{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T05:14:18Z","timestamp":1783314858979,"version":"3.54.6"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background<\/jats:title>\n Bleeding is the predominant clinical manifestation and one of the leading causes of death of Wiskott-Aldrich syndrome (WAS). However, significant discrepancies in reported bleeding phenotypes persist.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n This systematic review and meta-analysis aim to provide a comprehensive characterization of the bleeding phenotype and elucidate the resultant mortality burden among patients with WAS.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Observational studies reporting either the cumulative incidence of bleeding manifestations or the occurrence of fatal hemorrhagic events in patients with WAS were included. The Joanna Briggs Institute critical appraisal tool was used to assess the risk of bias. A generalized linear mixed model with a binomial-normal distribution was employed for the meta-analysis. Subgroup analyses, stratified by clinical stage at data collection, and meta-regression analyses were conducted to explore heterogeneity.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 40 studies involving 1865 patients were identified. The pooled cumulative incidences of overall and site-specific bleeding (excluding gastrointestinal bleeding), increased significantly from disease onset to diagnosis and through to the end of follow-up. At the end of follow-up, the pooled cumulative incidence of multisystem bleeding and severe bleeding was 57% (95% CI 41-72) and 19% (95% CI 12-28), respectively. Both sample size and proportion of patients with a WAS score of 5 were associated with cumulative incidence of severe bleeding at the end of follow-up (\n p<\/jats:italic>\n \u00a0=\u00a00.0042 and 0.0423, respectively). The cause-specific mortality rate from hemorrhage was 9.3% (95% CI: 6.1-13.8;\n I<\/jats:italic>\n 2<\/jats:sup>\n \u00a0=\u00a00%) in non-curatively treated patients and 1.0% (95% CI: 0.4-2.4;\n I<\/jats:italic>\n 2<\/jats:sup>\n \u00a0=\u00a00%) in curatively treated patients. Curative treatment was associated with a significantly lower risk of fatal hemorrhage compared to non-curative treatment (RR\u00a0=\u00a00.07, 95% CI 0.01-0.49). The proportional mortality ratio due to hemorrhage was 30% (95% CI 22-39) in non-curatively treated patients. Fatal hemorrhages were highly skewed toward early childhood (median age-at-death: 22 months), with intracranial hemorrhage being the predominant cause of death (76.1%).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Bleeding complications are nearly universal and progressive in patients with WAS. Given that most fatal hemorrhages occur in early childhood and curative treatment significantly mitigates this risk, prompt implementation of such therapy is imperative.<\/jats:p>\n <\/jats:sec>\n \n Systematic review registration<\/jats:title>\n \n https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:ext-link>\n , identifier CRD420261277891.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1854833","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T04:20:25Z","timestamp":1783311625000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The spectrum of bleeding in Wiskott-Aldrich syndrome: a systematic review and meta-analysis of incidence and mortality"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhicheng","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Rheumatology & Immunology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyun","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology & Immunology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Rheumatology & Immunology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfei","family":"An","sequence":"additional","affiliation":[{"name":"Department of Rheumatology & Immunology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity","place":["Chongqing, China"]},{"name":"Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, College of Pharmacy, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Rheumatology & Immunology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongxin","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Rheumatology & Immunology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity","place":["Chongqing, 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