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High incidence of macrotroponin I with a high-sensitivity troponin I assay

  • Janet V. Warner EMAIL logo and George A. Marshall
Published/Copyright: April 19, 2016
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 54 Issue 11

Abstract

Background:

Cardiac troponin is the preferred biomarker of myocardial injury. High-sensitivity troponin assays allow measurement of very low levels of troponin with excellent precision. After the introduction of a high-sensitivity troponin I assay the laboratory began to receive enquiries from clinicians about clinically discordant elevated troponin I results. This led to a systematic investigation and characterisation of the cause.

Methods:

Routine clinical samples were measured by the Architect High Sensitive Troponin-I (hsTnI) and the VITROS Troponin I ES assays (VitrosTnI). Results that were elevated according to the Architect but not the VITROS assay (Group 1) or results elevated by both assays but disproportionately higher on the Architect (Group 2) were re-analysed for hsTnI after re-centrifugation, multiple dilutions, incubation with heterophilic blocking reagents, polyethylene glycol (PEG) precipitation, and Protein A/G/L treatment. Sephacryl S-300 HR gel filtration chromatography (GFC) was performed on selected specimens.

Results:

A high molecular weight complex containing immunoreactive troponin I and immunoglobulin (macrotroponin I) was identified in 5% of patients with elevated hsTnI. Patients with both macrotroponin and myocardial injury had higher and longer elevation of hsTnI compared with VitrosTnI with peaks of both macrotroponin and free troponin I-C complex on GFC.

Conclusions:

Circulating macrotroponin I (macroTnI) causes elevated hsTnI results with the Architect High Sensitive Troponin-I assay with the potential to be clinically misleading. The assay involved in this investigation may not be the only assay affected by macrotroponin. It is important for laboratories and clinicians to be aware of and develop processes to identify and manage specimens with elevated results due to macrotroponin.

Keywords: false-positive troponin; high-sensitivity assay; macrotroponin; macrotroponin I

Acknowledgments:

The authors would like to thank the scientific staff of Mater Pathology for patiently PEG-ing, diluting, setting up Scantibodies tubes, and analysing multiple column fractions.

  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 organisation(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: 2015-12-29
Accepted: 2016-3-16
Published Online: 2016-4-19
Published in Print: 2016-11-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2015-1276
Keywords for this article
false-positive troponin; high-sensitivity assay; macrotroponin; macrotroponin I

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. CCLM Award for the Most Cited Paper Recently Published
  4. Laboratory economics. Risk or opportunity?
  5. Reviews
  6. Molecular diagnosis and precision medicine in allergy management
  7. The insulin autoimmune syndrome (IAS) as a cause of hypoglycaemia: an update on the pathophysiology, biochemical investigations and diagnosis
  8. Opinion Paper
  9. Role of microsatellite instability, immunohistochemistry and mismatch repair germline aberrations in immunosuppressed transplant patients: a phenocopy dilemma in Muir-Torre syndrome
  10. Genetics and Molecular Diagnostics
  11. Time and tumor type (primary or metastatic) do not influence the detection of BRAF/NRAS mutations in formalin fixed paraffin embedded samples from melanomas
  12. False low holotranscobalamin levels in a patient with a novel TCN2 mutation
  13. General Clinical Chemistry and Laboratory Medicine
  14. Quality performance of laboratory testing in pharmacies: a collaborative evaluation
  15. Cost evaluation of clinical laboratory in Taiwan’s National Health System by using activity-based costing
  16. Impact of sample processing on the measurement of circulating microparticles: storage and centrifugation parameters
  17. HbA1c: EQA in Germany, Belgium and the Netherlands using fresh whole blood samples with target values assigned with the IFCC reference system
  18. Iohexol clearance in unstable critically ill patients: a tool to assess glomerular filtration rate
  19. Characteristics of Chinese patients with antiphospholipid syndrome and the ability of lupus anticoagulant assays to identify them
  20. Reference Values and Biological Variations
  21. Distribution of soluble suppression of tumorigenicity 2 (sST2), N-terminal pro-brain natriuretic peptide (NT-proBNP), high sensitive troponin I and high-sensitive troponin T in umbilical cord blood
  22. Hematology and Coagulation
  23. Evaluation of Mindray BC-6800 body fluid mode for automated cerebrospinal fluid cell counting
  24. Cancer Diagnostics
  25. Increased sialylation and reduced fucosylation of exfoliated cervical cells are potential markers of carcinogenesis in the cervix
  26. Cardiovascular Diseases
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