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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

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Volume 56, Issue 6


Short- and medium-term biological variation estimates of red blood cell and reticulocyte parameters in healthy subjects

Sabrina Buoro
  • Corresponding author
  • Clinical Chemistry Laboratory, Papa Giovanni XXIII Hospital, Piazza OMS, 1 – 24127 Bergamo, Italy, Phone: (+039) 0352674550, Fax: (+039) 0352674939
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Anna Carobene / Michela Seghezzi / Barbara Manenti / Paola Dominoni / Aurelio Pacioni / Ferruccio Ceriotti
  • Central Laboratory, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Cosimo Ottomano / Giuseppe LippiORCID iD: http://orcid.org/0000-0001-9523-9054
Published Online: 2018-01-05 | DOI: https://doi.org/10.1515/cclm-2017-0902



The integrated evaluation of traditional and innovative red blood cell (RBC) and reticulocyte parameters is a rapid, inexpensive and non-invasive diagnostic tools for differential diagnosis and follow-up of anemia and other pathological conditions needing bone marrow erythropoiesis assessment. Therefore, estimating the biological variation (BV) of these parameters is essential for evaluating the analytical performance of hematological analyzers, and for enabling accurate data interpretation and appropriate clinical management. This study aims to define short- and medium-term BV estimates and reference change value (RCV) of RBC and reticulocyte parameters.


Twenty-one healthy volunteers participated in the assessment of medium-term BV (blood sampling once/week, five consecutive weeks) and 22 volunteers in the assessment of short-term BV (blood sampling once/day, five consecutive days) using Sysmex XN. Outlier analysis was performed before CV-ANOVA, to determine BV estimates with confidence intervals (CI).


Medium- and short-term within-subject BV were between 0.3% and 16.4% and 0.2%–10.4% (MCH and IRF), respectively, whereas medium and short-term between-subjects BV ranged between 0.9% and 66.6% (MCHC and Micro-R) and 1.4%–43.6% (MCHC and IRF), respectively. The RCVs were similar for all parameters in both arms of the study, except for hemoglobin, RDW-CV and MCV.


This study allowed for estimating the BV of many RBC and reticulocyte parameters, some of which have not been currently explored. For RBC, hemoglobin, RDW-CV and MCV it seems advisable to use RCV calculated according to monitoring time and/or differentiated by sex. As regards analytical goals, we suggest using the most stringent targets found in the short-term arm of this study.

This article offers supplementary material which is provided at the end of the article.

Keywords: biological variation; hematology analyzer; hemoglobin; red blood cell; reference change value; RET-He; reticulocyte; XN


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About the article

Received: 2017-10-06

Accepted: 2017-11-22

Published Online: 2018-01-05

Published in Print: 2018-05-24

Author contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following three requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.

Research funding: None declared.

Employment or leadership: Aurelio Pacioni is an employee of DASIT, the Italian distributor for Sysmex.

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.

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 56, Issue 6, Pages 954–963, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2017-0902.

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