Haemophilia最新文献

{"title":"Association of TNFAIP3 Polymorphisms With Bleeding Phenotypes and FVIII Inhibitor Development in Patients With Hemophilia A: A Case-Control Study.","authors":"Fatemeh Karimi, Najmaldin Saki, Reyhane Khademi, Gholam-Abbas Kaydani, Bijan Keikhaei","doi":"10.1111/hae.70423","DOIUrl":"https://doi.org/10.1111/hae.70423","url":null,"abstract":"<p><strong>Background: </strong>Hemophilia A is an X-linked bleeding disorder caused by factor VIII (FVIII) deficiency. While F8 gene mutations are the primary cause, immune and inflammatory pathways contribute to variability in clinical phenotype and FVIII inhibitor development. TNFAIP3, encoding the immune regulatory protein A20, negatively regulates NF-κB signaling, and its polymorphisms rs2230926 and rs10499194 may influence immune responses and inhibitor susceptibility.</p><p><strong>Objectives: </strong>To investigate the association of TNFAIP3 rs2230926 and rs10499194 with clinical features and inhibitor formation in Hemophilia A patients.</p><p><strong>Methods: </strong>A case-control study included 42 patients and 70 age- and sex-matched healthy controls. Genotyping was performed using tetra-primer ARMS-PCR. Associations between genotypes, haplotypes, and clinical characteristics such as disease severity, bleeding frequency, joint involvement, Treatment interval, and inhibitor formation were analyzed using chi-square and Fisher's exact tests.</p><p><strong>Results: </strong>The rs2230926 TT genotype was predominant (97.6%). Among the 35 patients with available rs10499194 genotype data, the CC, CT, and TT genotypes were observed in 62.9%, 28.6%, and 8.6% of patients, respectively. No significant associations were observed between either polymorphism and clinical parameters or inhibitor formation. Haplotype analysis identified three major haplotypes (TC, TT, and GC), none of which was significantly associated with disease susceptibility or inhibitor risk.</p><p><strong>Conclusion: </strong>TNFAIP3 rs2230926 and rs10499194 are unlikely to be major contributors to bleeding phenotype or inhibitor development in Hemophilia A. Phenotypic variability likely results from complex interactions among genetic, immunologic, and environmental factors, warranting larger multicenter studies with comprehensive profiling.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Socio‑Economic and Education Profile of Children With Haemophilia A Receiving Prophylaxis and Their Families: Results From a Brazilian Cohort.","authors":"Patrícia Santos Resende Cardoso, Márcio Antônio Portugal Santana, Brisa Yuan Renó, Suely Meireles Rezende","doi":"10.1111/hae.70430","DOIUrl":"https://doi.org/10.1111/hae.70430","url":null,"abstract":"","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"100 Years of von Willebrand Disease (VWD): Comparison of Historical and Contemporary von Willebrand Factor (VWF) Activity Assays in the Laboratory Identification of VWD.","authors":"Emmanuel J Favaloro, Sandya Arunachalam, Mahzuza Salwa, Ronny Vong, Leonardo Pasalic","doi":"10.1111/hae.70427","DOIUrl":"https://doi.org/10.1111/hae.70427","url":null,"abstract":"<p><strong>Introduction: </strong>von Willebrand disease (VWD) is a prevalent bleeding disorder resulting from deficiencies and/or defects in von Willebrand factor (VWF). Accurately diagnosing VWD, particularly distinguishing between qualitative defects (types 2A, 2B, 2 M, and 2N) and quantitative defects (types 1 and 3), poses challenges that have significant implications for management and treatment strategies.</p><p><strong>Aim: </strong>To describe latest contemporary findings from our geographic region for laboratory-based testing.</p><p><strong>Methods: </strong>This report outlines the most recent Australasian experience, drawing on data from the Royal College of Pathologists of Australasia (RCPA) Quality Assurance Program (QAP) specifically related to VWF testing within their VWD test module. We report outcomes from the past 4 years of distributed samples (n = 16), comprising normal (n = 3), type 1 VWD (n = 4), type 2A VWD (n = 4), 2B VWD (n = 2), type 2 M VWD (n = 2) and a factor VIII deficient plasma (n = 1), supplemented with historical program experience since 1998.</p><p><strong>Results: </strong>Among testing methods, VWF:RCo and VWF:GPIbM exhibited the highest variability and error rates, with discrepancies far greater than those observed with VWF:CB and chemiluminescence-based procedures. Laboratories performing 4-test panels including a VWF:CB produced far fewer errors in VWD classification than those performing 3-test panels.