{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T02:23:11Z","timestamp":1781749391093,"version":"3.54.5"},"reference-count":28,"publisher":"Walter de Gruyter GmbH","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_cclm-2022-0377_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2022-0377_abs_002\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2022-0377_abs_003\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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\u00a0analytical goal was met with our assays. Reference change\u00a0values (RCV) of\u00a0\u221216.7% to +20.0%,\u00a0\u221220.7% to +26.0%,\u00a0\u221215.3% to +18.1% and\u00a0\u221213.1% to +15.1% were obtained for factors V, VIII, IX and XI respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2022-0377_abs_004\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/cclm-2022-0377","type":"journal-article","created":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T15:46:00Z","timestamp":1656171960000},"page":"1409-1415","source":"Crossref","is-referenced-by-count":4,"title":["Short-term biological variation study of plasma hemophilia and thrombophilia parameters in a population of apparently healthy Caucasian adults"],"prefix":"10.1515","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5424-579X","authenticated-orcid":false,"given":"Alice","family":"Brochier","sequence":"first","affiliation":[{"name":"Hematology Department of Laboratory Medicine , Saint-Luc University Hospital , Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Mairesse","sequence":"additional","affiliation":[{"name":"Hematology Department of Laboratory Medicine , Saint-Luc University Hospital , Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Saussoy","sequence":"additional","affiliation":[{"name":"Hematology Department of Laboratory Medicine , Saint-Luc University Hospital , Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christel","family":"Gavard","sequence":"additional","affiliation":[{"name":"Hematology Department of Laboratory Medicine , Saint-Luc University Hospital , Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Desmet","sequence":"additional","affiliation":[{"name":"Hematology Department of Laboratory Medicine , Saint-Luc University Hospital , Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9dric","family":"Hermans","sequence":"additional","affiliation":[{"name":"Hemostasis and Thrombosis Unit\/Hemophilia Treatment Centre\/Division of Hematology , Saint-Luc University Hospital , Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Gruson","sequence":"additional","affiliation":[{"name":"Biochemistry Department of Laboratory Medicine , Saint-Luc University Hospital , Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Astrid","family":"van Dievoet","sequence":"additional","affiliation":[{"name":"Hematology Department of Laboratory Medicine , Saint-Luc University Hospital , Brussels , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"2023033112140910401_j_cclm-2022-0377_ref_001","doi-asserted-by":"crossref","unstructured":"Fraser, CG, Harris, EK. Generation and application of data on biological variation in clinical chemistry. Crit Rev Clin Lab Sci 1989;27:409\u201337. https:\/\/doi.org\/10.3109\/10408368909106595.","DOI":"10.3109\/10408368909106595"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_002","doi-asserted-by":"crossref","unstructured":"Fraser, CG. Biological variation: a rapidly evolving aspect of laboratory medicine. J Lab Precis Med 2017;2:35\u20135. https:\/\/doi.org\/10.21037\/jlpm.2017.06.09.","DOI":"10.21037\/jlpm.2017.06.09"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_003","doi-asserted-by":"crossref","unstructured":"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\u20135. https:\/\/doi.org\/10.1515\/cclm-2015-0067.","DOI":"10.1515\/cclm-2015-0067"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_004","doi-asserted-by":"crossref","unstructured":"Bartlett, WA, Braga, F, Carobene, A, Co\u015fkun, 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\u201385. https:\/\/doi.org\/10.1515\/cclm-2014-1127.","DOI":"10.1515\/cclm-2014-1127"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_005","doi-asserted-by":"crossref","unstructured":"Aarsand, AK, R\u00f8raas, T, Fernandez-Calle, P, Ricos, C, D\u00edaz-Garz\u00f3n, 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\u201314. https:\/\/doi.org\/10.1373\/clinchem.2017.281808.","DOI":"10.1373\/clinchem.2017.281808"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_006","doi-asserted-by":"crossref","unstructured":"Connors, JM. Thrombophilia testing and venous thrombosis. N Engl J Med 2017;377:1177\u201387. https:\/\/doi.org\/10.1056\/nejmra1700365.","DOI":"10.1056\/NEJMra1700365"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_007","doi-asserted-by":"crossref","unstructured":"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\u20137. https:\/\/doi.org\/10.1111\/ijlh.13388.","DOI":"10.1111\/ijlh.13388"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_008","doi-asserted-by":"crossref","unstructured":"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\u201325. https:\/\/doi.org\/10.3109\/10408363.2016.1150252.","DOI":"10.3109\/10408363.2016.1150252"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_009","doi-asserted-by":"crossref","unstructured":"Ric\u00f3s 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\u20139. https:\/\/doi.org\/10.11613\/bm.2009.023.","DOI":"10.11613\/BM.2009.023"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_010","doi-asserted-by":"crossref","unstructured":"Carobene, A, Strollo, M, Jonker, N, Barla, G, Bartlett, WA, Sandberg, S, et al.. Sample collections from healthy volunteers for biological variation estimates\u2019 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\u2013608. https:\/\/doi.org\/10.1515\/cclm-2016-0035.","DOI":"10.1515\/cclm-2016-0035"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_011","unstructured":"Institute, CALS. Procedures for the collection of diagnostic blood specimens by venipuncture; Approved standard-sixth edition; 2007."