Haemophilia最新文献

{"title":"Acquired Haemophilia A and COVID-19 mRNA Vaccine Tozinameran: Analysis of Cases Registered in the French PharmacoVigilance Database.","authors":"Marine Laeng, Aude Lambert, Sophie Gautier, Marie Briet, Marie-Léa Piel-Julian, Joëlle Micallef","doi":"10.1111/hae.70303","DOIUrl":"https://doi.org/10.1111/hae.70303","url":null,"abstract":"<p><strong>Background: </strong>Acquired haemophilia A (AHA) is a rare autoimmune bleeding disorder commonly associated with autoimmune disorders, malignancies, infections, pregnancy, and certain medications. During the COVID-19 vaccination campaign, several case reports have documented instances of AHA occurring subsequent to SARS-CoV-2 vaccination. In France, enhanced real-time surveillance for adverse drug reactions (ADRs) associated with tozinameran/BNT162b2 (Pfizer-BioNTech, Comirnaty) identified a potential signal for AHA in April 2021.</p><p><strong>Objectives: </strong>To investigate the potential signal for AHA following tozinameran vaccination by analyzing spontaneous reports recorded in the French Pharmacovigilance Database (FPVD).</p><p><strong>Patients/methods: </strong>We conducted pharmacological and medical analyses of AHA cases following tozinameran vaccination registered in the FPVD. A total of 27 cases were included.</p><p><strong>Results: </strong>AHA typically occurred after the second dose with a median onset of 23 days. The most frequent symptom was spontaneous haematoma. Haemorrhagic syndrome was severe in 19 cases due to associated anaemia. Seventeen patients received anti-haemorrhagic agents, and 23 patients were treated with corticosteroids alone or combined with immunosuppressive agents. The mortality rate was 15%. No alternative etiology for AHA was identified in most cases, despite thorough investigations. Two patients experienced worsening of symptoms after re-exposure to tozinameran.</p><p><strong>Conclusions: </strong>This study supports a potential AHA signal with tozinameran, emphasizing the need for awareness among healthcare professionals.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836466","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":"Gait Pattern at Different Speeds in Persons With Haemophilia.","authors":"Marius Brühl, Pia Möllers, Jamil Hmida, Fabian Tomschi, Georg Goldmann, Frank A Schildberg, Johannes Oldenburg, Andreas C Strauss, Thomas Hilberg","doi":"10.1111/hae.70305","DOIUrl":"https://doi.org/10.1111/hae.70305","url":null,"abstract":"<p><strong>Introduction: </strong>Persons with haemophilia (PwH) have a risk of bleeding in joints, especially in elbow, knee and ankle. In the long term, this leads to haemophilic arthropathy (HA), which results in joint deformities.</p><p><strong>Aim: </strong>This study aims to examine how walking speed and HA affect (1) foot pressure distribution, (2) average vertical peak pressure, and (3) knee and ankle joint angles during walking.</p><p><strong>Methods: </strong>Using a motion analysis system (DIERS 4DmotionLab), 30 PwH and 31 healthy controls (CG) were examined at speeds of 3, 4, and 5 km/h. Groups were additionally divided according to the severity of HA, in the subgroups PwH(major) and PwH(minor).</p><p><strong>Results: </strong>Regarding different gait speeds, no differences were found between PwH and CG in peak pressure distribution. However, pedobarography showed a significant reduction in average vertical peak pressure in the second half of the stance phase in PwH(major) compared to CG (p < 0.007). Joint angle measurements showed reduced plantar flexion (p = 0.041), dorsiflexion (p = 0.011), and descriptive, non-significant knee flexion in PwH(major) at different speeds. Knee extension did not differ between groups.</p><p><strong>Conclusion: </strong>The study confirms that PwH, especially those with advanced HA, show impaired gait pattern. While different walking speeds had no impact on peak pressure values compared to CG, force transmission was reduced in PwH in the second half of the stance phase. This, in conjunction with reduced mobility in the ankle joints, indicates impaired power transmission in the propulsion phase which is well compensated.