{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:44:30Z","timestamp":1792071870144,"version":"4.4.0"},"reference-count":17,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hereditary factor X (FX) deficiency is a rare autosomal recessive bleeding disorder for which individualized pharmacokinetic (PK) assessment can support optimized prophylactic management. The WAPPS\u2010Hemo platform enables population pharmacokinetic (PopPK) individualized PK predictions based on sparse sampling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To develop and evaluate a PopPK model for Coagdex, a FX concentrate, using manufacturer\u2010provided PK data for its implementation on the WAPPS\u2010Hemo platform.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Model development followed the standard PopPK modelling approach (structural, compartmental and variance partitioning steps and goodness of fit assessments). Covariates tested were age, body weight, height, fat\u2010free mass, sex and assay type. Predictive evaluation was performed through Visual Predictive Checks (pcVPC) and Limited Sampling Analysis (LSA). LSA strategies were evaluated using dosing and sampling scenarios consistent with recommended treatment regimens for plasma\u2011derived FX (pdFX) concentrate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A two\u2010compartment model accounting for between\u2010occasion and between\u2010subject variability with fat\u2010free mass and assay\u2010type as main covariates was selected. Evaluation showed good predictive capabilities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We have developed a PopPK model to support WAPPS\u2010Hemo individualized prophylaxis in FX deficiency using sparse PK data. Prospective PK data collected through the WAPPS\u2011Hemo database will be used to further characterize Factor X PK and enhance patient care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hae.70420","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:56:27Z","timestamp":1791820587000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetics of Plasma\u2011Derived Factor X Using Clotting and Chromogenic Assays: A WAPPS\u2011Hemo Model"],"prefix":"10.1111","author":[{"given":"Dagmar M.","family":"Hajducek","sequence":"first","affiliation":[{"name":"School of Pharmacy University of Waterloo  Waterloo Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Chelle","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Waterloo  Waterloo Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Scarpellini","sequence":"additional","affiliation":[{"name":"Kedrion SpA, Barga  Lucca Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Edginton","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Waterloo  Waterloo Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Iorio","sequence":"additional","affiliation":[{"name":"Department of Health Research Methods Evidence and Impact Mcmaster University  Hamilton Ontario Canada"},{"name":"Department of Medicine McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.blre.2021.100833","article-title":"Diagnosis, Therapeutic Advances, and Key Recommendations for the Management of Factor X Deficiency","volume":"50","author":"Peyvandi F.","year":"2021","journal-title":"Blood Reviews"},{"issue":"3","key":"e_1_2_13_3_1","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1111\/bjh.13058","article-title":"Guideline for the Diagnosis and Management of the Rare Coagulation Disorders: A United Kingdom Haemophilia Centre Doctors' Organization Guideline on Behalf of the British Committee for Standards in Haematology","volume":"167","author":"Mumford A. D.","year":"2014","journal-title":"British Journal of Haematology"},{"issue":"3","key":"e_1_2_13_4_1","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1111\/hae.12894","article-title":"Pharmacokinetics of a High\u2010Purity Plasma\u2010Derived Factor X Concentrate in Subjects With Moderate or Severe Hereditary Factor X Deficiency","volume":"22","author":"Austin S.","year":"2016","journal-title":"Haemophilia"},{"issue":"6","key":"e_1_2_13_5_1","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1111\/hae.13500","article-title":"Prophylactic Treatment of Bleeding Episodes in Children <12 Years With Moderate to Severe Hereditary Factor X Deficiency (FXD): Efficacy and Safety of a High\u2010Purity Plasma\u2010Derived Factor X (pdFX) Concentrate","volume":"24","author":"Liesner R.","year":"2018","journal-title":"Haemophilia"},{"issue":"1","key":"e_1_2_13_6_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/hae.14894","article-title":"Plasma\u2010Derived Human Factor X Concentrate for the Treatment of Patients With Hereditary Factor X Deficiency","volume":"30","author":"Escobar M.","year":"2023","journal-title":"Haemophilia"},{"issue":"3","key":"e_1_2_13_7_1","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1111\/hae.12893","article-title":"Efficacy, Safety and Pharmacokinetics of a New High\u2010Purity Factor X Concentrate in Subjects With Hereditary Factor X Deficiency","volume":"22","author":"Austin S.","year":"2016","journal-title":"Haemophilia"},{"key":"e_1_2_13_8_1","unstructured":"B. 