Haemophilia最新文献

{"title":"Current Practice Regarding Bleeding Disorders of Unknown Cause in the Netherlands: A National Survey.","authors":"Caroline M A Mussert, Amaury L L Monard, Tirsa T van Duijl, Yvonne M C Henskens, Maartje van den Biggelaar, Roger E G Schutgens, Saskia E M Schols, Karin J Fijnvandraat, Karina Meijer, Paul L den Exter, Laurens Nieuwenhuizen, Iris van Moort, Marieke J H A Kruip, Marjon H Cnossen, Floor C J I Heubel-Moenen","doi":"10.1111/hae.70065","DOIUrl":"https://doi.org/10.1111/hae.70065","url":null,"abstract":"<p><strong>Introduction: </strong>About 40%-70% of persons with a clinically relevant bleeding tendency who are referred to haemostasis experts are classified as having a 'bleeding disorder of unknown cause' (BDUC) as no biological entity can be found after extensive laboratory testing. Currently, guidelines are under development regarding diagnostic assessment and management to minimize variation in clinical practice.</p><p><strong>Aim: </strong>Investigate current practices regarding BDUC in the Netherlands.</p><p><strong>Methods: </strong>An online survey on the best BDUC definition, associated bleeding phenotype, clinical and diagnostic approaches, treatment, registration, and follow-up was distributed amongst healthcare providers working in Dutch haemophilia treatment centres (HTCs).</p><p><strong>Results: </strong>The survey was completed by 39/54 (72%) respondents. Twenty percent did not register BDUC patients in their HTC. Healthcare professionals indicated that follow-up should depend on bleeding phenotype severity and bleeding history, and other potential causes for an increased bleeding tendency should be excluded. Moreover, the use of laboratory tests within the routine diagnostic pathway was demonstrated to be heterogeneous. Regarding treatment, tranexamic acid was most frequently prescribed for minor and major surgical interventions (79% and 86%), dental extractions (93%) and childbirth (93%). Desmopressin was prescribed for major surgical procedures by 79%.</p><p><strong>Conclusion: </strong>Our survey shows that Dutch current practice varies but is generally in line with recent ISTH SSC recommendations. Additionally, it describes other clinically relevant topics not included in the international survey, such as follow-up and exclusion of other causes for bleeding. This survey therefore adds to international efforts to unify BDUC definition, diagnostic approach, treatment and follow-up, and to attain broadly supported guidelines.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150277","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":"Factor VII Padua in Iran: A Study on 150 Patients With Factor VII Deficiency.","authors":"Seyed Mehrab Safdari, Mahmood Barati, Soudabeh Hosseini, Ebrahim Kalantar, Farhad Zaker, Akbar Dorgalaleh","doi":"10.1111/hae.70068","DOIUrl":"https://doi.org/10.1111/hae.70068","url":null,"abstract":"<p><strong>Introduction: </strong>Factor (F) VII Padua is an ultra-rare type II FVII deficiency characterized by discrepancies in FVII activity across different thromboplastin types. Due to the high prevalence of consanguineous marriages in Iran, rare bleeding disorders, including FVII deficiency, are more common. Accurate identification of FVII Padua is critical to avoid inappropriate treatments and thrombotic risks.</p><p><strong>Aim: </strong>This study aimed to determine the incidence and clinical and laboratory characteristics of FVII Padua among Iranian patients with FVII deficiency.</p><p><strong>Method: </strong>One hundred fifty Iranian patients aged 18 years or older with confirmed FVII deficiency were included. PT testing was performed using rabbit brain, human placenta and recombinant human thromboplastins. Patients with PT discrepancies consistent with FVII Padua underwent genetic analysis of F7 exon 9 for the Arg364Gln mutation.</p><p><strong>Results: </strong>Thirteen patients (8.6%) exhibited PT patterns indicative of FVII Padua. HRM analysis identified nine heterozygous and two homozygous cases for the Padua variant; subsequently, sequencing analysis confirmed the Arg364Gln variant in two patients. Sequencing also revealed four additional variants in exon 9. The confirmed Padua cases presented diverse manifestations, ranging from asymptomatic to symptomatic, including bruising, epistaxis, gastrointestinal bleeding and gum bleeding.