Within-day biological variation and hour-to-hour reference change values for hematological parameters
-
Judith M. Hilderink
, Lieke J.J. Klinkenberg , Kristin M. Aakre , Norbert C.J. de Wit , Yvonne M.C. Henskens , Noreen van der Linden , Otto Bekers , Roger J.M.W. Rennenberg , Richard P. Koopmans and Steven J.R. Meex
Abstract
Background:
Middle- and long-term biological variation data for hematological parameters have been reported in the literature. Within-day 24-h variability profiles for hematological parameters are currently lacking. However, comprehensive hour-to-hour variability data are critical to detect diurnal cyclical rhythms, and to take into account the ‘time of sample collection’ as a possible determinant of natural fluctuation. In this study, we assessed 24-h variation profiles for 20 hematological parameters.
Methods:
Blood samples were collected under standardized conditions from 24 subjects every hour for 24 h. At each measurement, 20 hematological parameters were determined in duplicate. Analytical variation (CVA), within-subject biological variation (CVI), between-subject biological variation (CVG), index of individuality (II), and reference change values (RCVs) were calculated. For the parameters with a diurnal rhythm, hour-to-hour RCVs were determined.
Results:
All parameters showed higher CVG than CVI. Highest CVG was found for eosinophils (46.6%; 95% CI, 34.9%–70.1%) and the lowest value was mean corpuscular hemoglobin concentration (MCHC) (3.2%; 95% CI, 2.4%–4.8%). CVI varied from 0.4% (95% CI, 0.32%–0.42%) to 20.9% (95% CI, 19.4%–22.6%) for red cell distribution width (RDW) and eosinophils, respectively. Six hematological parameters showed a diurnal rhythm.
Conclusions:
We present complete 24-h variability profiles for 20 hematological parameters. Hour-to-hour reference changes values may help to better discriminate between random fluctuations and true changes in parameters with rhythmic diurnal oscillations.
Acknowledgments
The skillful technical assistance of the laboratory research analyst V. W. Kleijnen is gratefully acknowledged.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This study was supported by an Academic Incentive Grant from Maastricht University Medical Center to S.J.R.M.
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.
References
1. Fraser CG. Reference change values. Clin Chem Lab Med 2012;50:807–12.10.1515/cclm.2011.733Search in Google Scholar PubMed
2. Bailey D, Bevilacqua V, Colantonio DA, Pasic MD, Perumal N, Chan MK, et al. Pediatric within-day biological variation and quality specifications for 38 biochemical markers in the caliper cohort. Clin Chem 2014;60:518–29.10.1373/clinchem.2013.214312Search in Google Scholar PubMed
3. Nunes LA, Brenzikofer R, de Macedo DV. Reference change values of blood analytes from physically active subjects. Eur J Appl Physiol 2010;110:191–8.10.1007/s00421-010-1493-8Search in Google Scholar PubMed
4. Maes M, Scharpe S, Cooreman W, Wauters A, Neels H, Verkerk R, et al. Components of biological, including seasonal, variation in hematological measurements and plasma fibrinogen concentrations in normal humans. Experientia 1995;51:141–9.10.1007/BF01929358Search in Google Scholar PubMed
5. Dot D, Miro J, Fuentes-Arderiu X. Within-subject biological variation of hematological quantities and analytical goals. Arch Pathol Lab Med 1992;116:825–6.Search in Google Scholar
6. Pineda-Tenor D, Laserna-Mendieta EJ, Timon-Zapata J, Rodelgo-Jimenez L, Ramos-Corral R, Recio-Montealegre A, et al. Biological variation and reference change values of common clinical chemistry and haematologic laboratory analytes in the elderly population. Clin Chem Lab Med 2013;51:851–62.10.1515/cclm-2012-0701Search in Google Scholar PubMed