</p><p><strong>Conclusion: </strong>These findings shed light on the factors contributing to elevated error rates in VWD diagnosis, indicating that certain assays and methodologies significantly outperform others.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetics of Plasma‑Derived Factor X Using Clotting and Chromogenic Assays: A WAPPS‑Hemo Model.","authors":"Dagmar M Hajducek, Pierre Chelle, Manuela Scarpellini, Andrea Edginton, Alfonso Iorio","doi":"10.1111/hae.70420","DOIUrl":"10.1111/hae.70420","url":null,"abstract":"<p><strong>Background: </strong>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-Hemo platform enables population pharmacokinetic (PopPK) individualized PK predictions based on sparse sampling.</p><p><strong>Aim: </strong>To develop and evaluate a PopPK model for Coagdex, a FX concentrate, using manufacturer-provided PK data for its implementation on the WAPPS-Hemo platform.</p><p><strong>Methods: </strong>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-free 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‑derived FX (pdFX) concentrate.</p><p><strong>Results: </strong>A two-compartment model accounting for between-occasion and between-subject variability with fat-free mass and assay-type as main covariates was selected. Evaluation showed good predictive capabilities.</p><p><strong>Conclusion: </strong>We have developed a PopPK model to support WAPPS-Hemo individualized prophylaxis in FX deficiency using sparse PK data. Prospective PK data collected through the WAPPS‑Hemo database will be used to further characterize Factor X PK and enhance patient care.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Functional Independence Score for Haemophilia (E-FISH) for Early Detection of Musculoskeletal Changes.","authors":"Sanjeev Manasseh Padankatti, S Priyadarshini, Ronald Thomvic, Paul Jebaraj, Grace Elizabeth Muppidi, Divya Jebaraj, Kavitha M Lakshmi, Tunny Sebastian, Judy Ann David, Pradeep Mathew Poonnoose, Aby Abraham, Alok Srivastava","doi":"10.1111/hae.70413","DOIUrl":"https://doi.org/10.1111/hae.70413","url":null,"abstract":"<p><strong>Background: </strong>The functional independence score in haemophilia (FISH) is a widely used performance-based assessment tool designed to evaluate musculoskeletal function in children with haemophilia (CWH). Nevertheless, FISH exhibits a ceiling effect in children who are undergoing early prophylaxis or those who present with minimal musculoskeletal impairment. This report describes the development of an enhanced FISH (e-FISH) with more challenging tasks to detect early physical function changes in CWH.</p><p><strong>Methods: </strong>Two performance-based assessments, the basketball throw test (BBT) and the 10×5-meter sprint test (ST) were included as a subtest of FISH. Age-specific normative scores were established from healthy boys. A scoring system, which ranges from 1-4, was created and compared with CWH, who showed no joint deformities after obtaining the necessary consent and assent.</p><p><strong>Results: </strong>Twenty CWH with FISH scores ranging from 31-32 and on prophylactic treatment with clotting factor concentrate were evaluated using these two tests. Only one (5%) CWH attained a higher score of 4 in both assessments. In the BBT, two (10%) achieved a score of 3, six (30%) received a score of 2, and 11 (55%) were assigned an e-FISH score of 1. In the 10×5 meter ST, eight (40%) scored 3, one (5%) scored 2, and 10 (50%) scored 1 in e-FISH. No bleeding was reported.</p><p><strong>Conclusion: </strong>We have created e-FISH as a clinimetric instrument designed for the assessment of individuals with CWH who may exhibit minimal musculoskeletal alterations and demonstrate a ceiling effect when using FISH.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidisciplinary Management of Pregnancy and Delivery in a Patient With Alloimmunized Glanzmann Thrombasthenia.","authors":"Ling-Yi Guo, Natalia Rydz, Ellen Cusano, Dawn Goodyear, Bryan Tordon, Erika Friebe, Michael B Secter, Kelsey Uminski","doi":"10.1111/hae.70421","DOIUrl":"https://doi.org/10.1111/hae.70421","url":null,"abstract":"","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perioperative Management in Persons With Haemophilia on Rebalancing Therapies: A Narrative Review.","authors":"Amanda M Henderson, Roy Khalife, Kelsey Uminski","doi":"10.1111/hae.70425","DOIUrl":"https://doi.org/10.1111/hae.70425","url":null,"abstract":"<p><strong>Introduction: </strong>Perioperative management in haemophilia often requires on-demand use of clotting factor concentrates (CFC) and/or bypassing agents. Rebalancing agents (fitusiran, concizumab, marstacimab) offer a novel approach to prophylaxis by modulating endogenous anticoagulant pathways to restore haemostatic balance. While these therapies offer advantages, such as subcutaneous delivery and factor-independent mechanisms, thromboembolic risk and optimal concurrent on-demand CFC/bypassing agent dosing perioperatively are not understood.