</p><p><strong>Conclusion: </strong>FVII Padua is relatively prevalent among Iranian patients with FVII deficiency . Molecular testing is essential for accurate diagnosis, enabling appropriate management and preventing unnecessary interventions. Tailored diagnostic strategies are crucial in regions with high consanguinity rates to optimize patient care and reduce thrombotic risks.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150278","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":"Longitudinal Evaluation of Immunological Biomarkers in Previously Untreated/Minimally Treated Patients With Severe and Moderately Severe Haemophilia A During Exposure to Factor VIII: Results From the HEMFIL Study.","authors":"Márcio Antônio Portugal Santana, Daniel Gonçalves Chaves, Renan Pedra Souza, Leticia Lemos Jardim, Luciana Werneck Zuccherato, Brendon Ayala Silva Santos, Mônica Hermida Cerqueira, Claudia Santos Lorenzato, Vivian Karla Brognoli Franco, Suely Meireles Rezende","doi":"10.1111/hae.70048","DOIUrl":"https://doi.org/10.1111/hae.70048","url":null,"abstract":"<p><strong>Background: </strong>Haemophilia A (HA) is an inherited bleeding disorder due to Factor VIII (FVIII) deficiency. Treatment with FVIII can activate immune mechanisms, which may lead to inhibitor development.</p><p><strong>Objectives: </strong>This study aimed to perform a longitudinal and exploratory analysis of immunological biomarkers during replacement with FVIII concentrate and after immune tolerance induction (ITI) in patients who developed a high-responding inhibitor.</p><p><strong>Methods: </strong>Biological samples and clinical data from severe and moderately severe persons with HA (PwHA; FVIII < 0.02 IU/mL) were obtained before any or after minimal exposure (≤5 days) to FVIII (T0), at inhibitor development (INB+), at 75 exposure days (ED) without inhibitor (INB-) (T1) and at end of ITI (T2). Biomarkers were assessed at T0, T1 and T2.</p><p><strong>Results: </strong>One hundred patients were analysed, of whom 32 (86.5%) developed high-responding inhibitor and underwent ITI. We found no difference in the plasma concentration of the 15 immunological biomarkers at T0 or at T1 versus T2 in INB+ compared with INB-. However, at T1, PwHA INB+ who failed ITI had higher median concentration of interleukin (IL)-2 (3.50 vs. 0.85 pg/mL; q = 0.016), IL-10 (3.46 vs. 0.74 pg/mL; q = 0.035), tumour necrosis factor (TNF) (11.18 vs. 0.93 pg/mL; q = 0.016), interferon-gamma (INF-γ) (98.57 vs. 3.57 pg/mL; q = 0.035) and CCL5 (5245.11 vs. 3107.86 pg/mL; p = 0.037) compared with those who achieved complete response, respectively.</p><p><strong>Conclusions: </strong>Patients who failed ITI had higher concentration of IL-2, IL-10, TNF, INF-γ and CCL5 in comparison with complete responders, suggesting that these biomarkers could be potential predictors of ITI outcome.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142335","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":"Experiences and Needs Regarding Information Provision in Children With Haemophilia: A Qualitative Study on Caregivers' and Healthcare Providers' Perspectives.","authors":"Caroline M A Mussert, Nadia C W Kamminga, Evelien S van Hoorn, Tjaisha M Eekelaar, Silje R Dehli, Carolien van der Velden-van 't Hoff, Sasja Andeweg, Simone H Reitsma, Annebelle C M Nooteboom, Adinda Diekstra, Armaĝan Albayrak, Marjon H Cnossen","doi":"10.1111/hae.70063","DOIUrl":"https://doi.org/10.1111/hae.70063","url":null,"abstract":"<p><strong>Introduction: </strong>In haemophilia, ever more effective treatment options leading to minimal bleeding make information provision about the disease and its symptoms and when to alert the treatment team increasingly important. However, little is known about how current information provision is perceived and what the needs are.