Home Biological variation and reference change values of common clinical chemistry and haematologic laboratory analytes in the elderly population
Article
Licensed
Unlicensed Requires Authentication

Biological variation and reference change values of common clinical chemistry and haematologic laboratory analytes in the elderly population

  • Daniel Pineda-Tenor EMAIL logo , Emilio José Laserna-Mendieta , Jesús Timón-Zapata , Laura Rodelgo-Jiménez , Raquel Ramos-Corral , Antonio Recio-Montealegre and Manuel Gómez-Serranillos Reus
Published/Copyright: March 22, 2013
Become an author with De Gruyter Brill
Submit Manuscript Author Information
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 51 Issue 4

Abstract

Background: Biological variation (BV) and reference change values (RCVs) have been widely described for the general population, but the use of these data derived from adults in the elderly population is a controversial issue. We determined the within- and between-subject BV and RCV in both elderly and young people and compared them with previously published analyses.

Methods: Samples were collected from 135 volunteers over 80 years of age at weekly intervals over 4 weeks. Eighteen biochemical and eight haematological analytes were measured. The Fraser and Harris methods were used to calculate the components of BV and RCV. To perform a comparative analysis, a reference group of 118 young subjects was studied under the same conditions.

Results: The obtained coefficients of BV showed statistical differences in many cases, but in general, both the elderly and young patient data fall within the ranges previously described for the general population. The indexes of individuality for the analytes investigated did not exceed 1.4 in any case and were <0.6 for some analytes. The RCVs derived from elderly subjects were similar to those published in the young population, both in healthy and diseased individuals.

Conclusions: The strong individuality observed supports the preferential use of RCVs rather than population-based reference intervals in elderly people. For most of the analytes studied, data from the young population can be applied to elderly people, but the specific elderly coefficients of BV and RCVs are a recommended option.

Keywords: biological variation; critical difference; elderly; index of individuality; reference change value
Corresponding author: Dr. Daniel Pineda-Tenor, Clinical Analysis Service, Hospital Virgen de la Salud, Toledo Hospital Complex, Avenida de Barber s/n, CP:45004, Toledo, Spain

The authors thank the laboratory technical staff for their valuable assistance. This study was supported by the J.L. Castaño Foundation.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Funding: The work was supported by the J.L. Castaño Foundation.

Ethical approval: The study was carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving human subjects.

References

1. United Nations Department of Economic and Social Affairs, Population Division. World population prospects: The 2010 revision, vol I: comprehensive tables. ST/ESA/SER.A/313.Search in Google Scholar

2. Morgan DB. The impact of ageing-present and future. Ann Clin Biochem 1983;20:257–61.10.1177/000456328302000501Search in Google Scholar PubMed

3. 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

4. Ricos C, Cava F, Garcia-Lario JV, Hernandez A, Iglesias N, Jimenez CV, etal. The reference change value: a proposal to interpret laboratory reports in serial testing based on biological variation. Scand J Clin Lab Invest 2004;64:175–84.10.1080/00365510410004885Search in Google Scholar PubMed

5. Padro-Miquel A, Rigo-Bonnin R, Fuentes-Arderiu X. Significance of a change between two consecutive measured values. Scand J Clin Lab Invest 2012;72:169–72.10.3109/00365513.2011.637575Search in Google Scholar PubMed

6. Biosca C, Ricos C, Lauzurica R, Galimany R, Hyltoft Petersen P. Reference change value concept combining two delta values to predict crises in renal posttransplantation. Clin Chem 2001;47:2146–8.10.1093/clinchem/47.12.2146Search in Google Scholar PubMed

7. Ricos C, Iglesias N, Garcia-Lario JV, Simon M, Cava F, Hernandez A, etal. Within-subject biological variation in disease: collated data and clinical consequences. Ann Clin Biochem 2007;44:343–52.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000247943400004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1258/000456307780945633Search in Google Scholar PubMed

8. Fraser CG. Age-related changes in laboratory test results. Clinical implications. Drugs Aging 1993;3:246–57.10.2165/00002512-199303030-00006Search in Google Scholar PubMed

9. Harris EK. Statistical aspects of reference values in clinical pathology. Prog Clin Pathol 1981;8:45–66.Search in Google Scholar PubMed

