{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:23:36Z","timestamp":1793053416169,"version":"4.5.0"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Patients with hemophilia require lifelong treatment, but the real-world lifetime economic burden of hemophilia remains unclear. This study aims to estimate the lifetime economic burden of hemophilia using real-world data, accounting for cost variation by disease phase and over time.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Male patients with hemophilia A (PwHa) or B (PwHb) recorded in South Korea\u2019s Health Insurance Review and Assessment (HIRA) database from 2007 to 2022 were included. Survival was estimated using the rolling extrapolation method. A phase-specific costing approach was applied, distinguishing three phases: before hemophilic arthropathy (BH), after hemophilic arthropathy (AH), and 1 year before death (BD). Transition probabilities from BH to AH were calculated based on incidence rates of hemophilic arthropathy. Phase-specific annual costs were modeled using generalized estimating equations (GEEs), and predicted costs were multiplied by phase-specific probabilities from birth to estimated life expectancy to derive lifetime costs.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Estimated life expectancy for PwHa (n\u2009=\u20092,624) and PwHb (n\u2009=\u2009664) in South Korea between 2007\u22122022 was 76.13 and 77.54 years, respectively. The incidence rate of hemophilic arthropathy was 0.090 cases\/person-year [95% confidence interval, 0.084\u20130.097] for PwHa and 0.080 [0.070\u20130.092] for PwHb, yielding transition probabilities from BH to AH of 0.086 (PwHa) and 0.077 (PwHb). Mean annual costs were highest in the BD phase, followed by AH and BH phases: PwHa (BH: $11,331; AH: $27,271; BD: $27,985); PwHb (BH: $15,567; AH: $38,659; BD: $55,985). Compared to PwHa, PwHb incurred 1.37 and 1.42 times higher BH and AH costs, respectively (p\u2009&lt;\u20090.05). Estimated lifetime cost was 1.76 times higher for PwHb ($22.25 million) than PwHa ($12.62 million) in hypothetical patients born in 2000.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Hemophilia imposes a substantial economic burden across the lifespan, with PwHb incurring higher lifetime costs than PwHa. These real-world estimates can support more informed resource allocation and planning for hemophilia care.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0333683","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T17:24:46Z","timestamp":1759771486000},"page":"e0333683","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Lifetime economic burden of hemophilia using a nationwide real-world healthcare data"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9705-240X","authenticated-orcid":true,"given":"Joo-Young","family":"Byun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hoon","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suk-Chan","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamin","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8481-5503","authenticated-orcid":true,"given":"Mihai","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0601-7754","authenticated-orcid":true,"given":"Eui-Kyung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"key":"pone.0333683.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/hae.14046","article-title":"WFH Guidelines for the Management of Hemophilia, 3rd edition","author":"A Srivastava","year":"2020","journal-title":"Haemophilia"},{"issue":"9","key":"pone.0333683.ref002","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1111\/jth.15444","article-title":"Hemophilic arthropathy: Current knowledge and future perspectives","volume":"19","author":"R Gualtierotti","year":"2021","journal-title":"J Thromb Haemost"},{"issue":"8","key":"pone.0333683.ref003","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1016\/j.jval.2017.04.017","article-title":"Economic Burden of Illness among Persons with Hemophilia B from HUGS Vb: Examining the Association of Severity and Treatment Regimens with Costs and Annual Bleed Rates","volume":"20","author":"CX Chen","year":"2017","journal-title":"Value Health"},{"key":"pone.0333683.ref004","doi-asserted-by":"crossref","first-page":"51","DOI":"10.15256\/joc.2011.1.2","article-title":"Haemophilia and joint disease: pathophysiology, evaluation, and management","volume":"1","author":"K Knobe","year":"2011","journal-title":"J Comorb"},{"key":"pone.0333683.ref005","doi-asserted-by":"crossref","first-page":"100912","DOI":"10.1016\/j.blre.2021.100912","article-title":"Clinical burden of hemophilia in older adults: Beyond bleeding risk","volume":"53","author":"MH Hodroj","year":"2022","journal-title":"Blood Rev"},{"issue":"7","key":"pone.0333683.ref006","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1182\/blood.V99.7.2337","article-title":"The effects of postponing prophylactic treatment on long-term outcome in patients with severe hemophilia","volume":"99","author":"K Fischer","year":"2002","journal-title":"Blood"},{"issue":"4","key":"pone.0333683.ref007","first-page":"494","article-title":"Factor VIII half-life and clinical phenotype of severe hemophilia A","volume":"90","author":"K van Dijk","year":"2005","journal-title":"Haematologica"},{"key":"pone.0333683.ref008","unstructured":"Mayo Clinic. 