</p><p><strong>Aim: </strong>Gain in-depth insights into experiences and needs regarding information provision of caregivers of young children with haemophilia, and the perspectives of their healthcare providers (HCPs).</p><p><strong>Methods: </strong>A qualitative study was conducted including 15 semi-structured interviews with caregivers and seven interviews with HCPs. Purposive sampling ensured a varied sample regarding the child's age, type and severity of haemophilia, and treatment strategy. A comprehensive thematic content analysis was subsequently conducted using several phases of coding.</p><p><strong>Results: </strong>Three main themes were identified. First, caregivers and HCPs indicated that current disease knowledge and information provision regarding haemophilia varies and could be improved. Both groups underlined the importance of adequate information provision to support decision-making and alleviate anxiety. Second, the need for standardized, centralized and tailored information was expressed, preferably digital. Current information is experienced as fragmented and incomplete, leading to lack of structure and uncertainties. Lastly, information provision cannot exist without additional coaching by the multidisciplinary treatment team and peers.</p><p><strong>Conclusion: </strong>Both caregivers and HCPs experience unmet needs regarding information provision as currently performed. Empowerment can be provided by standardized, centralized information tailored to disease severity and phase of life. A digital information platform with visual support, could provide a complete, up-to-date, readily available and reliable resource.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093363","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":"Evaluation of Point-of-Care Ultrasound in Paediatric Haemophilic Arthropathy: A Prospective Comparative Study With Comprehensive Ultrasound and MRI.","authors":"Caroline Rutten, Magdy Soliman, Jyoti Panwar, Arun Mohanta, Alex Zhou, Pamela Hilliard, Tammy Rayner, Ruth Weiss, Carina Man, Rahim Moineddin, Manuel Carcao, Vanessa Bouskill, Jennifer Stimec, Kevon Dindial, Deidre Tetzlaff, Victor S Blanchette In Memoriam, Andrea S Doria","doi":"10.1111/hae.70049","DOIUrl":"https://doi.org/10.1111/hae.70049","url":null,"abstract":"<p><strong>Aim: </strong>To evaluate the diagnostic accuracy of point-of-care (POC) ultrasound (US) in detecting joint changes in haemophilic arthropathy compared to comprehensive US, physical examination and MRI.</p><p><strong>Methods: </strong>Single-centre, prospective study examining 22 ankles, eight knees and nine elbows of 28 subjects (median/range, 16/6-27 years) with inherited bleeding disorders. Same-day physical and imaging joint assessment was performed using Haemophilia Joint Health Score (HJHS) 2.1, POC-US, comprehensive US and MRI. Two readers reviewed the imaging studies using standardized scoring systems. The inter-reader agreement was assessed with weighted kappa statistics. Diagnostic test performance of POC-US and comprehensive US was benchmarked against MRI findings using sensitivity, specificity, predictive values and accuracy. Spearman correlation was used to correlate physical examination and imaging findings.</p><p><strong>Results: </strong>Moderate inter-reader agreement was observed for soft-tissue changes (kappa = 0.58), which was lower than comprehensive US (kappa = 0.76) and MRI (kappa = 0.77). Agreement for osteochondral lesions was poor (κ 0.09), trailing behind comprehensive US (kappa = 0.55) and MRI (kappa = 0.75). POC-US showed reduced accuracy across all joint parameters in the elbows and ankles compared to comprehensive US, but comparable diagnostic performance in the knees. A good correlation was noted between total POC-US scores and HJHS (r = 0.68, p < 0.0001), similar to comprehensive US (r = 0.66, p < 0.0001).</p><p><strong>Conclusion: </strong>POC-US is valuable for assessing soft-tissue changes in haemophilic arthropathy, correlates satisfactorily with physical examination, but its accuracy is inferior to comprehensive US for ankles and elbows. Both POC-US and comprehensive US should be employed cautiously for assessing osteochondral joint abnormalities.