10. Plebani M, Lippi G. Biological variation and reference change values: an essential piece of the puzzle of laboratory testing. Clin Chem Lab Med 2012;50:189–90.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000301991300001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar PubMed

11. Harris EK. Effects of intra- and interindividual variation on the appropriate use of normal ranges. Clin Chem 1974;20:1535–42.10.1093/clinchem/20.12.1535Search in Google Scholar PubMed

12. Fraser CG. Inherent biological variation and reference values. Clin Chem Lab Med 2004;42:758–64.10.1515/CCLM.2004.128Search in Google Scholar PubMed

13. 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 PubMed

14. Fraser CG. Reference change values: the way forward in monitoring. Ann Clin Biochem 2009;46:264–5.10.1258/acb.2009.009006http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000266289800019&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar PubMed

15. Biosca C, Ricos C, Jimenez CV, Lauzurica R, Galimany R. Are equally spaced specimen collections necessary to assess biological variation? Evidence from renal transplant recipients. Clin Chim Acta 2000;301:79–85.10.1016/S0009-8981(00)00346-6Search in Google Scholar PubMed

16. Ricos C, Jimenez CV, Hernandez A, Simon M, Perich C, Alvarez V, etal. Biological variation in urine samples used for analyte measurements. Clin Chem 1994;40:472–7.10.1093/clinchem/40.3.472Search in Google Scholar PubMed

17. Fraser CG, Kallner A, Kenny D, Petersen PH. Introduction strategies to set global quality specifications in laboratory medicine. Scand J Clin Lab Invest 1999;59:477–8.10.1080/00365519950185184Search in Google Scholar

18. Fraser CG, Cummings ST, Wilkinson SP, Neville RG, Knox JD, Ho O, etal. Biological variability of 26 clinical chemistry analytes in elderly people. Clin Chem 1989;35:783–6.10.1093/clinchem/35.5.783Search in Google Scholar PubMed

19. 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

20. Ricos C, Alvarez V, Cava F, Garcia-Lario JV, Hernandez A, Jimenez CV, etal. Update 2012 (www.westgard.com) from the original paper: current databases on biological variation: pros, cons and progress. Scand J Clin Lab Invest 1999;59:491–500.10.1080/00365519950185229Search in Google Scholar PubMed

21. Costongs GM, Janson PC, Bas BM, Hermans J, van Wersch JW, Brombacher PJ. Short-term and long-term intra-individual variations and critical differences of clinical chemical laboratory parameters. J Clin Chem Clin Biochem 1985;23:7–16.10.1515/cclm.1985.23.7.405Search in Google Scholar PubMed

22. Costongs GM, Janson PC, Bas BM, Hermans J, Brombacher PJ, van Wersch JW. Short-term and long-term intra-individual variations and critical differences of haematological laboratory parameters. J Clin Chem Clin Biochem 1985;23:69–76.10.1515/cclm.1985.23.2.69Search in Google Scholar PubMed

23. Harris EK, Kanofsky P, Shakarji G, Cotlove E. Biological and analytic components of variation in long-term studies of serum constituents in normal subjects. II. Estimating biological components of variation. Clin Chem 1970;16:1022–7.10.1093/clinchem/16.12.1022Search in Google Scholar PubMed

24. Borel MJ, Smith SM, Derr J, Beard JL. Day-to-day variation in iron-status indices in healthy men and women. Am J Clin Nutr 1991;54:729–35.10.1093/ajcn/54.4.729Search in Google Scholar PubMed

25. Van Steirteghem AC, Robertson EA, Young DS. Variance components of serum constituents in healthy individuals. Clin Chem 1978;24:212–22.10.1093/clinchem/24.2.212Search in Google Scholar PubMed

26. Sebastian-Gambaro MA, Liron-Hernandez FJ, Fuentes-Arderiu X. Intra- and inter-individual biological variability data bank. Eur J Clin Chem Clin Biochem 1997;35:845–52.Search in Google Scholar

27. Fuentes-Arderiu X. Variability of the biological variation. Scand J Clin Lab Invest 2002;62:561–3.10.1080/003655102321004585Search in Google Scholar PubMed

28. Lacher DA, Barletta J, Hughes JP. Biological variation of hematology tests based on the 1999–2002 national health and nutrition examination survey. National Health Statistics Reports 2012;54:1–11.Search in Google Scholar