7. Rudez G, Meijer P, Spronk HM, Leebeek FW, ten Cate H, Kluft C, et al. Biological variation in inflammatory and hemostatic markers. J Thromb Haemost 2009;7:1247–55.10.1111/j.1538-7836.2009.03488.xSearch in Google Scholar PubMed
8. Statland BE, Winkel P, Harris SC, Burdsall MJ, Saunders AM. Evaluation of biologic sources of variation of leukocyte counts and other hematologic quantities using very precise automated analyzers. Am J Clin Pathol 1978;69:48–54.10.1093/ajcp/69.1.48Search in Google Scholar PubMed
9. Yang D, Zhou Y, Yang C. Daytime biological variation of hematological parameters in a healthy chinese population. Int J Lab Hematol 2016 [Epub ahead of print].10.1111/ijlh.12569Search in Google Scholar PubMed
10. Sennels HP, Jorgensen HL, Hansen AL, Goetze JP, Fahrenkrug J. Diurnal variation of hematology parameters in healthy young males: the bispebjerg study of diurnal variations. Scand J Clin Lab Invest 2011;71:532–41.10.3109/00365513.2011.602422Search in Google Scholar PubMed
11. Zhang P, Tang H, Chen K, Chen Y, Xu D. Biological variations of hematologic parameters determined by unicel dxh 800 hematology analyzer. Arch Pathol Lab Med 2013;137:1106–10.10.5858/arpa.2012-0377-OASearch in Google Scholar PubMed
12. Harris EK. Statistical aspects of reference values in clinical pathology. Prog Clin Pathol 1981;8:45–66.Search in Google Scholar
13. Bartlett WA, Braga F, Carobene A, Coskun A, Prusa R, Fernandez-Calle P, et al. A checklist for critical appraisal of studies of biological variation. Clin Chem Lab Med 2015;53:879–85.10.1515/cclm-2014-1127Search in Google Scholar PubMed
14. Klinkenberg LJ, Wildi K, van der Linden N, Kouw IW, Niens M, Twerenbold R, et al. Diurnal rhythm of cardiac troponin: consequences for the diagnosis of acute myocardial infarction. Clin Chem 2016;62:1602–11.10.1373/clinchem.2016.257485Search in Google Scholar PubMed
15. American Diabetes A. Diagnosis and classification of diabetes mellitus. Diabetes Care 2004;27(Suppl 1):S5–10.10.2337/diacare.27.2007.S5Search in Google Scholar
16. Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T, et al. Estimating glomerular filtration rate from serum creatinine and cystatin c. N Engl J Med 2012;367:20–9.10.1056/NEJMoa1114248Search in Google Scholar PubMed PubMed Central
17. Burnett RW. Accurate estimation of standard deviations for quantitative methods used in clinical chemistry. Clin Chem 1975;21:1935–8.10.1093/clinchem/21.13.1935Search in Google Scholar
18. Fraser CG, Harris EK. Generation and application of data on biological variation in clinical chemistry. Crit Rev Clin Lab Sci 1989;27:409–37.10.3109/10408368909106595Search in Google Scholar PubMed
19. IUPAC. Protocol for the design, conduct and interpretation of method performance studies. Pure Appl Chem 1995;67:331–43.Search in Google Scholar
20. Fraser CG. Biological variation: from principles to practice. Washington DC: AACC Press, 2001.Search in Google Scholar
21. Carlsen S, Petersen P, Skeie S, Skadberg O, Sandberg S. Within subject biological variation of glucose and HbA1c in healthy persons and in type 1 diabetes patients. Clin Chem Lab Med 2011;49:1501–7.10.1515/CCLM.2011.233Search in Google Scholar PubMed
22. Reed AH, Henry RJ, Mason WB. Influence of statistical method used on the resulting estimate of normal range. Clin Chem 1971;17:275–84.10.1093/clinchem/17.4.275Search in Google Scholar
23. Dixon WJ. Processing data for outliers. Biometrics 1953;9:74–89.10.2307/3001634Search in Google Scholar
24. Roraas T, Petersen PH, Sandberg S. Confidence intervals and power calculations for within-person biological variation: effect of analytical imprecision, number of replicates, number of samples, and number of individuals. Clin Chem 2012;58:1306–13.10.1373/clinchem.2012.187781Search in Google Scholar PubMed