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144093421","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":"A Global Cross-Sectional Database Study of Low Dose FVIII SHL Prophylaxis in Haemophilia A.","authors":"Dagmar M Hajducek, Oceana Sinkovic, Pierre Chelle, Alfonso Iorio, Andrea Edginton","doi":"10.1111/hae.70061","DOIUrl":"https://doi.org/10.1111/hae.70061","url":null,"abstract":"<p><strong>Introduction: </strong>Haemophilia treatment is costly and only 25% of patients receive adequate care. Although not optimal, Factor VIII (FVIII) low-dose prophylaxis (LDP) may reduce annual joint bleeding rates. Understanding FVIII usage, collected through the Web-Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo) platform, and its association with Gross National Income per capita (GNI) and Universal Health Coverage index (UHCI) may provide insights in global disparities.</p><p><strong>Aims: </strong>To provide insights in FVIII use to advocate for LDP in low-income countries by providing: (i) statistical summary of FVIII usage, LDP prevalence, GNI and UHCI in WAPPS-Hemo in 2017-2023; (ii) estimation of the relationship between LDP probability (P_LDP) and GNI/UHCI for children (≤12 years) and adults; (iii) exploratory comparison of pharmacokinetics (PKs) across LDP/non-LDP.</p><p><strong>Methods: </strong>Descriptive statistics/graphical summaries for (i) and (iii), mixed-effects logistic regression for (ii).</p><p><strong>Results: </strong>Data from 6223 severe haemophilia patients (ages 0.1-92 years) showed that 18% and 32% of countries used ≤1% LDP infusions in children and adults. LDP prevalence rose annually, peaking at 7% for children and 14% for adults. GNI was found lower in LDP-prevalent countries in children. In both children and adults, P_LDP demonstrated an inverse association with GNI and UHCI. PK outcomes were similar across LDP status, except potentially for plasma-derived products in children, however limited by sample size.</p><p><strong>Conclusion: </strong>Underrepresentation of low-resource countries in WAPPS-Hemo underscores the financial challenges in haemophilia treatment. The association between GNI/UHCI and P_LDP suggests cost-driven adoption of LDP in low-resource settings, especially in children. PK outcomes average similarities may facilitate LDP-usage in WAPPS-Hemo.</p><p><strong>Trial registration: </strong>NCT02061072, NCT03533504 (ClinicalTrials.gov).</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977321","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":"Efficacy and Safety of rVIII-SingleChain in Surgical Prophylaxis.","authors":"Faraizah Abdul Karim, Johnny Mahlangu, Claudia Djambas Khayat, Jeannie Ong, Stephanie P'Ng, Johannes Oldenburg, Cindy Leissinger, Samantha Lucas, Amy Suen, Blanca Salazar, Ingrid Pabinger","doi":"10.1111/hae.70050","DOIUrl":"https://doi.org/10.1111/hae.70050","url":null,"abstract":"<p><strong>Introduction: </strong>RVIII-SingleChain is a B-domain-truncated factor VIII construct with a covalent bond between the factor VIII heavy and light chains.</p><p><strong>Aim: </strong>We report on the efficacy and safety of rVIII-SingleChain in subjects with severe haemophilia A undergoing surgery.</p><p><strong>Methods: </strong>Surgery, elective or emergent, was defined as all procedures requiring general, spinal, or regional anaesthesia. rVIII-SingleChain was administered as a bolus or continuous infusion during the perioperative period, dosed individually at the discretion of the investigator based upon the type of surgery and clinical status of the patient. The investigator rated haemostatic efficacy on a 4-point scale (excellent, good, moderate or poor/no response), where treatment success was defined as excellent or good.