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836689","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":"Successful Treatment of Heavy Menstrual Bleeding in a Woman With Mild Haemophilia A Using Efanesoctocog Alfa.","authors":"Michael Iarossi, Abdelwahab Boulekbache, Pierre Fontana, Alessandro Casini","doi":"10.1111/hae.70289","DOIUrl":"https://doi.org/10.1111/hae.70289","url":null,"abstract":"","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836740","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":"Beyond Standard Half-Life: Real-world Pharmacokinetics of Efanesoctocog Alfa in a Single Centre.","authors":"Laurent Sattler, Agathe Herb, Léa Pierre, Jordan Wimmer, Manon Dolt, Olivier Feugeas, Dominique Desprez","doi":"10.1111/hae.70306","DOIUrl":"https://doi.org/10.1111/hae.70306","url":null,"abstract":"<p><strong>Introduction: </strong>Efanesoctocog alfa (EFA) is an ultra-extended half-life factor VIII (FVIII) developed to address limitations of conventional prophylaxis in haemophilia A. Although the XTEND trials reported low interindividual pharmacokinetic (PK) variability, real-world data remain important to better characterize PK profiles across patient subgroups.</p><p><strong>Aim: </strong>To report real-world PK data for EFA.</p><p><strong>Methods: </strong>In this single-centre study, adults and children (>6 years) with severe haemophilia A at Strasbourg University Hospital switched from a prior FVIII product to EFA. A simplified PK assessment was performed once or twice per patient after a 50 IU/kg infusion. FVIII activity was measured pre-infusion and at 3, 24, 96 h, and 7 days post-infusion. Patients were reassessed at steady state after ≥6 weeks.</p><p><strong>Results: </strong>In adults, mean (range) half-life was 52 h (35-62). Mean incremental recovery at 3 h was 2.98 IU/dL per IU/kg (1.85-3.82). Mean FVIII trough levels were 17 IU/dL (5-27) at switch and 19 IU/dL (10-27) at steady state. Significant interindividual variability was observed. Half-life correlated positively with VWF:Ag levels (r = 0.63; p < 0.05) and body weight (r = 0.62; p < 0.05). In children, mean half-life was 53 h (48-59), mean recovery 2.05 IU/dL per IU/kg (1.86-2.26), and trough levels 13-14 IU/dL.</p><p><strong>Conclusions: </strong>PK profiles matched or exceeded those reported in the XTEND studies, with a slightly longer half-life and higher trough FVIII levels. Notable interindividual variability highlights the value of PK assessments, even for ultra-extended half-life FVIII, to optimize individualized patient management.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836487","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 Static and Dynamic Balance, and the Associations of Joint Health, Physical Activity and Kinesiophobia on Dynamic Balance in Adults With Haemophilia.","authors":"Ayşe Merve TaT, Necati Muhammed TaT, Pervin Yeşiloğlu, Ali Doğan","doi":"10.1111/hae.70304","DOIUrl":"https://doi.org/10.1111/hae.70304","url":null,"abstract":"<p><strong>Introduction: </strong>Postural balance may be affected in adults with haemophilia (AwH). Studies report decreased dynamic balance (DB), but results of static balance (SB) are contradictory in AwH. The causes of DB impairment and its associated parameters are underexplored.</p><p><strong>Aim: </strong>To examine SB and DB, and relationship of DB with joint health (JH), physical activity (PA) and kinesiophobia and, the factors contributing of DB impairment.</p><p><strong>Methods: </strong>This cross-sectional study included 43 AwH and 40 healthy men. The study groups were haemophilia group (HG) and control group (CG). SB and DB were assessed with the Posturographic Platform, and PA with International Physical Activity Questionnaire (IPAQ) for all groups. JH and kinesiophobia were evaluated with Haemophilia Joint Health Score (HJHS) and Tampa Scale for Kinesiophobia (TSK) for HG.</p><p><strong>Results: </strong>There was no significant difference in age, BMI and IPAQ between the groups (p = 0.19, p = 0.052, p = 0.96, respectively). DB was significantly lower in HG than in CG (p = 0.03). Forward-back velocity, perimeter, and mediolateral trunk sway from SB parameters in open eyes (p <0.001, p = 0.048, and p = 0.008, respectively) and eyes closed (p = 0.011, p = 0.082 and p = 0.027, respectively), and total trunk sway in open eyes (p = 0.034) were significantly higher in HG than CG. DB was correlated with JH (r = -0.551, p < 0.001) and PA (r = 0.357, p = 0.019). Univariable regression analysis showed that only DB and JH were significant (p < 0.001, R² = 0.50).