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(BPL) \u201cCOAGADEX (Coagulation Factor X [Human]) Package Insert \u201d (Bio Products Laboratory Ltd 2023)."},{"issue":"4","key":"e_1_2_13_9_1","doi-asserted-by":"crossref","DOI":"10.2196\/resprot.6558","article-title":"Development of a Web\u2010Accessible Population Pharmacokinetic Service\u2014Hemophilia (WAPPS\u2010Hemo): Study Protocol","volume":"5","author":"Iorio A.","year":"2016","journal-title":"JMIR Research Protocols"},{"issue":"4","key":"e_1_2_13_10_1","doi-asserted-by":"crossref","DOI":"10.2196\/resprot.6559","article-title":"Data Analysis Protocol for the Development and Evaluation of Population Pharmacokinetic Models for Incorporation Into the Web\u2010Accessible Population Pharmacokinetic Service\u2014Hemophilia (WAPPS\u2010HEMO)","volume":"5","author":"McEneny\u2010King A.","year":"2016","journal-title":"JMIR Research Protocols"},{"issue":"3","key":"e_1_2_13_11_1","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1111\/hae.13977","article-title":"Development and Evaluation of the Population Pharmacokinetic Models for FVIII and FIX Concentrates of the WAPPS\u2010Hemo Project","volume":"26","author":"Hajducek D. M.","year":"2020","journal-title":"Haemophilia"},{"issue":"4","key":"e_1_2_13_12_1","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1111\/hae.15027","article-title":"Development of a Plasminogen Population PK Model Supporting Prophylactic Replacement Therapy for Plasminogen Defficient Patients Within WAPPS\u2010Hemo Platform","volume":"30","author":"Chelle P.","year":"2024","journal-title":"Haemophilia"},{"key":"e_1_2_13_13_1","unstructured":"C. f. D. C. a. Prevention and N. C. f. H. Statistics \u201cNational Health and Nutrition Examination Survey Data \u201dU.S. Department of Health and Human Services Centers for Disease Control and Prevention Hyattsville MD 2023."},{"issue":"5","key":"e_1_2_13_14_1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1023\/A:1012299115260","article-title":"Ways to Fit a PK Model With Some Data Below the Quantification Limit","volume":"28","author":"Beal S.","year":"2001","journal-title":"Journal of Pharmacokinetics and Pharmacodynamics"},{"key":"e_1_2_13_15_1","unstructured":"S. G.WichaandS.Hennig \u201cHandling Inter\u2010Occasion Variability in Model Implementation for Bayesian Forecasting: A Comparison of Methods and Metrics \u201d inAnnual Meeting of the Population Approach Group in Europe Montreux Switzerland(2018)."},{"issue":"11","key":"e_1_2_13_16_1","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1007\/s40262-015-0277-z","article-title":"Prediction of Fat\u2010Free Mass in Children","volume":"54","author":"Al\u2010Sallami H. S.","year":"2015","journal-title":"Clinical Pharmacokinetics"},{"issue":"2","key":"e_1_2_13_17_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1208\/s12248-011-9255-z","article-title":"Prediction\u2010Corrected Visual Predictive Checks for Diagnosing Nonlinear Mixed\u2010Effects Models","volume":"13","author":"Bergstrand M.","year":"2011","journal-title":"Aaps Journal"},{"issue":"4","key":"e_1_2_13_18_1","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1111\/jth.13271","article-title":"Population Pharmacokinetics of Plasma\u2010Derived Factor IX: Procedures for Dose Individualization","volume":"14","author":"Brekkan A.","year":"2016","journal-title":"Journal of Thrombosis and Haemostasis"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.70420","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hae.70420","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.70420","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:47:51Z","timestamp":1792068471000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.70420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,12]]},"references-count":17,"alternative-id":["10.1111\/hae.70420"],"URL":"https:\/\/doi.org\/10.1111\/hae.70420","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,12]]},"assertion":[{"value":"2026-06-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"hae.70420"}}