</p><p><strong>Results: </strong>Overall, 36 subjects underwent 48 surgeries: 41 surgeries in 30 adult/adolescent (mean age 34 [range 12-64] years) and 7 in 6 paediatric subjects (mean age 8 [5-11] years). rVIII-SingleChain was administered during 24 orthopaedic and 17 non-orthopaedic surgeries in adults/adolescents and 7 non-orthopaedic surgeries in paediatrics. Haemostatic efficacy was rated as excellent (n = 36, 88%) or good (n = 5, 12%) in adult/adolescent surgeries and as excellent (n = 7, 100%) in paediatric surgeries. In adults/adolescents, mean (standard deviation [SD]) blood loss was lower than predicted (68.6 [99.9] mL vs. 196.7 [292.8] mL); values were comparable in paediatric subjects (2.1 [2.7] mL vs. 2.9 [2.7] mL). No serious or related adverse events (AEs) were reported during the perioperative period.</p><p><strong>Conclusion: </strong>Perioperative administration of rVIII-SingleChain effectively achieves and maintains haemostatic control in adult/adolescent and paediatric subjects with haemophilia A undergoing surgery.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007357","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":"Effect of the Polymorphic Variant p.D1472H on the Platelet-Dependent VWF Activity Assays.","authors":"Omid Seidizadeh, Lismaira Pati, Luciano Baronciani, Paola Colpani, Giovanna Cozzi, Maria Teresa Pagliari, Cristina Novembrino, Andrea Cairo, Emanuela Pappalardo, Flora Peyvandi","doi":"10.1111/hae.70060","DOIUrl":"https://doi.org/10.1111/hae.70060","url":null,"abstract":"<p><strong>Background: </strong>The von Willebrand factor (VWF) p.D1472H variant has been shown to artificially lower ristocetin cofactor (VWF:RCo) levels because of impaired VWF binding to ristocetin. Understanding the variant's effect on platelet-dependent VWF activity assays is crucial for avoiding over- or misdiagnosis of von Willebrand disease.</p><p><strong>Aim: </strong>To determine whether p.D1472H affects the VWF:GPIbR latex immunoassay (LIA).</p><p><strong>Methods: </strong>We investigated 150 subjects for VWF:Ag and platelet-dependent VWF activity using four commercially available assays: VWF:GPIbR LIA, VWF:GPIbR chemiluminescence immunoassay (CLIA), VWF:RCo automated, and VWF:GPIbM LIA. p.D1472H was detected directly using Sanger sequencing or as part of other projects using next-generation sequencing (NGS).</p><p><strong>Results: </strong>A total of 106 subjects were homozygous for aspartic acid [p.D1472H (-)], 41 heterozygous, and 3 homozygous for histidine [p.D1472H (+)]. Using VWF:RCo, p.D1472H (+) subjects (n = 44) showed a significantly lower median VWF activity/VWF:Ag ratio than p.D1472H (-) subjects (p < 0.0001). No significant difference for this ratio was observed between the two groups when assessed using VWF:GPIbR LIA (p = 0.63). Similarly, no significant difference was observed in the presence or absence of the variant (p = 0.31) for the VWF:GPIbR CLIA. Using VWF:GPIbM, a significant difference (p = 0.00052) was observed between the two median ratios.</p><p><strong>Conclusions: </strong>Our results for the first time show that VWF:GPIbR LIA, despite using ristocetin, is not affected by p.D1472H; hence, it offers reliable results to differentiate VWF quantitative from qualitative deficiencies. We further confirmed that VWF:RCo is highly compromised by p.D1472H, while VWF:GPIbR CLIA is unaffected. VWF:GPIbM LIA results were significantly lower in the p.D1472H (+) subjects than those in p.D1472H (-).</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988513","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":"Real-World Unmet Needs of Patients With Haemophilia A and Haemophilia B With or Without Inhibitors: End-of-Study Results From the explorer6 Non-Interventional Study.","authors":"Allison P Wheeler, Aby Abraham, Chris Barnes, Renée Brown Frandsen, Roseline d'Oiron, Hermann Eichler, Kingsley Hampton, Francisco José López-Jaime, Chuhl Joo Lyu, Camila Martins Mazini Tavares, Keiji Nogami, Christopher Sutton, Jerzy Windyga, Bulent Zulfikar, Giancarlo Castaman","doi":"10.1111/hae.70051","DOIUrl":"https://doi.org/10.1111/hae.70051","url":null,"abstract":"<p><strong>Introduction: </strong>Haemophilia is associated with high disease and treatment burdens. Prospective evaluation of data from patients with haemophilia helps understand and define unmet needs, optimise treatment and improve healthcare outcomes.