</p><p><strong>Conclusion: </strong>This study revealed that SB and DB were negatively affected in AwH. DB was associated with JH and PA, with poor JH largely explaining the reduction in DB.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836649","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":"Rate of Prophylaxis for Heavy Menstrual Bleeding Management in Women With von Willebrand Disease.","authors":"Michelle Millions, Jaclyn Shelton, Haowei Linda Sun","doi":"10.1111/hae.70286","DOIUrl":"https://doi.org/10.1111/hae.70286","url":null,"abstract":"","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836675","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 Use of Emicizumab in Patients With Acquired Haemophilia A: An Interim Safety Analysis of a Large-Scale Post‑Marketing Surveillance Study.","authors":"Midori Shima, Katsuyuki Fukutake, Yoshiyuki Ogawa, Yuta Kamei, Chiaki Sugita, Akinori Yuri, Ryota Kobayashi, Akiko Ioka, Tadashi Matsushita","doi":"10.1111/hae.70301","DOIUrl":"https://doi.org/10.1111/hae.70301","url":null,"abstract":"<p><strong>Introduction: </strong>Acquired haemophilia A (AHA) is a rare autoimmune disorder where the development of autoantibodies to factor (F)VIII neutralise its function, leading to bleeding. Emicizumab has been approved for treating AHA in Japan.</p><p><strong>Aim: </strong>This post-marketing study was performed to primarily examine the use and safety of emicizumab, and indirectly assess effectiveness, for AHA patients in clinical practice in Japan.</p><p><strong>Methods: </strong>This post-marketing surveillance study is being conducted in patients with AHA who receive emicizumab and immunosuppressive therapy (IST). For each patient, the observation period is from the first day of emicizumab to 4 weeks after the last administration, up to 24 months. The primary endpoint is adverse events (AEs).</p><p><strong>Results: </strong>The first 51 patients who completed the survey were included in this interim analysis; 34 (66.7%) were male, and the median (range) age was 76.0 (33-91) years. Twenty-five (49.0%) patients experienced 63 AEs (45 serious). One thromboembolism occurred: cerebral infarction, unrelated to emicizumab. Nine (17.6%) patients died, due to infection (n = 4), haemorrhage (n = 3) and 'other' (n = 2), with no causal relationship with emicizumab in any case. Excluding the Week 1 emicizumab loading dose period, 8 (15.6%) patients received recombinant FVIIa while on emicizumab. All patients received IST from Day 1 (median initial prednisolone dose: 0.93 mg/kg). Median FVIII activity (one-stage assay) reached ∼60% in the patients who completed emicizumab treatment, and continued increasing after completion.</p><p><strong>Conclusions: </strong>This post-marketing study confirmed that emicizumab is well tolerated in patients with AHA, with no unexpected safety concerns. The benefit-risk profile of emicizumab remains favourable.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769773","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":"Considerations for the Use of AAV-based Gene Therapy in HIV-Positive Individuals With Haemophilia.","authors":"Jürgen K Rockstroh, Julia C Stingl, Marco Stadler, Anja Reichert, Heiner Wedemeyer, Johannes Oldenburg","doi":"10.1111/hae.70299","DOIUrl":"https://doi.org/10.1111/hae.70299","url":null,"abstract":"<p><strong>Introduction: </strong>There is a high prevalence of human immunodeficiency virus (HIV) infection among the haemophilia community due to treatment in the 1970s and 1980s with contaminated clotting factor. Lifelong treatment regimens for haemophilia and HIV are burdensome alone and pose a particular challenge for individuals living with both conditions. Adeno-associated virus (AAV)-based gene therapy restores endogenous factor expression and offers an alternative to routine prophylaxis for haemophilia that individuals living with haemophilia and HIV infection may find uniquely appealing to alleviate the treatment burden for at least one of their chronic conditions.