25. Burdick RK, Graybill FA. Confidence intervals on variance components. New York: Marcel Dekker, 1992.10.1201/9781482277142Search in Google Scholar
26. Petersen PH, Fraser CG, Sandberg S, Goldschmidt H. The index of individuality is often a misinterpreted quantity characteristic. Clin Chem Lab Med 1999;37:655–61.10.1515/CCLM.1999.102Search in Google Scholar PubMed
27. Harris EK, Yasaka T. On the calculation of a “reference change” for comparing two consecutive measurements. Clin Chem 1983;29:25–30.10.1093/clinchem/29.1.25Search in Google Scholar
28. Aakre KM, Roraas T, Petersen PH, Svarstad E, Sellevoll H, Skadberg O, et al. Weekly and 90-minute biological variations in cardiac troponin t and cardiac troponin i in hemodialysis patients and healthy controls. Clin Chem 2014;60:838–47.10.1373/clinchem.2013.216978Search in Google Scholar PubMed
29. Solvik UO, Petersen PH, Monsen G, Stavelin AV, Sandberg S. Discrepancies in international normalized ratio results between instruments: a model to split the variation into subcomponents. Clin Chem 2010;56:1618–26.10.1373/clinchem.2010.146233Search in Google Scholar PubMed
30. McDonald JH. Handbook of biological statistics, 3rd ed. Baltimore, Maryland: Sparky House Publishing, 2014.Search in Google Scholar
31. Felding P, Tryding N, Hyltoft Petersen P, Horder M. Effects of posture on concentrations of blood constituents in healthy adults: practical application of blood specimen collection procedures recommended by the scandinavian committee on reference values. Scand J Clin Lab Invest 1980;40:615–21.10.3109/00365518009091972Search in Google Scholar PubMed
32. Druzd D, de Juan A, Scheiermann C. Circadian rhythms in leukocyte trafficking. Semin Immunopathol 2014;36:149–62.10.1007/s00281-013-0414-4Search in Google Scholar PubMed
33. Lasselin J, Rehman JU, Akerstedt T, Lekander M, Axelsson J. Effect of long-term sleep restriction and subsequent recovery sleep on the diurnal rhythms of white blood cell subpopulations. Brain Behav Immun 2015;47:93–9.10.1016/j.bbi.2014.10.004Search in Google Scholar PubMed
34. Mazzoccoli G, Correra M, Bianco G, De Cata A, Balzanelli M, Giuliani A, et al. Age-related changes of neuro-endocrine-immune interactions in healthy humans. J Biol Regul Homeost Agents 1997;11:143–7.Search in Google Scholar
35. Mazzoccoli G, Carughi S, Sperandeo M, Pazienza V, Giuliani F, Greco A. Alteration of circadian rhythmicity of cd3+cd4+ lymphocyte subpopulation in healthy aging. J Biol Regul Homeost Agents 2011;25:405–16.Search in Google Scholar
36. Fraser CG, Wilkinson SP, Neville RG, Knox JD, King JF, MacWalter RS. Biologic variation of common hematologic laboratory quantities in the elderly. Am J Clin Pathol 1989;92:465–70.10.1093/ajcp/92.4.465Search in Google Scholar PubMed
37. Iglesias N, Petersen PH, Ricos C. Power function of the reference change value in relation to cut-off points, reference intervals and index of individuality. Clin Chem Lab Med 2005;43:441–8.10.1515/CCLM.2005.078Search in Google Scholar PubMed
Supplemental Material:
The online version of this article (DOI: https://doi.org/10.1515/cclm-2016-0716) offers supplementary material, available to authorized users.
©2017 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorials
- Opportunities and drawbacks of nonstandard body fluid analysis
- How I first met Dr. Morton K. Schwartz
- Reviews
- Measurement of thyroglobulin, calcitonin, and PTH in FNA washout fluids
- Quality control materials for pharmacogenomic testing in the clinic
- Modulating thrombotic diathesis in hereditary thrombophilia and antiphospholipid antibody syndrome: a role for circulating microparticles?