</p><p><strong>Aim: </strong>To present end-of-study data from explorer6 (NCT03741881), a prospective, non-interventional study across multiple countries in patients with haemophilia (haemophilia A or B without [HA or HB] or with inhibitors [HAwI or HBwI]).</p><p><strong>Methods: </strong>Patients ≥12 years old with severe HA, severe/moderate HB or HAwI/HBwI of any severity were treated according to the local standard of care (SoC). The number of bleeding episodes from enrolment up to a maximum of 115 weeks, physical activity based on data collected by a wrist-worn physical activity tracker, target joints and Haemophilia Joint Health Score (HJHS) measurements were assessed.</p><p><strong>Results: </strong>A total of 231 patients across 33 countries were enrolled. The mean annualised bleeding rate (ABR) (standard deviation) for treated bleeding episodes was investigated for patients receiving prophylaxis (HA: 4.7 [5.9]; HB: 2.2 [3.0]; HAwI: 10.3 [8.5]; HBwI: 12.4 [14.1]) and those receiving on-demand (OnD) treatment (HA: 21.5 [17.7]; HB: 10.5 [8.6]; HAwI: 15.2 [14.8]; HBwI: 9.3 [13.3]). Physical activity levels were lowest among patients with HBwI. Target joints were similar among haemophilia types and treatments. Overall, mean and median HJHS total scores were lower for patients receiving prophylaxis compared with OnD treatment.</p><p><strong>Conclusion: </strong>The explorer6 study assessed a large haemophilia patient population in a real-world setting across 33 countries. The results indicate that an unmet need remains among patients receiving OnD treatment and those with inhibitors.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT03741881.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016820","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":"Profiling of Anti-FVIII Antibodies in Acquired Haemophilia A: 'Insights into Domain Specificity, Isotype Variability, and Clinical Correlations'.","authors":"Ann-Cristin Berkemeier, Isabell Matuschek, Katrin Hartlieb, Thilo Albert, Natascha Marquardt, Johannes Oldenburg, Behnaz Pezeshkpoor","doi":"10.1111/hae.70056","DOIUrl":"https://doi.org/10.1111/hae.70056","url":null,"abstract":"<p><strong>Introduction: </strong>Acquired haemophilia A (AHA) is a rare autoimmune disorder caused by autoantibodies against coagulation factor VIII (FVIII), resulting in significant bleeding risks.</p><p><strong>Aim: </strong>To characterize the anti-FVIII antibody profile in AHA patients by assessing isotypes, subclasses, and correlations with key clinical parameters.</p><p><strong>Methods: </strong>Eighty AHA patients were retrospectively analysed by assessing FVIII inhibitor levels, antibody isotypes (IgG, IgA, IgM), IgG subclasses, and domain specificity using a bead-based assay. Clinical data were correlated with antibody profiles. IgG domain profiles were compared with a congenital haemophilia A (CHA) cohort.</p><p><strong>Results: </strong>The cohort had a median age of 74 years, with 60% males. Idiopathic cases accounted for 67%, and 17% had bleeding linked to medical interventions. Major bleeding sites were musculoskeletal/retroperitoneal (45%) and skin (36%). Within six months, 18% of patients died, mostly from sepsis. Anti-FVIII IgG antibodies were present in all patients, with IgG₄ (96%) and IgG₃ (60%) being the most common subclasses. IgM and IgA anti-FVIII antibodies were detected in 17.5% and 18.8% of patients, respectively, with IgM positivity associated with higher mortality (33%). IgG₄ subclass correlated significantly with inhibitor titres (r_s = 0.54; p < 0.001). Compared to CHA, AHA showed a higher prevalence of C1C2 domain-targeting antibodies (49% vs. 77%), associated with NBA levels (r_s = 0.51; p < 0.001).</p><p><strong>Conclusion: </strong>Anti-FVIII antibody profiling reveals distinct patterns in AHA, with IgG₄ linked to higher inhibitor levels. The C1C2 domain specificity of the anti-FVIII antibodies suggests a potential role of this FVIII domain in the immunopathology of AHA patients, warranting further investigation to improve prognostic tools.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969680","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}