</p><p><strong>Aim: </strong>The aim of this article is to provide guidance on clinical practice to health care professionals considering gene therapy as a treatment option for individuals with haemophilia and HIV.</p><p><strong>Methods: </strong>We compile available safety and efficacy evidence from participants living with HIV who participated in gene therapy trials for haemophilia. Then, based on this evidence, we provide several HIV-specific considerations for individuals with haemophilia and HIV comorbidity.</p><p><strong>Conclusion: </strong>As part of a shared decision-making approach, it is important to not only evaluate if gene therapy is appropriate but also to offer recommendations on what to expect when navigating the treatment journey. The available evidence to date indicates modern antiretroviral therapy (ART) regimens may not cause complications when combined with AAV-based gene therapies. Accordingly, HIV infection should not be considered a general contraindication for gene therapy to restore factor expression in haemophilia. However, a careful consideration of the individual's life context, especially hepatotoxic drug effects or interactions, is warranted.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769851","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 X and Combined Factor VIIa/Factor X Augment Coagulation Potential in a Plasma Model of Tissue Factor Pathway Inhibitor-Reduced Haemophilia State.","authors":"Shigeharu Oh, Yuto Nakajima, Eisuke Takami, Hirotoshi Nakano, Keiji Nogami","doi":"10.1111/hae.70297","DOIUrl":"https://doi.org/10.1111/hae.70297","url":null,"abstract":"","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769820","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 Effectiveness and Safety of Concizumab Prophylaxis in Hemophilia: Results From a National French Cohort.","authors":"Caroline Galeotti, Antoine Rauch, Helene Gatti, Stephanie Desage, Alexandre Butelet, Christine Biron-Andreani, Sophie Susen, Roseline d'Oiron, Guillaume Chanteau, Valerie Proulle, Yesim Dargaud","doi":"10.1111/hae.70290","DOIUrl":"10.1111/hae.70290","url":null,"abstract":"<p><strong>Background: </strong>Inhibition of tissue factor pathway inhibitor represents an advanced rebalancing strategy for hemophilia, applicable across hemophilia A and B irrespective of inhibitor status. Although concizumab has demonstrated efficacy in clinical trials, real-world data remain very limited.</p><p><strong>Objectives: </strong>To evaluate the real-world effectiveness and safety of concizumab prophylaxis in an unselected national cohort of patients treated in routine clinical practice in France.</p><p><strong>Methods: </strong>This cross-sectional observational study included all patients receiving concizumab through compassionate-use or Early Access Programs across six French hemophilia centers. Retrospective data were collected from treatment initiation to a predefined cutoff (1, December 2025). Outcomes included bleeding rates, target joint status, surgical management, laboratory monitoring practices, adherence, and adverse events.</p><p><strong>Results: </strong>Eleven patients were included, ten with hemophilia B with inhibitors and one with hemophilia B without inhibitors. Mean exposure to concizumab was 22.8 months. Compared with the pre-treatment period, concizumab prophylaxis was associated with a marked reduction in bleeding, including complete absence of bleeding in four patients and resolution of target joints in nine of ten patients. Nine surgical procedures, including two major surgeries, were performed under concizumab prophylaxis with concomitant rFVIIa without thrombotic complications. No thrombotic events or injection-site pain were reported. None of the patients discontinued concizumab prophylaxis.</p><p><strong>Conclusions: </strong>In this nationwide real-world cohort, concizumab prophylaxis was effective, well tolerated, and manageable in routine practice, including during surgical procedures. These data support its use as a valuable prophylactic option in carefully selected patients with hemophilia B and inhibitors, while underscoring the importance of individualized monitoring and thrombotic risk assessment.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769841","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}