</p><p><strong>Aim: </strong>To evaluate available evidence on the efficacy and safety of rebalancing therapies in haemophilia A or B in the perioperative setting.</p><p><strong>Methods: </strong>A narrative review of perioperative use of rebalancing therapies was conducted using targeted searches of PubMed, Scopus, and major international haematology conference abstracts through to December 2025.</p><p><strong>Results: </strong>Evidence suggests rebalancing therapies may contribute to effective perioperative haemostasis, often with reduced dosing or frequency of CFC or bypassing agents, though data is overall limited. Early studies of fitusiran and concizumab report generally favourable haemostatic outcomes in minor and selected major procedures. Perioperative bleeding events with fitusiran use are reported most often as mild to moderate and haemostasis was rated excellent/good in 90%-95% of cases. Similarly, concizumab data show bleeding events in 39/94 surgeries, the majority of which were mild to moderate. Data for marstacimab is limited but suggest feasibility with temporary interruption and CFC support.</p><p><strong>Conclusion: </strong>Limited perioperative evidence suggests that rebalancing therapies may contribute to acceptable haemostatic outcomes with reduced use of conventional haemostatic agents in selected settings. However, important clinical uncertainties remain, highlighting the need for further prospective studies.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generational Differences in Illness-Related Uncertainty Among Haemophilia Carriers: A Qualitative Study Using Mishel's Uncertainty in Illness Theory.","authors":"Tomie Fujii, Teruhisa Fujii, Teiji Uchino","doi":"10.1111/hae.70419","DOIUrl":"https://doi.org/10.1111/hae.70419","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;Haemophilia carriers (HCs) have historically been regarded as asymptomatic or only mildly affected, resulting in under-recognition of bleeding symptoms and unmet healthcare needs. Although advances in healthcare and access to information have changed the experience of haemophilia, little is known about how illness-related uncertainty differs across generations. Guided by Mishel's Uncertainty in Illness Theory, this study compared illness-related uncertainty between a younger generation of HCs and a previously studied maternal cohort.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Semi-structured interviews were conducted with nine female HCs who were adolescents and adults (17-39 years). Data were analysed thematically, and themes were deductively mapped onto Mishel's uncertainty in illness theory. The findings were conceptually compared with previously published qualitative data from 20 mothers whose daughters were haemophilia carriers. The mothers were aged 32-63 years and were interviewed in 2017.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Younger HCs had greater access to haemophilia-related information, specialist care, and patient organizations than the maternal cohort, enabling greater understanding of bleeding symptoms and genetic risk. Greater knowledge did not eliminate uncertainty but shifted its focus to disclosure to partners, reproductive decision-making, and future caregiving responsibilities. In contrast, uncertainty in the maternal cohort centred on limited awareness of carrier status, reproductive experiences, and sociocultural expectations surrounding caregiving.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Illness-related uncertainty in HCs changed rather than simply diminished across generations. Support for HCs should combine medical information, emotional support, and shared decision-making tailored to the life stage and sociocultural context.