Haemophilia最新文献

{"title":"Radiological Stage of Hemophilic Arthropathy of Knee Does Not Correlate With Clinical Variables","authors":"Arman Vahabi,&nbsp;Erdem Er,&nbsp;Abdussamet Kuyucu,&nbsp;Elcil Kaya Biçer,&nbsp;Semih Aydoğdu","doi":"10.1111/hae.70088","DOIUrl":"10.1111/hae.70088","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Various functional and radiological systems have been developed to evaluate joint health and the severity of arthropathy in hemophilic patients. Clinical relevance of these radiological systems has received minimal attention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Through a retrospective chart review, 84 patients with end-stage hemophilic arthropathy of the knee were included. Pettersson and Arnold–Hilgartner scores were assessed by two observers. Correlation between radiological stage and range of motion (ROM), KSS function subscores, KSS pain subscores, total KSS, and surgical time were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Interobserver correlation was found to be very strong for Pettersson score, with a value of 0.84 (95% CI: 0.75–0.89) and moderate for the Arnold–Hilgartner with kappa value of 0.4 (95% CI: 0.17–0.62). Correlation between Pettersson score and clinical variables revealed a very weak inverse correlation with ROM (<i>r</i> = −0.12, 95% CI: −0.33 to 0.10), KSS pain (<i>r</i> = −0.09, 95% CI: −0.31 to 0.12), and KSS function (<i>r</i> = −0.16, 95% CI: −0.36 to 0.06), and weak inverse correlation with KSS (<i>r</i> = −0.24, 95% CI: −0.44 to 0.2). Regarding the correlation between Arnold–Hilgartner score, a weak inverse correlation was observed with ROM (<i>r</i> = −0.21, 95% CI: −0.41 to 0.00), and very weak inverse correlations with KSS pain (<i>r</i> = −0.06, 95% CI: −0.16 to 0.27), KSS function (<i>r</i> = −0.00, 95% CI: −0.22 to 0.21), and KSS (<i>r</i> = −0.04, 95% CI: −0.25 to 0.18).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Radiologic staging systems demonstrate weak correlation with clinically meaningful variables in patients with end-stage hemophilic arthropathy of knee, an important consideration in the management of hemophilic arthropathy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 5","pages":"1036-1042"},"PeriodicalIF":3.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.70088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Engagement to Support Shared Decision Making Within Haemophilia: Development of Materials for People With Haemophilia, Caregivers and Healthcare Professionals","authors":"Laura Meade,&nbsp;Haowei (Linda) Sun,&nbsp;Robert J. Klaassen,&nbsp;Roxana Bahar,&nbsp;Shade Olatunde,&nbsp;Michelle Santos,&nbsp;Sheri vanGunst","doi":"10.1111/hae.70062","DOIUrl":"10.1111/hae.70062","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Treatment decision making can be complex and challenging for people with haemophilia (PwH) and their caregivers. A shared decision-making (SDM) approach can ensure that decisions about treatment and care incorporate patients’ beliefs, values, and preferences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The aims were to: (1) identify potential drivers and barriers to SDM between PwH/caregivers and clinicians, (2) develop tools to facilitate SDM in clinic appointments, and (3) gain feedback on the usability and design of these tools to inform refinements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Virtual focus groups were conducted with adolescent and adult PwH, caregivers of children with haemophilia, and physicians and allied health professionals (AHPs) across Canada to inform the development of tools to support SDM in clinical appointments. The usability and acceptability of the tools were examined in one-to-one interviews. These findings were used to further refine the tools.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thematic analysis from five focus groups (<i>n</i> = 23) identified broad themes pertaining to barriers of SDM, factors influencing treatment decisions, and strategies to facilitate SDM. Insights were used to develop an Appointment Planner including pre-appointment questions and priority setting for PwH/caregivers and a Conversational Prompt Guide including considerations for clinicians. The findings of one-to-one interviews (<i>n</i> = 25) indicated good usability and acceptability and informed minor refinements to the tools.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study demonstrates the acceptability of specific tools to facilitate SDM based on qualitative research with the target populations. Initial feedback was positive. Further research is required to assess whether the tools can facilitate SDM by improving communication and strengthening relationships between PwH/caregivers and clinicians.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 5","pages":"933-948"},"PeriodicalIF":3.