{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T12:07:52Z","timestamp":1776341272625,"version":"3.51.2"},"reference-count":38,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"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>Intracranial haemorrhage (ICH) is the most serious complication in infants and children with severe congenital bleeding disorders causing substantial mortality and long\u2010term neurological morbidity. The neonatal period carries the highest risk, particularly in severe haemophilia and rare factor deficiencies. We review the epidemiology, risk factors, prevention, recognition, management, and long\u2010term outcomes of ICH in children with congenital bleeding disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Current evidence from cohort studies, literature reviews, and recent clinical data addressing ICH in childhood is summarized, with attention to evolving prophylactic strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Neonatal ICH occurs in 2%\u20134% of infants with haemophilia and more frequently in severe FXIII and FX deficiency. Unrecognized bleeding disorders and traumatic delivery\u2014especially with forceps or vacuum\u2014substantially increase risk. Immediate factor replacement prior to diagnostic imaging improves survival and reduces neurological sequelae. After the neonatal period, risk remains elevated, particularly in children &lt;1 year not receiving prophylaxis. Early initiation of prophylaxis, historically limited by challenges with intravenous access, markedly reduces ICH incidence. Emerging non\u2010factor therapies (FVIII mimetics and rebalancing agents) enable earlier and more effective protection. Despite advances in care, 30%\u201440% of survivors experience long\u2010term neurological impairments with outcomes influenced by bleed location, cerebral shift, age at time of ICH, and treatment delays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ICH remains a major threat to children with severe bleeding disorders. Prevention requires early identification of at\u2010risk pregnancies, careful delivery planning, and timely diagnosis of bleeding disorders. Advances in prophylactic therapy offer the potential to significantly reduce ICH incidence and improve long\u2010term outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hae.70239","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T11:27:11Z","timestamp":1776338831000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prevention, Identification, Management and Long\u2010Term Complications of Intracranial Haemorrhage in Children With Haemophilia and Other Severe Bleeding Disorders\u2014A Practical Guidance"],"prefix":"10.1111","author":[{"given":"Manuel D.","family":"Carcao","sequence":"first","affiliation":[{"name":"Haemophilia Clinic and Haemostasis Program Division of Haematology\/Oncology Department of Paediatrics Hospital for Sick Children University of Toronto Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine G.","family":"Andersson","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Haemostasis and Department of Paediatric Haematology and Oncology Department of Clinical Sciences and Paediatrics Sk\u00e5ne University Hospital Lund University  Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Gouw","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology Amsterdam UMC Location University of Amsterdam  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"issue":"22","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.1182\/blood.2020009472","article-title":"Clinical Phenotype, Fibrinogen Supplementation, and Health\u2010Related Quality of Life in Patients With Afibrinogenemia","volume":"137","author":"Casini A.","year":"2021","journal-title":"Blood"},{"issue":"5","key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1007\/s00431-025-06126-4","article-title":"Glanzmann Thrombasthenia: A Multi\u2010Center Study of Demographics, Clinical Spectrum, and Treatment Efficacy","volume":"184","author":"Sherief L. M.","year":"2025","journal-title":"European Journal of