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, Steven J. R. Meex*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)1013-1024
Number of pages12
JournalClinical Chemistry and Laboratory Medicine
Issue number7
Publication statusPublished - Jul 2017


  • biological variation
  • diurnal rhythm
  • hematology
  • reference change value

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