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measuring Physical Function Capacity in Persons With Haemophilia: A Systematic Review of Performance-Based Methods","authors":"Catherine Holdsworth,&nbsp;Melanie Bladen,&nbsp;Hannah Harbidge,&nbsp;Wendy Drechsler,&nbsp;Ryan Mahaffey,&nbsp;Sofia Perez-Alenda,&nbsp;Fionnuala Sayers,&nbsp;Karen Strike,&nbsp;Merel Timmer,&nbsp;David Stephensen","doi":"10.1111/hae.70081","DOIUrl":"10.1111/hae.70081","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Introduction&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Currently, physical health assessments in persons with haemophilia focus on bleed-related events and after-effects. The aim of the systematic review was to review and apply standardised criteria to evaluate reliability, responsiveness and construct validity of performance-based instruments evaluating physical capability in persons with haemophilia.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Medline, CINAHL, Embase, EMCARE, and Cochrane (inception-March 2024) were searched using COSMIN filters for 7 performance-based tests in haemophilia, supplemented by manual searches. Reliability, responsiveness and construct validity of the six-minute walk test (6MWT), timed up and go test (TUG), timed up and down stairs (TUDS), 30-second sit-to-stand (30-STS), single leg stance (SLS), tandem stance (TS) and single hop for distance (SH) were evaluated.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The search yielded 88 abstracts; 25 studies remained after full-text screening, covering 5 of 7 performance-based instruments: 6MWT, TUG, TUDS, SLS, and 30-STS. No performance-based test was evaluated for all properties across all ages. Only TUG in adults and older adults and 6MWT in children and adolescents has been tested for all properties. No test received a high grading. Low and very low grades were given mostly for indeterminate results, small or single studies and lack of a similar construct of comparator. The 6MWT in all age groups was the only performance-based test graded moderate, and this was for responsiveness.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;With increasing use of performance-based methods of physical function capacity, evaluating measurement properties is a priority. Until evidence is generated, we can only advocate the 6MWT to monitor responsiveness in adult persons with haemophilia affected with marked arthropathy.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;&lt;b&gt;Understanding Physical Health in People with Haemophilia&lt;/b&gt;&lt;/p&gt;\u0000 \u0000 &lt;p&gt;Currently, when we check the physical health of people with haemophilia, we mostly look at problems caused by bleeding. But we wanted to see if there are better ways to measure how well people with haemophilia can move and do daily activities.&lt;/p&gt;\u0000 \u0000 &lt;p&gt;&lt;b&gt;What We Did&lt;/b&gt;&lt;/p&gt;\u0000 \u0000 &lt;div&gt;We looked through a lot of medical studies (up to March 2024) to find information on 7 specific ph","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 5","pages":"840-864"},"PeriodicalIF":3.0,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.70081","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter in Response to the Article \"A Global Comparative Field Study to Evaluate the Factor VIII Activity of Efanesoctocog Alfa by One-Stage Clotting and Chromogenic Substrate Assays at Clinical Haemostasis Laboratories\".","authors":"Beverly Buffart, Anne Demulder, Laurence Rozen","doi":"10.1111/hae.70096","DOIUrl":"https://doi.org/10.1111/hae.70096","url":null,"abstract":"","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674548","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":"Qualification Criteria of Gene Therapy for Haemophilia—Opinion of the EAHAD Gene Therapy Working Group","authors":"Wolfgang Miesbach,&nbsp;Ana Boban,&nbsp;Pratima Chowdary,&nbsp;Michiel Coppens,&nbsp;Victor Jimenez-Yuste,&nbsp;Robert Klamroth,&nbsp;Greta Mulders,&nbsp;Miguel Crato,&nbsp;Flora Peyvandi","doi":"10.1111/hae.70090","DOIUrl":"10.1111/hae.70090","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Following the approval of the first gene therapies for haemophilia, it is essential to develop an optimal infrastructure for the administration of gene therapy. This can be ensured by identifying the criteria for the definition of treatment centres (hub centres) and follow-up centres (spoke centres), as well as establishing effective cooperation between them.