- Opinion Papers
- Advances in laboratory diagnosis of hereditary spherocytosis
- Analytical performance specifications for external quality assessment – definitions and descriptions
- Genetics and Molecular Diagnostics
- Differences between quantification of genotype 3 hepatitis C virus RNA by Versions 1.0 and 2.0 of the COBAS AmpliPrep/COBAS TaqMan HCV Test
- General Clinical Chemistry and Laboratory Medicine
- Estimating the intra- and inter-individual imprecision of manual pipetting
- Effect of multiple freeze-thaw cycles on selected biochemical serum components
- The effect of storage temperature fluctuations on the stability of biochemical analytes in blood serum
- Comparison of ex vivo stability of copeptin and vasopressin
- Physiologic changes of urinary proteome by caffeine and excessive water intake
- Assessment of autoantibodies to interferon-ω in patients with autoimmune polyendocrine syndrome type 1: using a new immunoprecipitation assay
- Reference Values and Biological Variations
- Within-day biological variation and hour-to-hour reference change values for hematological parameters
- Relationship between anti-Müllerian hormone and antral follicle count across the menstrual cycle using the Beckman Coulter Access assay in comparison with Gen II manual assay
- Cardiovascular Diseases
- Low-grade inflammation and tryptophan-kynurenine pathway activation are associated with adverse cardiac remodeling in primary hyperparathyroidism: the EPATH trial
- Infectious Diseases
- Comparison between procalcitonin and C-reactive protein in predicting bacteremias and confounding factors: a case-control study
- Monitoring of procalcitonin but not interleukin-6 is useful for the early prediction of anastomotic leakage after colorectal surgery
- Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study
- Letters to the Editor
- Incidental findings of monoclonal proteins from carbohydrate-deficient transferrin analysis using capillary electrophoresis
- IgD-λ myeloma with extensive free light-chain excretion: a diagnostic pitfall in the identification of monoclonal gammopathies
- 25-Hydroxyvitamin D threshold values should be age-specific
- Effect of dabigatran treatment at therapeutic levels on point-of-care international normalized ratio (INR)
- Alkaline phosphatase activity – pH impact on the measurement result
- Cyst hydatid and cancer: the myth continues
- Role of activated platelets in severe acne scarring and adaptive immunity activation
- Towards a random-access LC-MS/MS model for busulfan analysis
Articles in the same Issue
- Frontmatter
- Editorials
- Opportunities and drawbacks of nonstandard body fluid analysis
- How I first met Dr. Morton K. Schwartz
- Reviews
- Measurement of thyroglobulin, calcitonin, and PTH in FNA washout fluids
- Quality control materials for pharmacogenomic testing in the clinic
- Modulating thrombotic diathesis in hereditary thrombophilia and antiphospholipid antibody syndrome: a role for circulating microparticles?
- Opinion Papers
- Advances in laboratory diagnosis of hereditary spherocytosis
- Analytical performance specifications for external quality assessment – definitions and descriptions
- Genetics and Molecular Diagnostics
- Differences between quantification of genotype 3 hepatitis C virus RNA by Versions 1.0 and 2.0 of the COBAS AmpliPrep/COBAS TaqMan HCV Test
- General Clinical Chemistry and Laboratory Medicine
- Estimating the intra- and inter-individual imprecision of manual pipetting
- Effect of multiple freeze-thaw cycles on selected biochemical serum components
- The effect of storage temperature fluctuations on the stability of biochemical analytes in blood serum
- Comparison of ex vivo stability of copeptin and vasopressin
- Physiologic changes of urinary proteome by caffeine and excessive water intake
- Assessment of autoantibodies to interferon-ω in patients with autoimmune polyendocrine syndrome type 1: using a new immunoprecipitation assay
- Reference Values and Biological Variations
- Within-day biological variation and hour-to-hour reference change values for hematological parameters
- Relationship between anti-Müllerian hormone and antral follicle count across the menstrual cycle using the Beckman Coulter Access assay in comparison with Gen II manual assay
- Cardiovascular Diseases
- Low-grade inflammation and tryptophan-kynurenine pathway activation are associated with adverse cardiac remodeling in primary hyperparathyroidism: the EPATH trial
- Infectious Diseases
- Comparison between procalcitonin and C-reactive protein in predicting bacteremias and confounding factors: a case-control study
- Monitoring of procalcitonin but not interleukin-6 is useful for the early prediction of anastomotic leakage after colorectal surgery
- Activation of the tryptophan/serotonin pathway is associated with severity and predicts outcomes in pneumonia: results of a long-term cohort study
- Letters to the Editor
- Incidental findings of monoclonal proteins from carbohydrate-deficient transferrin analysis using capillary electrophoresis
- IgD-λ myeloma with extensive free light-chain excretion: a diagnostic pitfall in the identification of monoclonal gammopathies
- 25-Hydroxyvitamin D threshold values should be age-specific
- Effect of dabigatran treatment at therapeutic levels on point-of-care international normalized ratio (INR)
- Alkaline phosphatase activity – pH impact on the measurement result
- Cyst hydatid and cancer: the myth continues
- Role of activated platelets in severe acne scarring and adaptive immunity activation
- Towards a random-access LC-MS/MS model for busulfan analysis