{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:27:20Z","timestamp":1786685240608,"version":"build-2736575974"},"reference-count":62,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"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>Introduction<\/jats:title>\n                    <jats:p>The severity of haemophilia A is classified by the degree of factor VIII (FVIII) deficiency, rather than by clinical manifestations. However, FVIII activity alone does not necessarily accurately reflect clinical severity such as bleeding tendency, and patients with mild\u2010to\u2010moderate haemophilia A can experience significant disease burden.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This narrative review explores the clinical relevance of non\u2010severe haemophilia A (focusing on moderate disease), and examines the profile of patients with, and the evidence supporting the use of prophylaxis to manage, this disease form.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A PubMed search was conducted (no language\/date limits), using terms including \u2018hemophilia\u2019 or \u2018haemophilia\u2019, and \u2018moderate\u2019, \u2018nonsevere\u2019 or \u2018non\u2010severe\u2019, with the names of prophylactic agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Some patients with moderate haemophilia A experience significant disease burden (in terms of bleeding frequency and joint damage), diminished health\u2010related quality of life and marked economic impact. In addition, variation in bleeding phenotype across disease severity levels has been recognised, such that patients with moderate disease may have a severe phenotype and experience more frequent spontaneous bleeds than those with a mild phenotype. Few studies have specifically assessed outcomes associated with prophylaxis in patients with moderate haemophilia A. However, available data suggest that prophylaxis with FVIII concentrates and non\u2010factor treatments (i.e. emicizumab) provides beneficial effects in terms of bleeding frequency and joint health.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Severity classification alone is insufficient to predict bleeding tendency, and joint bleeding and joint injury are observed in patients with moderate disease. As such, routine prophylaxis may be recommended for some patients with moderate haemophilia A.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hae.70364","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:42:33Z","timestamp":1786682553000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Current State of Moderate Congenital Haemophilia A and the Need for Preventive Treatment"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9348-9815","authenticated-orcid":false,"given":"Masahiro","family":"Takeyama","sequence":"first","affiliation":[{"name":"Division of Hemophilia National Hospital Organization Osaka National Hospital Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6844-5725","authenticated-orcid":false,"given":"Atsuki","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Pediatrics St. Marianna University School of Medicine Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8110-4201","authenticated-orcid":false,"given":"Tomoko","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Blood Coagulation Ogikubo Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Ito","sequence":"additional","affiliation":[{"name":"Medical Affairs Division Chugai Pharmaceutical Co., Ltd Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yui","family":"Sugawara","sequence":"additional","affiliation":[{"name":"Medical Affairs Division Chugai Pharmaceutical Co., Ltd Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Ioka","sequence":"additional","affiliation":[{"name":"Medical Affairs Division Chugai Pharmaceutical Co., Ltd Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9779-5361","authenticated-orcid":false,"given":"Tazuko","family":"Tokugawa","sequence":"additional","affiliation":[{"name":"Division of Hematology Hyogo Medical University Hospital Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"World Federation of Hematology.Hemophilia.2020. Accessed 22 August 2025https:\/\/elearning.wfh.org\/elearning\u2010centres\/hemophilia\/."},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.7326\/M19-1208"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1615621"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rpth.2023.102264"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/rth2.12825"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15676"},{"key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1055\/s-0033-1354422","article-title":"Arthropathy in Patients With Moderate Hemophilia A: A Systematic Review of the Literature","volume":"39","author":"Di Minno M. N.","year":"2013","journal-title":"Seminars in Thrombosis and Hemostasis"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2023.09.029"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11071969"},{"key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1016\/j.jtha.2024.05.030","article-title":"Bleeding Phenotype According to Factor Level in 825 Children With Nonsevere Hemophilia: Data From the Pednet Cohort","volume":"22","author":"Kovel M. S.","year":"2024","journal-title":"Journal of Thrombosis and Haemostasis"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023011366"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007620"},{"key":"e_1_2_11_14_1","first-page":"s330","article-title":"Outcome in Moderate Haemophilia","volume":"12","author":"Uijl I.","year":"2014","journal-title":"Blood