Abstract
Objectives
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.
Methods
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.
Results
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.
Conclusions
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.
Acknowledgments
We would like to thank the healthy volunteers for providing their blood for this study.
-
Research funding: None declared.
-
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.
-
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.
-
Informed consent: Informed consent was obtained from all individuals included in this study.
-
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).
References
1. Fraser, CG, Harris, EK. Generation and application of data on biological variation in clinical chemistry. Crit Rev Clin Lab Sci 1989;27:409–37. https://doi.org/10.3109/10408368909106595.Search in Google Scholar PubMed
2. Fraser, CG. Biological variation: a rapidly evolving aspect of laboratory medicine. J Lab Precis Med 2017;2:35–5. https://doi.org/10.21037/jlpm.2017.06.09.Search in Google Scholar
3. Sandberg, S, Fraser, CG, Horvath, AR, Jansen, R, Jones, G, Oosterhuis, W, et al.. Defining analytical performance specifications: consensus statement from the 1st strategic conference of the European federation of clinical chemistry and laboratory medicine. Clin Chem Lab Med 2015;53:833–5. https://doi.org/10.1515/cclm-2015-0067.Search in Google Scholar PubMed
4. Bartlett, WA, Braga, F, Carobene, A, Coşkun, 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. https://doi.org/10.1515/cclm-2014-1127.Search in Google Scholar PubMed
5. Aarsand, AK, Røraas, T, Fernandez-Calle, P, Ricos, C, Díaz-Garzón, J, Jonker, N, et al.. The biological variation data critical appraisal checklist: a standard for evaluating studies on biological variation. Clin Chem 2018;64:501–14. https://doi.org/10.1373/clinchem.2017.281808.Search in Google Scholar PubMed
6. Connors, JM. Thrombophilia testing and venous thrombosis. N Engl J Med 2017;377:1177–87. https://doi.org/10.1056/nejmra1700365.Search in Google Scholar PubMed
7. Mairesse, A, Bayart, JL, Desmet, S, Lopes Dos Santos, H, Saussoy, P, Defour, JP, et al.. Biological variation data and analytical specification goal estimates of the thrombin generation assay with and without thrombomodulin in healthy individuals. Int J Lab Hematol 2021;43:450–7. https://doi.org/10.1111/ijlh.13388.Search in Google Scholar PubMed
8. Braga, F, Panteghini, M. Generation of data on within-subject biological variation in laboratory medicine: an update. Crit Rev Clin Lab Sci 2016;53:313–25. https://doi.org/10.3109/10408363.2016.1150252.Search in Google Scholar PubMed
9. Ricós Carmen, PC, Minchinela, J, Alvarez, V, Simon, M, Biosca, C, Domenech, M, et al.. Application of biological variation - a review. Biochem Med 2009;19:250–9. https://doi.org/10.11613/bm.2009.023.Search in Google Scholar
10. Carobene, A, Strollo, M, Jonker, N, Barla, G, Bartlett, WA, Sandberg, S, et al.. Sample collections from healthy volunteers for biological variation estimates’ update: a new project undertaken by the working group on biological variation established by the European federation of clinical chemistry and laboratory medicine. Clin Chem Lab Med 2016;54:1599–608. https://doi.org/10.1515/cclm-2016-0035.Search in Google Scholar PubMed
11. Institute, CALS. Procedures for the collection of diagnostic blood specimens by venipuncture; Approved standard-sixth edition; 2007.Search in Google Scholar
12. Woodhams, B, Girardot, O, Blanco, MJ, Colesse, G, Gourmelin, Y. Stability of coagulation proteins in frozen plasma. Blood Coagul Fibrinolysis 2001;12:229–36. https://doi.org/10.1097/00001721-200106000-00002.Search in Google Scholar
13. Ceriotti, F, Díaz-Garzón Marco, J, Fernández-Calle, P, Maregnani, A, Aarsand, AK, Coskun, A, et al.. The European Biological Variation Study (EuBIVAS): weekly biological variation of cardiac troponin I estimated by the use of two different high-sensitivity cardiac troponin I assays. Clin Chem Lab Med 2020;58:1741–7. https://doi.org/10.1515/cclm-2019-1182.Search in Google Scholar