29. Fraser CG. The application of theoretical goals based on biological variation data in proficiency testing. Arch Pathol Lab Med 1988;112:404–15.Search in Google Scholar PubMed

30. 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 PubMed

31. Eckfeldt JH, Chambless LE, Shen YL. Short-term, within-person variability in clinical chemistry test results. Experience from the Atherosclerosis Risk in Communities Study. Arch Pathol Lab Med 1994;118:496–500.Search in Google Scholar PubMed

32. Smith SJ, Cooper GR, Myers GL, Sampson EJ. Biological variability in concentrations of serum lipids: sources of variation among results from published studies and composite predicted values. Clin Chem 1993;39:1012–22.10.1093/clinchem/39.6.1012Search in Google Scholar PubMed

33. 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.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000280844300020&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1007/s00421-010-1493-8Search in Google Scholar PubMed

34. Young DS, Harris EK, Cotlove E. Biological and analytic components of variation in long-term studies of serum constituents in normal subjects. IV. Results of a study designed to eliminate long-term analytic deviations. Clin Chem 1971;17:403–10.10.1093/clinchem/17.5.403Search in Google Scholar PubMed

35. Williams GZ, Widdowson GM, Penton J. Individual character of variation in time-series studies of healthy people: II. Differences in values for clinical chemical analytes in serum among demographic groups, by age and sex. Clin Chem 1978;24:313–20.10.1093/clinchem/24.2.313Search in Google Scholar PubMed

36. Jimenez CV. Variabilidad biológica intraindividual de las magnitudes citohematológicas como objetivo de calidad analítica. Quim Clin 1992;11:147–50.Search in Google Scholar

37. Fraser CG, Hearne CR. Components of variance of some plasma constituents in patients with myocardial infarction. Ann Clin Biochem 1982;19:431–4.10.1177/000456328201900608Search in Google Scholar PubMed

38. Holzel WG. Influence of hypertension and antihypertensive drugs on the biological intra-individual variation of electrolytes and lipids in serum. Clin Chem 1988;34:1485–8.10.1093/clinchem/34.7.1485Search in Google Scholar PubMed

39. Holzel WG. Intra-individual variation of some analytes in serum of patients with insulin-dependent diabetes mellitus. Clin Chem 1987;33:57–61.10.1093/clinchem/33.1.57Search in Google Scholar PubMed

40. Fraser CG, Williams P. Short-term biological variation of plasma analytes in renal disease. Clin Chem 1983;29:508–10.10.1093/clinchem/29.3.508Search in Google Scholar PubMed

41. Holzel WG. Intra-individual variation of some analytes in serum of patients with chronic renal failure. Clin Chem 1987;33:670–3.10.1093/clinchem/33.5.670Search in Google Scholar PubMed

42. Holzel WG. Intra-individual variation of analytes in serum from patients with chronic liver diseases. Clin Chem 1987;33:1133–6.10.1093/clinchem/33.7.1133Search in Google Scholar PubMed

43. Desmeules P, Cousineau J, Allard P. Biological variation of glycated haemoglobin in a paediatric population and its application to calculation of significant change between results. Ann Clin Biochem 2010;47:35–8.10.1258/acb.2009.009113http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000275482400007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar PubMed

44. Rotterdam EP, Katan MB, Knuiman JT. Importance of time interval between repeated measurements of total or high-density lipoprotein cholesterol when estimating an individual’s baseline concentrations. Clin Chem 1987;33:1913–5.10.1093/clinchem/33.10.1913Search in Google Scholar

45. Cotlove E, Harris EK, Williams GZ. Biological and analytic components of variation in long-term studies of serum constituents in normal subjects. 3. Physiological and medical implications. Clin Chem 1970;16:1028–32.10.1093/clinchem/16.12.1028Search in Google Scholar PubMed

46. Williams GZ, Young DS, Stein MR, Cotlove E. Biological and analytic components of variation in long-term studies of serum constituents in normal subjects. I. Objectives, subject selection, laboratory procedures, and estimation of analytic deviation. Clin Chem 1970;16:1016–21.10.1093/clinchem/16.12.1016Search in Google Scholar PubMed

47. Fuentes-Arderiu X, Gonzalez-de-la-Presa B. Interchangeability of estimates of day-to-day imprecision between commercial control materials and serum pools. Clin Chem 2002;48: 573–4.10.1093/clinchem/48.3.573Search in Google Scholar