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The interdisciplinary members of the EAHAD Gene Therapy Working Group answered a survey to define requirements for centres participating in gene therapy care, addressing aspects such as product administration, coagulation parameter monitoring, and long-term safety surveillance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The majority support the implementation of standardised protocols. Hub centres are expected to maintain high standards of quality and flexibility, possess pharmacist expertise, ensure regulatory compliance, and have experience in gene therapy Spoke centres should be certified haemophilia centres, access to hepatologists and providing 24-h support. Prior to gene therapy, spoke centres manage initial patient interactions, while hub centres handle complex care needs. Post-therapy, both centres can monitor factor levels and liver health. However, hub centres are responsible for managing immunosuppression and facilitating specialist consultations. Collaboration between both centres is crucial for data sharing and the assessment and resolution of adverse events, emphasising the importance of timely test results and regular liver imaging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The survey results highlight essential criteria for the safe and effective delivery of gene therapy through a structured hub-and-spoke model. These include accreditation, clinical trial experience, access to specialized healthcare professionals, and the establishment of standard operating procedures for monitoring and managing adverse events.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 5","pages":"966-972"},"PeriodicalIF":3.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.70090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced-Dose versus Standard-Dose Emicizumab for Haemophilia A: A Retrospective Cohort Study.","authors":"Huiling Yan, Dan Liu, Juan Tong, Ningling Wang, Lijun Qu, Can Gai, Jiajia Li, Jingsheng Wu, Changcheng Zheng","doi":"10.1111/hae.70092","DOIUrl":"https://doi.org/10.1111/hae.70092","url":null,"abstract":"","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659019","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":"Safety and Use of Eptacog Beta 225 µg/kg in Patients With Haemophilia A or B With Inhibitors","authors":"Manuel Carcao,&nbsp;Cédric Hermans,&nbsp;Adam Giermasz,&nbsp;Craig Kessler,&nbsp;Wolfgang Miesbach,&nbsp;Doris Quon,&nbsp;Jerzy Windyga,&nbsp;Johnny Mahlangu","doi":"10.1111/hae.70083","DOIUrl":"10.1111/hae.70083","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Eptacog beta is an activated recombinant human factor VII bypassing agent approved for treating bleeding episodes (BEs) in patients aged ≥12 years with haemophilia A or B with inhibitors. Two initial dose regimens (IDRs) of either 75 or 225 µg/kg, followed by 75 µg/kg, are approved. We examined the safety of eptacog beta 225 µg/kg across completed clinical trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This analysis included data from a Phase 1b trial of single doses of eptacog beta 25, 75 and 225 µg/kg in non-bleeding adults with haemophilia and pooled data from two Phase 3 trials of the 75 and 225 µg/kg IDRs for treating BEs in adolescents and adults (PERSEPT 1) and children (PERSEPT 2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the Phase 1b trial, 10 patients received a single eptacog beta infusion at each dose level. In the Phase 3 trials, 48 patients received the 75 µg/kg IDR (median 20.5 infusions/patient, range 1–137 infusions) and 50 patients received the 225 µg/kg IDR (median 14.5 infusions/patient, range 1–117 infusions). There was a similar incidence of treatment-emergent adverse events (TEAEs) across all doses (225, 75 and 25 µg/kg) in the Phase 1b trial (0.8 vs. 1.0 vs. 2.1 events per infusion, respectively) and with the 225 versus 75 µg/kg IDR in the Phase 3 studies (0.046 vs. 0.029 events per infusion, respectively). No treatment-related serious TEAEs, thromboembolic events, hypersensitivity reactions, deaths attributed to eptacog beta or neutralising antibodies were detected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings demonstrate favourable safety and tolerability regarding the use of the 225 µg/kg IDR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov identifier: NCT01708564, NCT02020369, NCT02448680</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 5","pages":"957-965"},"PeriodicalIF":3.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.70083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of the Individualized 4-Year Physiotherapy on the Musculoskeletal System and Quality of Life of Patients With Severe Hemophilia A With Inhibitors","authors":"Maria Podolak-Dawidziak,&nbsp;Janusz Zawilski,&nbsp;Ewa Stefańska-Windyga,&nbsp;Magdalena Górska-Kosicka,&nbsp;Anna Buczma,&nbsp;Ewa Chmielewska,&nbsp;Jolanta Oleksiuk,&nbsp;Joanna Zdziarska,&nbsp;Andrzej Mital,&nbsp;Mariola Bober,&nbsp;Justyna Kozińska,&nbsp;Michał Jamrozik,&nbsp;Monika Biernat,&nbsp;Agnieszka Brzozowska","doi":"10.1111/hae.70094","DOIUrl":"10.1111/hae.70094","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The development of factor VIII inhibitors is a significant complication of hemophilia A, increasing the risk of bleeding and resulting in high morbidity. Recurrent joint bleeds lead to severe arthropathy and a reduced quality of life compared to patients without inhibitors. Although recent therapies have improved outcomes, many patients with