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Castaman","year":"2019","journal-title":"Haematologica"},{"issue":"2","key":"pone.0333683.ref019","doi-asserted-by":"crossref","first-page":"419","DOI":"10.2307\/2533947","article-title":"Estimating medical costs from incomplete follow-up data","volume":"53","author":"DY Lin","year":"1997","journal-title":"Biometrics"},{"key":"pone.0333683.ref020","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1093\/biomet\/87.2.329","article-title":"Estimating medical costs with censored data","volume":"87","author":"H Bang","year":"2000","journal-title":"Biometrika"},{"issue":"13","key":"pone.0333683.ref021","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1002\/(SICI)1097-0258(19990715)18:13<1627::AID-SIM159>3.0.CO;2-D","article-title":"Monte Carlo estimation of extrapolation of quality-adjusted survival for follow-up studies","volume":"18","author":"JS Hwang","year":"1999","journal-title":"Stat Med"},{"issue":"12","key":"pone.0333683.ref022","article-title":"Estimating lifetime medical costs from censored claims data","volume":"26","author":"J-S Hwang","year":"2017","journal-title":"Health Econ"},{"key":"pone.0333683.ref023","doi-asserted-by":"crossref","first-page":"145","DOI":"10.2147\/CEOR.S31552","article-title":"Techniques for estimating health care costs with censored data: an overview for the health services researcher","volume":"4","author":"HC Wijeysundera","year":"2012","journal-title":"Clinicoecon Outcomes Res"},{"key":"pone.0333683.ref024","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.thromres.2024.03.029","article-title":"Clinical and economic burden of immune tolerance induction in entire patients with hemophilia A: Insights from a real-world Korean setting","volume":"237","author":"A-Y Kim","year":"2024","journal-title":"Thromb Res"},{"issue":"7","key":"pone.0333683.ref025","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1177\/0272989X17696997","article-title":"A Procedure for Deriving Formulas to Convert 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Study Using Nationwide Claims Data of South Korea","volume":"40","author":"J-Y Byun","year":"2023","journal-title":"Adv Ther"},{"issue":"10","key":"pone.0333683.ref030","first-page":"818","article-title":"Regional Variation in Standardized Costs of Care at Children\u2019s Hospitals","volume":"12","author":"JA Jonas","year":"2017","journal-title":"J Hosp Med"},{"issue":"1","key":"pone.0333683.ref031","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s41043-019-0195-z","article-title":"Determinants of health seeking behavior for chronic non-communicable diseases and related out-of-pocket expenditure: results from a cross-sectional survey in northern Bangladesh","volume":"38","author":"FB Rasul","year":"2019","journal-title":"J Health Popul Nutr"},{"key":"pone.0333683.ref032","volume-title":"Lifetime healthcare costs W100 mil","author":"R Kim","year":"2012"},{"issue":"3","key":"pone.0333683.ref033","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1111\/jth.15182","article-title":"Mortality, life expectancy, and causes of death of persons with hemophilia in the Netherlands 2001-2018","volume":"19","author":"S Hassan","year":"2021","journal-title":"J Thromb Haemost"},{"issue":"6","key":"pone.0333683.ref034","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1111\/hae.14636","article-title":"Long-term joint outcomes in adolescents with moderate or severe haemophilia A","volume":"28","author":"DE Schmidt","year":"2022","journal-title":"Haemophilia"},{"issue":"3","key":"pone.0333683.ref035","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1111\/j.1365-2516.2010.02450.x","article-title":"Trends in bleeding patterns during prophylaxis for severe haemophilia: observations from a series of prospective clinical trials","volume":"17","author":"K Fischer","year":"2011","journal-title":"Haemophilia"},{"issue":"13","key":"pone.0333683.ref036","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1182\/blood-2015-01-528414","article-title":"Optimal treatment strategies for hemophilia: achievements and limitations of current prophylactic regimens","volume":"125","author":"J Oldenburg","year":"2015","journal-title":"Blood"},{"key":"pone.0333683.ref037","doi-asserted-by":"crossref","first-page":"207","DOI":"10.2147\/JBM.S50644","article-title":"Optimal management of hemophilic arthropathy and hematomas","volume":"5","author":"S Lobet","year":"2014","journal-title":"J Blood Med"},{"issue":"1","key":"pone.0333683.ref038","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40122-021-00345-x","article-title":"Current and Emerging Approaches for Pain Management in Hemophilic Arthropathy","volume":"11","author":"R Gualtierotti","year":"2022","journal-title":"Pain 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