48. U.S. Department of Health and Human Services. Medicare M, and CLIA Programs. Regulations implementing the clinical laboratory improvement amendments of 1988 (CLIA). Final Rule. Fed Regist 1992;57:7002–186.Search in Google Scholar
Received: 2012-10-15
Accepted: 2012-12-26
Published Online: 2013-03-22
Published in Print: 2013-04-01

©2013 by Walter de Gruyter Berlin Boston

Articles in the same Issue

  1. Letters to the Editor
  2. Missing agreement between the two IMMULITE® PSA assays
  3. “Cerebrovascular stressing”: dipyridamole-induced S100B elevation predicts ischemic cerebrovascular events
  4. Discrepancy in lamellar body counts (LBCs) between the Sysmex XE-2100 and Sysmex XT-2000i instruments
  5. Interphase fluorescent in situ hybridization detection of the 7q11.23 chromosomal inversion in a clinical laboratory: automated versus manual scoring
  6. Adrenocorticotropic hormone stability in preanalytical phase depends on temperature and proteolytic enzyme inhibitor
  7. The impact on costs and efficiency of reducing the number of collected tubes
  8. Improved software on the Sysmex XE-5000 BF mode for counting leukocytes in cerebrospinal fluid
  9. First trimester placental growth factor and soluble fms-like tyrosine kinase 1 are significantly related to PAPP-A levels
  10. Preliminary evaluation of complete blood cell count on Mindray BC-6800
  11. Rational use of laboratory tests: albuminuria
  12. Masthead
  13. Masthead
  14. Editorials
  15. Fifty years of CCLM – invitation to join us for a reception in Milan
  16. Personalized (laboratory) medicine: a bridge to the future
  17. PSA, PCA3 and the phi losophy of prostate cancer management
  18. Reviews
  19. Gender medicine: a task for the third millennium
  20. Evaluation of [−2] proPSA and Prostate Health Index (phi) for the detection of prostate cancer: a systematic review and meta-analysis
  21. Harmonization in laboratory medicine: the complete picture
  22. Opinion Papers
  23. Glycemic control in the clinical management of diabetic patients
  24. Time for a conceptual shift in assessment of internal quality control for whole blood or cell-based testing systems? An evaluation using platelet function and the PFA-100 as a case example
  25. Guidelines and Recommendations
  26. A position paper of the EFLM Committee on Education and Training and Working Group on Distance Education Programmes/E-Learning: developing an e-learning platform for the education of stakeholders in laboratory medicine
  27. General Clinical Chemistry and Laboratory Medicine
  28. A novel weighted cumulative delta-check method for highly sensitive detection of specimen mix-up in the clinical laboratory
  29. Identification and quantification of hemoglobins in whole blood: the analytical and organizational aspects of Capillarys 2 Flex Piercing compared with agarose electrophoresis and HPLC methods
  30. Determination of the fatty acid profile of neutral lipids, free fatty acids and phospholipids in human plasma
  31. Urinary iodine concentrations of pregnant women in Ukraine
  32. Delay in the measurement of eosin-5′-maleimide (EMA) binding does not affect the test result for the diagnosis of hereditary spherocytosis
  33. Faecal calprotectin: comparative study of the Quantum Blue rapid test and an established ELISA method
  34. Target analyte quantification by isotope dilution LC-MS/MS directly referring to internal standard concentrations – validation for serum cortisol measurement
  35. Reference Values and Biological Variations
  36. Reference values and upper reference limits for 26 trace elements in the urine of adults living in Belgium
  37. Biological variation and reference change values of common clinical chemistry and haematologic laboratory analytes in the elderly population
  38. Indirect determination of pediatric blood count reference intervals
  39. Cancer Diagnostics
  40. Suitability of quality control materials for prostate-specific antigen (PSA) measurement: inter-method variability of common tumor marker control materials
  41. Prostate cancer antigen 3 (PCA3) RNA detection in blood and tissue samples for prostate cancer diagnosis
  42. Serum levels of cancer biomarkers in diabetic and non-diabetic proteinuric patients: a preliminary study
  43. Infectious Diseases
  44. Polymorphic mononuclear neutrophils CD64 index for diagnosis of sepsis in postoperative surgical patients and critically ill patients
  45. Plasma long pentraxin 3 (PTX3) concentration is a novel marker of disease activity in patients with community-acquired pneumonia
https://doi.org/10.1515/cclm-2012-0701
Keywords for this article
biological variation; critical difference; elderly; index of individuality; reference change value