Transfus"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rpth.2023.100098"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2008.01781.x"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2006.01730.x"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2010.02383.x"},{"key":"e_1_2_11_19_1","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s13023-022-02301-0","article-title":"Health\u2010Related Quality of Life, Direct Medical and Societal Costs Among Children With Moderate or Severe Haemophilia in Europe: Multivariable Models of the Chess\u2010Paeds Study","volume":"17","author":"Rodriguez\u2010Santana I.","year":"2022","journal-title":"Orphanet journal of rare diseases"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13616"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rpth.2025.102737"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13693"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14251"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14871"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-024-02956-0"},{"key":"e_1_2_11_26_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s13023-022-02300-1","article-title":"Differential Humanistic and Economic Burden of Mild, Moderate and Severe Haemophilia in European Adults: A Regression Analysis of the Chess Ii Study","volume":"17","author":"Rodriguez\u2010Santana I.","year":"2022","journal-title":"Orphanet journal of rare diseases"},{"key":"e_1_2_11_27_1","unstructured":"Ministry of Health\u201cLabour and Welfare (MHLW) \u201d inResearch Project on QOL in Patients With Haemophilia: FY2023 Survey Report(2024) https:\/\/hemqol2022.acsurvey.jp\/result\/(inJapanese)."},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14766"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13111"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14046"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2024.05.026"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.15110"},{"key":"e_1_2_11_33_1","first-page":"206","article-title":"Expert Opinion for Defining a Severe Bleeding Phenotype to Guide Prophylaxis in Patients with Nonsevere Hemophilia","volume":"46","author":"Pfrepper C.","year":"2026","journal-title":"Hamostaseologie"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14201"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13215"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14866"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14934"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2020.1775576"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02539.x"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12041368"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14676"},{"key":"e_1_2_11_42_1","doi-asserted-by":"crossref","first-page":"e181","DOI":"10.1055\/s-0044-1785524","article-title":"Disease Burden, Clinical Outcomes, and Quality of Life in People With Hemophilia a Without Inhibitors in Europe: Analyses From Chess Ii\/Chess Paeds","volume":"8","author":"Chowdary P.","year":"2024","journal-title":"TH Open"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14636"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/MBC.0000000000000825"},{"key":"e_1_2_11_45_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.rpth.2024.102355","article-title":"Arthropathy on X\u2010Rays in 363 Persons With Hemophilia: Long\u2010Term Development, and Impact of Birth Cohort and Inhibitor Status","volume":"8","author":"Heel D. A. M.","year":"2024","journal-title":"Res Pract Thromb Haemost"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-1175-6530"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s41669-024-00540-4"},{"key":"e_1_2_11_48_1","first-page":"479","article-title":"Factor Viii Replacement Is Still the Standard of Care in Haemophilia A","volume":"17","author":"Aledort L.","year":"2019","journal-title":"Blood Transfus"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.14381"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-02-483263"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rpth.2025.102887"},{"key":"e_1_2_11_52_1","unstructured":"Sobi.Altuvoct (Efanesoctocog Alfa)\u2014Prescribing Information2025. Accessed 28 August 2025https:\/\/pro.sobi.com\/system\/files\/Altuvoct%20PI%20IE%20%28Oct%202024%29.pdf."},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2023.101164"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH07-12-0724"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1177\/20406207231218624"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.13420"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.13876"},{"key":"e_1_2_11_58_1","doi-asserted-by":"crossref","first-page":"3001","DOI":"10.2147\/PPA.S394216","article-title":"Real\u2010World Experience of People With Hemophilia a Receiving Turoctocog Alfa Pegol (N8\u2010Gp): Results From a Patient Experience Survey","volume":"17","author":"Eichler H.","year":"2023","journal-title":"Patient Prefer Adherence"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0042-1756188"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.14114"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(22)00377-5"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.70070"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/jha2.832"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.70364","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hae.70364","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.70364","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:42:43Z","timestamp":1786682563000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.70364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,13]]},"references-count":62,"alternative-id":["10.1111\/hae.70364"],"URL":"https:\/\/doi.org\/10.1111\/hae.70364","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,13]]},"assertion":[{"value":"2025-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"hae.70364"}}