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Plain language summary: &lt;/strong&gt;Haemophilia is an inherited bleeding disorder that mainly affects boys and men, but girls and women who carry the haemophilia gene may also experience bleeding symptoms and concerns related to inheritance. Healthcare and access to information about haemophilia have improved considerably over time, but little is known about whether these changes have affected the concerns experienced by haemophilia carriers across generations. We interviewed nine female haemophilia carriers aged 17-39 years and compared their experiences with previously published findings from 20 mothers whose daughters were haemophilia carriers. The mothers were interviewed in 2017. Compared with the previously published findings, younger carriers had greater access to information, specialist healthcare, patient organizations, and family support, which helped them better understand bleeding symptoms and the possibility of passing haemophilia on to their children. However, greater knowledge did not simply remove uncertainty. Instead, younger carriers began to consider possible future","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of Glucagon-Like Peptide-1 Signaling for Hemophilic Arthropathy, Joint Inflammation, and Cartilage Degeneration: A Narrative Review.","authors":"Leonard A Valentino, Yesim Dargaud","doi":"10.1111/hae.70424","DOIUrl":"https://doi.org/10.1111/hae.70424","url":null,"abstract":"<p><strong>Introduction: </strong>Hemophilic arthropathy (HA) is a progressive, inflammatory joint disease that develops despite effective control of bleeding in people with hemophilia (PWH). Increasing evidence suggests that HA is initiated and then maintained by a complex cycle of synovial macrophage activation, angiogenesis, and cartilage catabolism-pathways shared with osteoarthritis (OA) and inflammatory arthritis. Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RA), initially developed for diabetes and obesity, have emerged as pleiotropic immunometabolic modulators with potent anti-inflammatory, chondroprotective, anti-angiogenic, and analgesic properties.</p><p><strong>Methods: </strong>A narrative review was undertaken to examine the potential role of GLP-1RA in HA.</p><p><strong>Results: </strong>Although GLP-1RA have not yet been studied directly in hemophilia, a large and growing preclinical and clinical literature in OA and inflammatory arthritis provides strong mechanistic justification for their relevance in HA.</p><p><strong>Conclusion: </strong>This review integrates experimental, translational, and epidemiologic data on GLP-1 signaling in joint biology and proposes a stage-specific framework for how GLP-1 pathways might modify HA downstream of bleeding, the initiating event.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synovial Metal Binding Proteins in Haemophilic Arthropathy: Potential Biomarkers and Therapeutic Targets.","authors":"Liyin Liu, Defu Yu, Dasheng Luo, Tao Chen","doi":"10.1111/hae.70426","DOIUrl":"https://doi.org/10.1111/hae.70426","url":null,"abstract":"<p><strong>Background: </strong>Haemophilic arthropathy (HA) is a chronic joint disease in haemophiliac patients, driven by recurrent bleeding and distinct from osteoarthritis (OA) and rheumatoid arthritis (RA) in its pathogenesis, including metal ion accumulation and inflammatory responses.</p><p><strong>Aim: </strong>To explore the role of metal ion binding proteins in HA and identify potential biomarkers and therapeutic targets.</p><p><strong>Methods: </strong>Synovial tissues from 21 patients (7 HA, 7 OA, 7 RA) were analysed using data-independent acquisition proteomics. Differentially expressed proteins were identified (fold change >2, p < 0.05) and analysed through Gene Ontology, KEGG pathways, and protein-protein interaction networks. Iron concentrations were measured via ICP-MS, and selected proteins (SOD2, CA1) were validated by immunofluorescence.</p><p><strong>Results: </strong>HA synovial tissue showed 123 and 124 differentially expressed metal binding proteins versus OA and RA, respectively, with 29 overlapping proteins. Enriched functions included iron ion binding, magnesium ion binding, calcium ion binding, zinc ion binding and copper ion binding. Key pathways involved carbon metabolism, the TCA cycle, oxidative phosphorylation, and extracellular matrix remodelling. PPI analysis highlighted hub proteins, including SOD2, NDUFS1, ACO2, IDH3A, MMP1, COL1A1, COL1A2, and LOX. ICP-MS confirmed elevated iron in HA tissues, and immunofluorescence validated protein expression trends.</p><p><strong>Conclusion: </strong>Metal binding proteins are central to HA pathogenesis, influencing oxidative stress, mitochondrial function, and extracellular matrix remodelling. These findings provide potential biomarkers and therapeutic targets for synovial-targeted regulation of metal ion homeostasis in HA.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}