Articles in the same Issue

  1. Letters to the Editor
  2. Missing agreement between the two IMMULITE® PSA assays
  3. “Cerebrovascular stressing”: dipyridamole-induced S100B elevation predicts ischemic cerebrovascular events
  4. Discrepancy in lamellar body counts (LBCs) between the Sysmex XE-2100 and Sysmex XT-2000i instruments
  5. Interphase fluorescent in situ hybridization detection of the 7q11.23 chromosomal inversion in a clinical laboratory: automated versus manual scoring
  6. Adrenocorticotropic hormone stability in preanalytical phase depends on temperature and proteolytic enzyme inhibitor
  7. The impact on costs and efficiency of reducing the number of collected tubes
  8. Improved software on the Sysmex XE-5000 BF mode for counting leukocytes in cerebrospinal fluid
  9. First trimester placental growth factor and soluble fms-like tyrosine kinase 1 are significantly related to PAPP-A levels
  10. Preliminary evaluation of complete blood cell count on Mindray BC-6800
  11. Rational use of laboratory tests: albuminuria
  12. Masthead
  13. Masthead
  14. Editorials
  15. Fifty years of CCLM – invitation to join us for a reception in Milan
  16. Personalized (laboratory) medicine: a bridge to the future
  17. PSA, PCA3 and the phi losophy of prostate cancer management
  18. Reviews
  19. Gender medicine: a task for the third millennium
  20. Evaluation of [−2] proPSA and Prostate Health Index (phi) for the detection of prostate cancer: a systematic review and meta-analysis
  21. Harmonization in laboratory medicine: the complete picture
  22. Opinion Papers
  23. Glycemic control in the clinical management of diabetic patients
  24. Time for a conceptual shift in assessment of internal quality control for whole blood or cell-based testing systems? An evaluation using platelet function and the PFA-100 as a case example
  25. Guidelines and Recommendations
  26. A position paper of the EFLM Committee on Education and Training and Working Group on Distance Education Programmes/E-Learning: developing an e-learning platform for the education of stakeholders in laboratory medicine
  27. General Clinical Chemistry and Laboratory Medicine
  28. A novel weighted cumulative delta-check method for highly sensitive detection of specimen mix-up in the clinical laboratory
  29. Identification and quantification of hemoglobins in whole blood: the analytical and organizational aspects of Capillarys 2 Flex Piercing compared with agarose electrophoresis and HPLC methods
  30. Determination of the fatty acid profile of neutral lipids, free fatty acids and phospholipids in human plasma
  31. Urinary iodine concentrations of pregnant women in Ukraine
  32. Delay in the measurement of eosin-5′-maleimide (EMA) binding does not affect the test result for the diagnosis of hereditary spherocytosis
  33. Faecal calprotectin: comparative study of the Quantum Blue rapid test and an established ELISA method
  34. Target analyte quantification by isotope dilution LC-MS/MS directly referring to internal standard concentrations – validation for serum cortisol measurement
  35. Reference Values and Biological Variations
  36. Reference values and upper reference limits for 26 trace elements in the urine of adults living in Belgium
  37. Biological variation and reference change values of common clinical chemistry and haematologic laboratory analytes in the elderly population
  38. Indirect determination of pediatric blood count reference intervals
  39. Cancer Diagnostics
  40. Suitability of quality control materials for prostate-specific antigen (PSA) measurement: inter-method variability of common tumor marker control materials
  41. Prostate cancer antigen 3 (PCA3) RNA detection in blood and tissue samples for prostate cancer diagnosis
  42. Serum levels of cancer biomarkers in diabetic and non-diabetic proteinuric patients: a preliminary study
  43. Infectious Diseases
  44. Polymorphic mononuclear neutrophils CD64 index for diagnosis of sepsis in postoperative surgical patients and critically ill patients
  45. Plasma long pentraxin 3 (PTX3) concentration is a novel marker of disease activity in patients with community-acquired pneumonia
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 19.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2012-0701/html
Scroll to top button