dabigatran concentrations at different timepoints in a real-life patient population with AF. We focused on the differences between assays in identifying patients with low drug concentrations. Furthermore, we studied the effect of glucuronidation on the established concentration as determined with different assays.

Methods:

This study established dabigatran concentration ranges in 40 real-life AF patients by an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) reference method and compared these with results from coagulation assays (Hemoclot dTT, LD-dTT and ECA). Samples were taken just before and 2 and 4 h after taking the drug.

Results:

A wide range of concentrations at different time points was found in this patient group. Coagulation assays correlate best with UPLC-MS/MS results that include the glucuronidated metabolites, showing that the pharmacologically active glucuronides are also measured in coagulation testing. The LD-dTT has the best agreement with UPLC-MS/MS and combines good sensitivity with high specificity. Several patients show consistently low or high drug concentrations, implying that drug exposure differs between patients.

Conclusions:

Based on the association of dabigatran concentrations with bleeding and thromboembolic risk, we believe that dabigatran monitoring could be beneficial for further optimizing anticoagulation therapy in AF.

Keywords: atrial fibrillation; blood coagulation test; dabigatran; hemorrhage; thromboembolism

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

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. 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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Supplemental Material:

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2016-0681).

Received: 2016-8-1
Accepted: 2017-2-6
Published Online: 2017-3-22
Published in Print: 2017-10-26

©2017 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2016-0681
Keywords for this article
atrial fibrillation; blood coagulation test; dabigatran; hemorrhage; thromboembolism

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Tumor microenvironment and systemic disease: a dual target in medical oncology (also in the case of biomarkers)
  4. Reviews
  5. Sample types applied for molecular diagnosis of therapeutic management of advanced non-small cell lung cancer in the precision medicine
  6. The impact of pneumatic tube system on routine laboratory parameters: a systematic review and meta-analysis
  7. Opinion Paper
  8. How to reduce scientific irreproducibility: the 5-year reflection
  9. EFLM Paper
  10. Strategies to define performance specifications in laboratory medicine: 3 years on from the Milan Strategic Conference
  11. General Clinical Chemistry and Laboratory Medicine
  12. Intensive educational efforts combined with external quality assessment improve the preanalytical phase in general practitioner offices and nursing homes
  13. Separate patient serum sodium medians from males and females provide independent information on analytical bias
  14. Are admission procalcitonin levels universal mortality predictors across different medical emergency patient populations? Results from the multi-national, prospective, observational TRIAGE study
  15. Biochemical testing in a laboratory tent and semi-intensive care of Ebola patients on-site in a remote part of Guinea: a paradigm shift based on a bleach-sensitive point-of-care device
  16. Efficient reporting of the estimated glomerular filtration rate without height in pediatric patients with cancer
  17. Evaluation of thyroid test utilization through analysis of population-level data
  18. Relation of serum γ-glutamyl transferase activity with copper in an adult population
  19. Impact of a single oral dose of 100,000 IU vitamin D3 on profiles of serum 25(OH)D3 and its metabolites 24,25(OH)2D3, 3-epi-25(OH)D3, and 1,25(OH)2D3 in adults with vitamin D insufficiency
  20. Automated antinuclear immunofluorescence antibody analysis is a reliable approach in routine clinical laboratories
  21. Infrared analyzers for breast milk analysis: fat levels can influence the accuracy of protein measurements
  22. Hematology and Coagulation
  23. A new approach to define acceptance limits for hematology in external quality assessment schemes
  24. The effects of transport by car on coagulation tests
  25. Combined measurement of factor XIII and D-dimer is helpful for differential diagnosis in patients with suspected pulmonary embolism
  26. Reference Values and Biological Variations
  27. Influence of age, gender and body mass index on late-night salivary cortisol in healthy adults
  28. Cancer Diagnostics
  29. Assessment of real-time PCR method for detection of EGFR mutation using both supernatant and cell pellet of malignant pleural effusion samples from non-small-cell lung cancer patients
  30. Detection of EGFR mutations in patients with non-small cell lung cancer by high resolution melting. Comparison with other methods
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