14. Fernández-Calle, P, Díaz-Garzón, J, Bartlett, W, Sandberg, S, Braga, F, Beatriz, B, et al.. Biological variation estimates of thyroid related measurands - meta-analysis of BIVAC compliant studies. Clin Chem Lab Med 2022;60:483–93. https://doi.org/10.1515/cclm-2021-0904.Search in Google Scholar
15. Fraser, CG, Hyltoft Petersen, P, Libeer, JC, Ricos, C. Proposals for setting generally applicable quality goals solely based on biology. Ann Clin Biochem 1997;34:8–12. https://doi.org/10.1177/000456329703400103.Search in Google Scholar
16. de Maat, MP, van Schie, M, Kluft, C, Leebeek, FW, Meijer, P. Biological variation of hemostasis variables in thrombosis and bleeding: consequences for performance specifications. Clin Chem 2016;62:1639–46. https://doi.org/10.1373/clinchem.2016.261248.Search in Google Scholar
17. Chen, Q, Shou, W, Wu, W, Guo, Y, Zhang, Y, Huang, C, et al.. Biological and analytical variations of 16 parameters related to coagulation screening tests and the activity of coagulation factors. Semin Thromb Hemost 2015;41:336–41. https://doi.org/10.1055/s-0034-1543994.Search in Google Scholar
18. Chambless, LE, McMahon, R, Wu, K, Folsom, A, Finch, A, Shen, YL. Short-term intraindividual variability in hemostasis factors. The ARIC study. Atherosclerosis risk in communities intraindividual variability study. Ann Epidemiol 1992;2:723–33. https://doi.org/10.1016/1047-2797(92)90017-k.Search in Google Scholar
19. Melzi d’Eril, G, Anesi, A, Rizzo, V, Trotti, R. Biological variation in protein C, protein S and antithrombin concentrations in plasma of healthy subjects. Eur J Clin Chem Clin Biochem 1997;35:257–60.10.1515/cclm.1997.35.4.257Search in Google Scholar PubMed
20. Wada, Y, Kurihara, M, Toyofuku, M, Kawamura, M, Iida, H, Kayamori, Y, et al.. Analytical goals for coagulation tests based on biological variation. Clin Chem Lab Med 2004;42:79–83. https://doi.org/10.1515/cclm.2004.015.Search in Google Scholar
21. Aarsand, AK, Kristoffersen, AH, Sandberg, S, Støve, B, Coşkun, A, Fernandez-Calle, P, et al.. The European biological variation study (EuBIVAS): biological variation data for coagulation markers estimated by a bayesian model. Clin Chem 2021;67:1259–70. https://doi.org/10.1093/clinchem/hvab100.Search in Google Scholar PubMed
22. Westgard, QC; 2019. Available from: https://www.westgard.com/biodatabase1.htm [accessed on 28 February 2022].Search in Google Scholar
23. Makris, M, Oldenburg, J, Mauser-Bunschoten, EP, Peerlinck, K, Castaman, G, Fijnvandraat, K. The definition, diagnosis and management of mild hemophilia A: communication from the SSC of the ISTH. J Thromb Haemostasis 2018;16:2530–3. https://doi.org/10.1111/jth.14315.Search in Google Scholar PubMed
24. Walton, RM. Subject-based reference values: biological variation, individuality, and reference change values. Vet Clin Pathol 2012;41:175–81. https://doi.org/10.1111/j.1939-165x.2012.00414.x.Search in Google Scholar
25. Benson, G, Auerswald, G, Dolan, G, Duffy, A, Hermans, C, Ljung, R, et al.. Diagnosis and care of patients with mild haemophilia: practical recommendations for clinical management. Blood Transfus 2018;16:535–44.Search in Google Scholar
26. Senzolo, M, Burra, P, Cholongitas, E, Burroughs, AK. New insights into the coagulopathy of liver disease and liver transplantation. World J Gastroenterol 2006;12:7725–36. https://doi.org/10.3748/wjg.v12.i48.7725.Search in Google Scholar PubMed PubMed Central
27. Elinav, E, Ben-Dov, I, Hai-Am, E, Ackerman, Z, Ofran, Y. The predictive value of admission and follow up factor V and VII levels in patients with acute hepatitis and coagulopathy. J Hepatol 2005;42:82–6. https://doi.org/10.1016/j.jhep.2004.09.009.Search in Google Scholar PubMed
28. Montagnana, M, Salvagno, GL, Lippi, G. Circadian variation within hemostasis: an underrecognized link between biology and disease? Semin Thromb Hemost 2009;35:23–33. https://doi.org/10.1055/s-0029-1214145.Search in Google Scholar PubMed
© 2022 Walter de Gruyter GmbH, Berlin/Boston
