{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:38:25Z","timestamp":1792654705143,"version":"4.5.0"},"reference-count":11,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000165","name":"Sick Kids Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000165","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2025,5]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Laboratory reagents impact measured factor activity of extended half\u2010life (EHL) concentrates. Variability in measurements may lead to under or over estimation of the pharmacokinetic (PK) parameters, and thus influence clinical dosing decisions. Since 2020, WAPPS\u2010Hemo (\n www.wapps\u2010hemo.org<\/jats:ext-link>\n ) has been collecting reagent information when haemophilia centres submit data for PK parameters estimation.\n <\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To identify the pairs of concentrates (recombinant FVIII and FIX) and reagents leading to significant discrepancies between observed PK estimates compared to WAPPS\u2010Hemo population.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n PK data were extracted from the WAPPS\u2010Hemo database. PK estimates were obtained using WAPPS\u2010Hemo Bayesian engine and analysis was reported for terminal half\u2010life and time to 3% following a 50\u00a0IU\/kg infusion. Log\u2010deviations between individual PK estimates and WAPPS\u2010Hemo population PK models typical values were calculated to remove known sources of variability. Multivariate analysis of variance (MANOVA) regression was performed to assess the reagent effects.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 3853 and 1312 PK estimates were used to analyse reagent effects on the four FVIII and three FIX EHL concentrates, respectively. The reagent was not provided for 2391 PK estimates (46.3%). WFH unadvised reagents were provided for 78 PK estimates only (2.8% of known reagents). For each concentrate\/reagent pair recommended by WFH, no significant difference was identified, except for rFIX\u2010Fc whose PK parameters were significantly and clinically under\u2010estimated by STA PTT\u2010A.<\/jats:p>\n <\/jats:sec>\n \n Discussion\/Conclusion<\/jats:title>\n Real\u2010world data provided by haemophilia centres showed high congruence with WFH guidelines, although its sizable number not declaring reagent. WFH\u2010recommended reagents did not significantly impact PK estimation. For rFVIII\u2010PEG, reagents also did not impact PK estimation. Although usually not enough data were available to assess reagents that were unadvised by WFH.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/hae.70021","type":"journal-article","created":{"date-parts":[[2025,3,9]],"date-time":"2025-03-09T23:07:58Z","timestamp":1741561678000},"page":"557-565","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Impact of Laboratory Reagents on Pharmacokinetic Profiling"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0167-4774","authenticated-orcid":false,"given":"Pierre","family":"Chelle","sequence":"first","affiliation":[{"name":"School of Pharmacy University of Waterloo Waterloo Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Hajducek","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Waterloo Waterloo Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Iserman","sequence":"additional","affiliation":[{"name":"Dept of Health Research Methods, Evidence and Impact and Dept of Medicine McMaster University Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3331-8766","authenticated-orcid":false,"given":"Alfonso","family":"Iorio","sequence":"additional","affiliation":[{"name":"Dept of Health Research Methods, Evidence and Impact and Dept of Medicine McMaster University Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9014-1653","authenticated-orcid":false,"given":"Andrea","family":"Edginton","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Waterloo Waterloo Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the International Prophylaxis Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0268-960X(03)00038-9"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0037-1963(03)80732-1"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/2040620718796429"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14394"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14784"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13012"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14046"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13977"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13001"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14784"},{"key":"e_1_2_8_12_1","first-page":"1","article-title":"Development and Evaluation of the Population Pharmacokinetic Models for FVIII and FIX Concentrates of the WAPPS\u2010Hemo Project","volume":"3","author":"Hajducek D.","year":"2020","journal-title":"Haemophilia"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.70021","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hae.70021","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.70021","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:52:19Z","timestamp":1792651939000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.70021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,7]]},"references-count":11,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1111\/hae.70021"],"URL":"https:\/\/doi.org\/10.1111\/hae.70021","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,7]]},"assertion":[{"value":"2024-06-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}