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The impact of physiological variations on personalized reference intervals and decision limits: an in-depth analysis

  • Abdurrahman Coskun ORCID logo EMAIL logo and Giuseppe Lippi ORCID logo
Published/Copyright: March 11, 2024
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 62 Issue 11

Abstract

The interpretation of laboratory data is a comparative procedure. Physicians typically need reference values to compare patients’ laboratory data for clinical decisions. Therefore, establishing reliable reference data is essential for accurate diagnosis and patient monitoring. Human metabolism is a dynamic process. Various types of systematic and random fluctuations in the concentration/activity of biomolecules are observed in response to internal and external factors. In the human body, several biomolecules are under the influence of physiological rhythms and are therefore subject to ultradian, circadian and infradian fluctuations. In addition, most biomolecules are also characterized by random biological variations, which are referred to as biological fluctuations between subjects and within subjects/individuals. In routine practice, reference intervals based on population data are used, which by nature are not designed to capture physiological rhythms and random biological variations. To ensure safe and appropriate interpretation of patient laboratory data, reference intervals should be personalized and estimated using individual data in accordance with systematic and random variations. In this opinion paper, we outline (i) the main variations that contribute to the generation of personalized reference intervals (prRIs), (ii) the theoretical background of prRIs and (iii) propose new methods on how to harmonize prRIs with the systematic and random variations observed in metabolic activity, based on individuals’ demography.

Keywords: biological variation; circadian rhythm; personalized medicine; reference interval
Corresponding author: Abdurrahman Coskun, Department of Medical Biochemistry, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Kayisdagi cad., No: 32, 34752 Atasehir, Istanbul, Türkiye, Phone: +90 216 5004960, E-mail:

Acknowledgments

The English of some sentences in this manuscript was polished by ChatGPT. A modified version of Figures 1 and 2 were presented in “AACB 60th Annual Scientific Conference” and “Turkish Biochemical Society, 34th National Biochemistry Congress”.

  1. Research ethics: Not applicable.

  2. Informed consent: Not applicable.

  3. Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Competing interests: The authors state no conflict of interest.

  5. Research funding: None declared.

  6. Data availability: Not applicable.

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Received: 2024-01-03
Accepted: 2024-02-27
Published Online: 2024-03-11
Published in Print: 2024-10-28

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2024-0009
Keywords for this article
biological variation; circadian rhythm; personalized medicine; reference interval

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Circulating tumor DNA measurement: a new pillar of medical oncology?
  4. Reviews
  5. Circulating tumor DNA: current implementation issues and future challenges for clinical utility
  6. Circulating tumor DNA methylation: a promising clinical tool for cancer diagnosis and management
  7. Opinion Papers
  8. The final part of the CRESS trilogy – how to evaluate the quality of stability studies
  9. The impact of physiological variations on personalized reference intervals and decision limits: an in-depth analysis
  10. Computational pathology: an evolving concept
  11. Perspectives
  12. Dynamic mirroring: unveiling the role of digital twins, artificial intelligence and synthetic data for personalized medicine in laboratory medicine
  13. General Clinical Chemistry and Laboratory Medicine
  14. Macroprolactin in mothers and their babies: what is its origin?
  15. The influence of undetected hemolysis on POCT potassium results in the emergency department
  16. Quality control in the Netherlands; todays practices and starting points for guidance and future research
  17. QC Constellation: a cutting-edge solution for risk and patient-based quality control in clinical laboratories
  18. OILVEQ: an Italian external quality control scheme for cannabinoids analysis in galenic preparations of cannabis oil
  19. Using Bland-Altman plot-based harmonization algorithm to optimize the harmonization for immunoassays
  20. Comparison of a two-step Tempus600 hub solution single-tube vs. container-based, one-step pneumatic transport system
  21. Evaluating the HYDRASHIFT 2/4 Daratumumab assay: a powerful approach to assess treatment response in multiple myeloma
  22. Insight into the status of plasma renin and aldosterone measurement: findings from 526 clinical laboratories in China
  23. Reference Values and Biological Variations
  24. Reference values for plasma and urine trace elements in a Swiss population-based cohort
  25. Stimulating thyrotropin receptor antibodies in early pregnancy
  26. Within- and between-subject biological variation estimates for the enumeration of lymphocyte deep immunophenotyping and monocyte subsets
  27. Diurnal and day-to-day biological variation of salivary cortisol and cortisone
  28. Web-accessible critical limits and critical values for urgent clinician notification
  29. Cancer Diagnostics
  30. Thyroglobulin measurement is the most powerful outcome predictor in differentiated thyroid cancer: a decision tree analysis in a European multicenter series
  31. Cardiovascular Diseases
  32. Interaction of heparin with human cardiac troponin complex and its influence on the immunodetection of troponins in human blood samples
  33. Diagnostic performance of a point of care high-sensitivity cardiac troponin I assay and single measurement evaluation to rule out and rule in acute coronary syndrome
  34. Corrigendum
  35. Reference intervals of 24 trace elements in blood, plasma and erythrocytes for the Slovenian adult population
  36. Letters to the Editor
  37. Disturbances of calcium, magnesium, and phosphate homeostasis: incidence, probable causes, and outcome
  38. Validation of the enhanced liver fibrosis (ELF)-test in heparinized and EDTA plasma for use in reflex testing algorithms for metabolic dysfunction-associated steatotic liver disease (MASLD)
  39. Detection of urinary foam cells diagnosing the XGP with thrombopenia preoperatively: a case report
  40. Methemoglobinemia after sodium nitrite poisoning: what blood gas analysis tells us (and what it might not)
  41. Novel thiopurine S-methyltransferase (TPMT) variant identified in Malay individuals
  42. Congress Abstracts
  43. 56th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC – Laboratory Medicine)
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