},{"key":"2023033112140910401_j_cclm-2022-0377_ref_012","doi-asserted-by":"crossref","unstructured":"Woodhams, B, Girardot, O, Blanco, MJ, Colesse, G, Gourmelin, Y. Stability of coagulation proteins in frozen plasma. Blood Coagul Fibrinolysis 2001;12:229\u201336. https:\/\/doi.org\/10.1097\/00001721-200106000-00002.","DOI":"10.1097\/00001721-200106000-00002"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_013","doi-asserted-by":"crossref","unstructured":"Ceriotti, F, D\u00edaz-Garz\u00f3n Marco, J, Fern\u00e1ndez-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\u20137. https:\/\/doi.org\/10.1515\/cclm-2019-1182.","DOI":"10.1515\/cclm-2019-1182"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_014","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Calle, P, D\u00edaz-Garz\u00f3n, 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\u201393. https:\/\/doi.org\/10.1515\/cclm-2021-0904.","DOI":"10.1515\/cclm-2021-0904"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_015","doi-asserted-by":"crossref","unstructured":"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\u201312. https:\/\/doi.org\/10.1177\/000456329703400103.","DOI":"10.1177\/000456329703400103"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_016","doi-asserted-by":"crossref","unstructured":"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\u201346. https:\/\/doi.org\/10.1373\/clinchem.2016.261248.","DOI":"10.1373\/clinchem.2016.261248"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_017","doi-asserted-by":"crossref","unstructured":"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\u201341. https:\/\/doi.org\/10.1055\/s-0034-1543994.","DOI":"10.1055\/s-0034-1543994"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_018","doi-asserted-by":"crossref","unstructured":"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\u201333. https:\/\/doi.org\/10.1016\/1047-2797(92)90017-k.","DOI":"10.1016\/1047-2797(92)90017-K"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_019","doi-asserted-by":"crossref","unstructured":"Melzi d\u2019Eril, 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\u201360.","DOI":"10.1515\/cclm.1997.35.4.257"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_020","doi-asserted-by":"crossref","unstructured":"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\u201383. https:\/\/doi.org\/10.1515\/cclm.2004.015.","DOI":"10.1515\/CCLM.2004.015"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_021","doi-asserted-by":"crossref","unstructured":"Aarsand, AK, Kristoffersen, AH, Sandberg, S, St\u00f8ve, B, Co\u015fkun, 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\u201370. https:\/\/doi.org\/10.1093\/clinchem\/hvab100.","DOI":"10.1093\/clinchem\/hvab100"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_022","unstructured":"Westgard, QC; 2019. Available from: https:\/\/www.westgard.com\/biodatabase1.htm [accessed on 28 February 2022]."},{"key":"2023033112140910401_j_cclm-2022-0377_ref_023","doi-asserted-by":"crossref","unstructured":"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\u20133. https:\/\/doi.org\/10.1111\/jth.14315.","DOI":"10.1111\/jth.14315"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_024","doi-asserted-by":"crossref","unstructured":"Walton, RM. Subject-based reference values: biological variation, individuality, and reference change values. Vet Clin Pathol 2012;41:175\u201381. https:\/\/doi.org\/10.1111\/j.1939-165x.2012.00414.x.","DOI":"10.1111\/j.1939-165X.2012.00414.x"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_025","unstructured":"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\u201344."},{"key":"2023033112140910401_j_cclm-2022-0377_ref_026","doi-asserted-by":"crossref","unstructured":"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\u201336. https:\/\/doi.org\/10.3748\/wjg.v12.i48.7725.","DOI":"10.3748\/wjg.v12.i48.7725"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_027","doi-asserted-by":"crossref","unstructured":"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\u20136. https:\/\/doi.org\/10.1016\/j.jhep.2004.09.009.","DOI":"10.1016\/j.jhep.2004.09.009"},{"key":"2023033112140910401_j_cclm-2022-0377_ref_028","doi-asserted-by":"crossref","unstructured":"Montagnana, M, Salvagno, GL, Lippi, G. Circadian variation within hemostasis: an underrecognized link between biology and disease? Semin Thromb Hemost 2009;35:23\u201333. https:\/\/doi.org\/10.1055\/s-0029-1214145.","DOI":"10.1055\/s-0029-1214145"}],"container-title":["Clinical Chemistry and Laboratory Medicine (CCLM)"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cclm-2022-0377\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cclm-2022-0377\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T16:39:23Z","timestamp":1680280763000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cclm-2022-0377\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,27]]},"references-count":28,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,6,22]]},"published-print":{"date-parts":[[2022,8,26]]}},"alternative-id":["10.1515\/cclm-2022-0377"],"URL":"https:\/\/doi.org\/10.1515\/cclm-2022-0377","relation":{},"ISSN":["1434-6621","1437-4331"],"issn-type":[{"value":"1434-6621","type":"print"},{"value":"1437-4331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,27]]}}}