Pediatrics"},{"issue":"4","key":"e_1_2_12_4_1","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1055\/s-0042-1756195","article-title":"Intracranial Hemorrhages in Neonates: Incidence, Risk Factors, and Treatment","volume":"49","author":"Andersson N. G.","year":"2023","journal-title":"Seminars in Thrombosis and Hemostasis"},{"issue":"2","key":"e_1_2_12_5_1","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1046\/j.1365-2141.1998.00806.x","article-title":"Congenital Factor X Deficiency: Spectrum of Bleeding Symptoms in 32 Iranian Patients","volume":"102","author":"Peyvandi F.","year":"1998","journal-title":"British Journal of Haematology"},{"issue":"4","key":"e_1_2_12_6_1","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1111\/hae.15033","article-title":"Severe Haemorrhages Leading to a Diagnosis of Rare Bleeding Disorder Occur at a Very Young Age: A Study From the FranceCoag Network","volume":"30","author":"Meunier S.","year":"2024","journal-title":"Haemophilia"},{"issue":"2","key":"e_1_2_12_7_1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/hae.13081","article-title":"Complications of Haemophilia in Babies (First Two Years of Life): A Report From the Centers for Disease Control and Prevention Universal Data Collection System","volume":"23","author":"Kulkarni R.","year":"2017","journal-title":"Haemophilia"},{"issue":"2","key":"e_1_2_12_8_1","doi-asserted-by":"crossref","first-page":"e101","DOI":"10.1111\/bjh.16740","article-title":"Long\u2010Term Follow\u2010Up of Neonatal Intracranial Haemorrhage in Children With Severe Haemophilia","volume":"190","author":"Andersson N. G.","year":"2020","journal-title":"British Journal of Haematology"},{"issue":"26","key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"2853","DOI":"10.1182\/blood.2021011849","article-title":"Incidence and Mortality Rates of Intracranial Hemorrhage in Hemophilia: A Systematic Review and Meta\u2010Analysis","volume":"138","author":"Zwagemaker A. F.","year":"2021","journal-title":"Blood"},{"issue":"5","key":"e_1_2_12_10_1","first-page":"378","article-title":"Intracranial Haemorrhage in Children and Adults With Haemophilia A and B: A Literature Review of the Last 20 Years","volume":"17","author":"Zanon E.","year":"2019","journal-title":"Blood Transfusion"},{"issue":"4","key":"e_1_2_12_11_1","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/hae.13461","article-title":"Intracranial Haemorrhage in Children With Inherited Bleeding Disorders in the UK 2003\u20132015: A National Cohort Study","volume":"24","author":"Chalmers E. A.","year":"2018","journal-title":"Haemophilia"},{"issue":"8","key":"e_1_2_12_12_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.rpth.2024.102607","article-title":"Risk Factors for Neurologic Sequelae in Children and Adolescents With Hemophilia After Intracranial Hemorrhage","volume":"8","author":"Evim M. S.","year":"2024","journal-title":"Research and Practice in Thrombosis and Haemostasis"},{"issue":"3","key":"e_1_2_12_13_1","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1055\/s-0041-1740566","article-title":"Risk and Management of Intracerebral Hemorrhage in Patients With Bleeding Disorders","volume":"48","author":"Dorgalaleh A.","year":"2022","journal-title":"Seminars in Thrombosis and Hemostasis"},{"issue":"3","key":"e_1_2_12_14_1","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1111\/j.1365-2141.2011.08967.x","article-title":"Neonatal Bleeding in Haemophilia: A European Cohort Study","volume":"156","author":"Richards M.","year":"2012","journal-title":"British Journal of Haematology"},{"issue":"10","key":"e_1_2_12_15_1","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.3324\/haematol.2018.209619","article-title":"Mode of Delivery in Hemophilia: Vaginal Delivery and Cesarean Section Carry Similar Risks for Intracranial Hemorrhages and Other Major Bleeds","volume":"104","author":"Andersson N. G.","year":"2019","journal-title":"Haematologica"},{"issue":"1","key":"e_1_2_12_16_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/hae.12726","article-title":"Mode of Delivery and Cranial Bleeding in Newborns With Haemophilia: A Systematic Review and Meta\u2010Analysis of the