longstanding inhibitors already experience irreversible joint damage. Research on rehabilitation in hemophilia, particularly for patients with inhibitors, remains limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This 4-year study evaluated the impact of individualized physiotherapy on musculoskeletal health and quality of life (QoL) in severe hemophilia A patients with inhibitors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-five adults (aged 19–69) with severe hemophilia A and inhibitors received personalized home physiotherapy supervised by a specialist, alongside biannual 5-day rehabilitation camps. Prophylactic activated prothrombin complex concentrate (aPCC) was administered. Joint status was assessed biennially via Hemophilia Joint Health Score (HJHS) and MRI of target joints; QoL was measured using EQ-5D questionnaires.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No bleeding episodes occurred during prophylaxis. Thirteen patients completed follow-up. MRI scores stabilized (mean change: +1.3 points; 95% CI: 0.3–2.3), while HJHS improved significantly from 41.1 (95% CI: 32.5–49.7) to 24.9 (95% CI: 16.9–32.7). EQ-5D scores rose from 54.0 (95% CI: 48.2–59.8) to 86.7 (95% CI: 81.9–91.5), reflecting enhanced mobility, reduced pain and greater independence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Individualized rehabilitation with aPCC prophylaxis significantly improved joint function (notably pain and mobility) and QoL, despite limited MRI changes due to pre-existing arthropathy. These results advocate for long-term, tailored physiotherapy in inhibitor patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 5","pages":"1025-1035"},"PeriodicalIF":3.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659016","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":"Estimating the Factor VIII-Equivalent Activity of Emicizumab Using Global Assays of Haemostasis","authors":"Daniel Kraemmer,&nbsp;Cihan Ay,&nbsp;Judit Rejtő,&nbsp;Georg Heinze,&nbsp;Peter Quehenberger,&nbsp;Ingrid Pabinger,&nbsp;Oliver Königsbrügge","doi":"10.1111/hae.70085","DOIUrl":"10.1111/hae.70085","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Emicizumab is a bispecific monoclonal antibody mimicking factor (F) VIII activity and an effective therapy for prophylaxis in people with haemophilia A (PWHA). The FVIII-equivalent activity (FVIIIeq) of emicizumab remains unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To estimate FVIIIeq of emicizumab using global assays of haemostasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Patients/Methods</h3>\u0000 \u0000 <p>We sampled plasma from (1) PWHA of all severities and therapeutic regimens and (2) persons with severe haemophilia A on emicizumab. Thrombin generation assay (TGA) and clot formation and lysis assay (CLA) were measured by commercially available (Technothrombin, Technoclone) and turbidimetric assays, respectively. FVIII was measured by a chromogenic (CSA) and emicizumab by a modified one-stage assay (OSA). Using principal components (PC) or individual parameters as dependent and independent variables in linear regression with (1) FVIII and (2) emicizumab levels, respectively, we estimated FVIIIeq (95% CI) of emicizumab.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We collected 253 samples from 110 PWHA and 41 samples from nine individuals on emicizumab prophylaxis. TGA parameters of emicizumab-treated subjects clustered distinctly, with no correlation amongst samples with only endo-/exogenous FVIII. Consequently, FVIIIeq varied substantially between parameters: Using individual TGA parameters, endogenous thrombin potential (ETP) and thrombin peak resulted in conversion factors of 0.85 (0.60–1.24) and 0.25 (0.15–0.37) IU/dL FVIIIeq per µg/mL emicizumab, respectively. CLA parameters showed broader overlap, with an FVIIIeq estimate of 0.82 (0.44–1.38).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Distinct clustering of emicizumab and FVIII samples in TGA leads to conflicting FVIIIeq estimates between parameters, highlighting systematic limitations and questioning their clinical usefulness. A, possibly conservative, FVIIIeq conversion factor estimate as determined by the thrombin peak could range from 0.15 to 0.37.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 5","pages":"1092-1102"},"PeriodicalIF":3.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P2RY12-Related Platelet Dysfunction in an Indian Child: Unravelling the Diagnostic Enigma of Suspected Platelet Storage Pool Disorder","authors":"Vasant Kumar,&nbsp;Manu Jamwal,&nbsp;Chander Hans,&nbsp;Richa Jain,&nbsp;Jasmina Ahluwalia,&nbsp;Reena Das,&nbsp;Narender Kumar","doi":"10.1111/hae.70091","DOIUrl":"10.1111/hae.70091","url":null,"abstract":"","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 5","pages":"1145-1148"},"PeriodicalIF":3.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659017","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}