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Licensed Unlicensed Requires Authentication Published by De Gruyter June 27, 2022

Short-term biological variation study of plasma hemophilia and thrombophilia parameters in a population of apparently healthy Caucasian adults

  • Alice Brochier ORCID logo , Antoine Mairesse , Pascale Saussoy , Christel Gavard , Sandrine Desmet , Cédric Hermans , Damien Gruson and Marie-Astrid van Dievoet EMAIL logo



Biological variation (BV) data obtained in a standardized way is valuable to assess the analytical requirements and the utility of a reference interval. Our study aimed to determine the short-term BV of thrombophilia (protein S, protein C, activated protein C resistance (APCR) and factor VIII) and hemophilia (factors VIII, IX and XI) parameters in plasma. Coagulation factors V and XII were also evaluated. Based on the obtained data, we assessed analytical performance specifications for the parameters. Finally, we intended to provide a robust tool for comparison of serial measurements of factors V, VIII, IX and XI.


A blood draw was performed weekly in 19 apparently healthy Caucasian adults for five weeks at Saint-Luc University Hospital (Brussels, Belgium). Parameters were measured in duplicate. BV components were calculated with a nested analysis of variance after exclusion of outliers.


The analytical coefficient of variation (CV) varied from 1.5 to 4.6%, the within-subject CV from 1.6 to 8.9% and the between-subject CV from 3.8 to 24.1%. All parameters showed high individuality. For most parameters, the analytical goal was met with our assays. Reference change values (RCV) of −16.7% to +20.0%, −20.7% to +26.0%, −15.3% to +18.1% and −13.1% to +15.1% were obtained for factors V, VIII, IX and XI respectively.


All studied parameters were highly individualized. The assessment of BV data can guide setting analytical goal specifications. Comparison of serial measurements in the follow-up of patients suffering from hepatic failure or mild hemophilia is facilitated by evaluation of the RCV.

Corresponding author: Marie-Astrid van Dievoet, Hematology Department of Laboratory Medicine, Saint- Luc University Hospital, Avenue Hippocrate 10, 1200 Brussels, Belgium, Phone: +32 2 764 67 45, E-mail:


We would like to thank the healthy volunteers for providing their blood for this study.

  1. Research funding: None declared.

  2. Author contributions: A. Brochier analyzed the data and wrote the paper. A. Brochier made the figures. A. Mairesse, C. Gavard and S. Desmet provided the samples and performed the assays. M-A van Dievoet, C. Hermans, P. Saussoy and D. Gruson revised the content and gave final approval of the submitted version. All authors approved the final version.

  3. Competing interests: A. Brochier, A. Mairesse, C. Gavard, S. Desmet, P. Saussoy, C. Hermans, D. Gruson and M-A. van Dievoet declare that Werfen (Barcelona, Spain) has provided the reagents used in this study.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The research related to human use has complied with all the relevant national regulations, institutional policies, and in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ local Ethics Committee (2019/29JUL/340).


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Received: 2022-04-19
Accepted: 2022-06-20
Published Online: 2022-06-27
Published in Print: 2022-08-26

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