Literature","volume":"22","author":"Davies J.","year":"2016","journal-title":"Haemophilia"},{"issue":"6","key":"e_1_2_12_17_1","doi-asserted-by":"crossref","first-page":"E94","DOI":"10.1002\/ajh.24709","article-title":"Utility of Factor VIII and Factor VIII to von Willebrand Factor Ratio in Identifying 277 Unselected Carriers of Hemophilia A","volume":"92","author":"Labarque V.","year":"2017","journal-title":"American Journal of Hematology"},{"issue":"4","key":"e_1_2_12_18_1","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1111\/hae.15068","article-title":"Identifying Hemophilia B Carriers: Utility of aPTT, Factor IX Levels and Ratios of Factor IX to Other Vitamin K Dependent Factors","volume":"30","author":"Shu M.","year":"2024","journal-title":"Haemophilia"},{"issue":"4","key":"e_1_2_12_19_1","doi-asserted-by":"crossref","first-page":"538","DOI":"10.3324\/haematol.2012.074039","article-title":"Prophylaxis in Congenital Factor VII Deficiency: Indications, Efficacy and Safety. Results From the Seven Treatment Evaluation Registry (STER)","volume":"98","author":"Napolitano M.","year":"2013","journal-title":"Haematologica"},{"issue":"3","key":"e_1_2_12_20_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1055\/s-0037-1604109","article-title":"Intracranial Hemorrhage: A Devastating Outcome of Congenital Bleeding Disorders\u2010Prevalence, Diagnosis, and Management, With a Special Focus on Congenital Factor XIII Deficiency","volume":"44","author":"Alavi S. E. R.","year":"2018","journal-title":"Seminars in Thrombosis and Hemostasis"},{"issue":"2","key":"e_1_2_12_21_1","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1111\/hae.14738","article-title":"High Incidence of Intracranial Haemorrhage in Egyptian Children With Congenital Afibrinogenaemia","volume":"29","author":"Abdelwahab M.","year":"2023","journal-title":"Haemophilia"},{"issue":"4","key":"e_1_2_12_22_1","doi-asserted-by":"crossref","first-page":"914","DOI":"10.3324\/haematol.2024.285874","article-title":"Intracranial Hemorrhage Before Start of Prophylaxis in Children With Hemophilia: Incidence, Timing, and Potential for Prevention","volume":"110","author":"Andersson N. G.","year":"2025","journal-title":"Haematologica"},{"issue":"2","key":"e_1_2_12_23_1","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/bjh.14844","article-title":"Intracranial Haemorrhage in Children and Adolescents With Severe Haemophilia A or B\u2014The Impact of Prophylactic Treatment","volume":"179","author":"Andersson N. G.","year":"2017","journal-title":"British Journal of Haematology"},{"issue":"26","key":"e_1_2_12_24_1","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1182\/blood.2021013536","article-title":"Can We Do Something About ICH in Hemophilia?","volume":"138","author":"Young G.","year":"2021","journal-title":"Blood"},{"issue":"8","key":"e_1_2_12_25_1","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1055\/s-0039-1700521","article-title":"Use of Antithrombin Concentrate for Acquired Antithrombin Deficiency in Acutely Unwell Children Receiving Unfractionated Heparin","volume":"45","author":"Gaspar M.","year":"2019","journal-title":"Seminars in Thrombosis and Hemostasis"},{"issue":"3","key":"e_1_2_12_26_1","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1002\/pbc.22126","article-title":"The Clinical Management of Hemophilia and Head Trauma: A Survey of Current Clinical Practice Among Pediatric Hematology\/Oncology Physicians","volume":"53","author":"Witmer C. M.","year":"2009","journal-title":"Pediatric Blood & Cancer"},{"issue":"5","key":"e_1_2_12_27_1","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1111\/j.1365-2516.2007.01546.x","article-title":"Utility of Computed Tomography of the Head Following Head Trauma in Boys With Haemophilia","volume":"13","author":"Witmer C. M.","year":"2007","journal-title":"Haemophilia"},{"issue":"9","key":"e_1_2_12_28_1","doi-asserted-by":"crossref","DOI":"10.1002\/pbc.29811","article-title":"A Proposed Algorithm for Evaluation and Management of Pediatric Hemophilia Patients Who Present to the Emergency Department With Head Trauma","volume":"69","author":"Kracht M. J.","year":"2022","journal-title":"Pediatric Blood & Cancer"},{"issue":"3","key":"e_1_2_12_29_1","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.jtha.2022.10.004","article-title":"A Prospective, Multicenter, Open\u2010Label Phase III Study of Emicizumab Prophylaxis in Patients With Acquired Hemophilia A","volume":"21","author":"Shima M.","year":"2023","journal-title":"Journal of Thrombosis and Haemostasis"},{"issue":"6","key":"e_1_2_12_30_1","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1111\/hae.14177","article-title":"Effects of Emicizumab on APTT, FVIII Assays and FVIII Inhibitor Assays Using Different Reagents: Results of a UK NEQAS Proficiency Testing Exercise","volume":"26","author":"Lowe A.","year":"2020","journal-title":"Haemophilia"},{"issue":"2","key":"e_1_2_12_31_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.1365-2141.2010.08469.x","article-title":"Associations Between Intracranial Haemorrhage and Prescribed Prophylaxis in a Large Cohort of Haemophilia Patients in the United States","volume":"152","author":"Witmer C.","year":"2011","journal-title":"British Journal of Haematology"},{"issue":"1","key":"e_1_2_12_32_1","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1111\/j.1365-2516.2008.01815.x","article-title":"Long\u2010Term Consequences of Intracranial Haemorrhage in Children With Haemophilia","volume":"15","author":"Bladen M.","year":"2009","journal-title":"Haemophilia"},{"issue":"4","key":"e_1_2_12_33_1","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1111\/hae.12938","article-title":"The Incidence, Risk and Functional Outcomes of Intracranial Haemorrhage in Children With Inherited Bleeding Disorders at One Haemophilia Center","volume":"22","author":"Bladen M.","year":"2016","journal-title":"Haemophilia"},{"issue":"5","key":"e_1_2_12_34_1","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1007\/s11596-018-1956-4","article-title":"A Retrospective Analysis of Intracranial Hemorrhage in Children with Hemophilia A","volume":"38","author":"Hu Q.","year":"2018","journal-title":"Curr Med Sci"},{"issue":"2","key":"e_1_2_12_35_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/j.1365-2516.2011.02632.x","article-title":"Effect of Intracranial Bleeds on the Neurocognitive, Academic, Behavioural and Adaptive Functioning of Boys With Haemophilia","volume":"18","author":"Miles B. S.","year":"2012","journal-title":"Haemophilia"},{"issue":"4","key":"e_1_2_12_36_1","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.jpeds.2003.12.016","article-title":"Effect of Intracranial Bleeds on the Health and Quality of Life of Boys With Hemophilia","volume":"144","author":"Revel\u2010Vilk S.","year":"2004","journal-title":"Journal of Pediatrics"},{"issue":"1","key":"e_1_2_12_37_1","first-page":"45","article-title":"Visuoperceptual Sequelae in Children With Hemophilia and Intracranial Hemorrhage","volume":"4","author":"Morales G.","year":"2015","journal-title":"Translational Pediatrics"},{"issue":"10","key":"e_1_2_12_38_1","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1177\/0009922813495311","article-title":"Is Executive Function Intact After Pediatric Intracranial Hemorrhage? A Sample of Mexican Children With Hemophilia","volume":"52","author":"Morales G.","year":"2013","journal-title":"Clinical Pediatrics"},{"issue":"12","key":"e_1_2_12_39_1","first-page":"1629","article-title":"Intracranial Hemorrhage in Children: An Evolving Spectrum","volume":"65","author":"Lo W. D.","year":"2008","journal-title":"Archives of Neurology"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.70239","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hae.70239","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.70239","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T11:27:16Z","timestamp":1776338836000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.70239"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":38,"alternative-id":["10.1111\/hae.70239"],"URL":"https:\/\/doi.org\/10.1111\/hae.70239","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,16]]},"assertion":[{"value":"2025-11-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"hae.70239"}}