Haemophilia最新文献

{"title":"Real-world effectiveness of eptacog beta in patients with haemophilia and inhibitors: A multi-institutional case series","authors":"Kimberley Youkhana,&nbsp;Glaivy Batsuli,&nbsp;Suchitra Acharya,&nbsp;Osman Khan,&nbsp;Duc Q. Tran,&nbsp;Andrea Dvorak,&nbsp;Michael Recht,&nbsp;Guy Young,&nbsp;Robert Sidonio Jr.,&nbsp;Yasmina Abajas","doi":"10.1111/hae.15094","DOIUrl":"10.1111/hae.15094","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The management of bleeding events (BEs) in haemophilia A (HA) and B (HB) patients with inhibitors necessitates the use of bypassing agents. The recombinant factor VIIa bypassing agent eptacog beta has demonstrated efficacy at treating BEs and managing perioperative bleeding in adults in phase three clinical studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To provide real-world descriptions of eptacog beta use for BE treatment in patients on emicizumab or eptacog beta prophylaxis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is a retrospective case series of 14 patients who received eptacog beta at seven haemophilia treatment centres, with HA (<i>n</i> = 11) or HB (<i>n</i> = 3) and inhibitors or anaphylaxis to factor replacement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-four spontaneous and traumatic BEs are described (muscle hematomas, joint hemarthroses, port site, and epistaxis) involving 11 subjects. Eptacog beta was effective for acute bleed treatment as both first-line therapy and for treatment of BEs refractory to eptacog alfa in 23/24 events. When eptacog beta was used for prophylaxis, 2/3 patients reported a decreased frequency of breakthrough BEs compared with prophylactic eptacog alfa and one patient experienced a similar frequency of breakthrough BEs compared with prophylactic activated prothrombin complex concentrate. Eptacog beta provided effective bleed control for three subjects who underwent minor surgical procedures. Treatment with eptacog beta was estimated to be 46%–72% more cost-effective than eptacog alfa. No safety concerns or adverse events were reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this case series, eptacog beta was safe, effective, and economical as first-line therapy, treatment of refractory BEs, management of perioperative bleeding, or prophylaxis in haemophilia patients with inhibitors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 6","pages":"1321-1331"},"PeriodicalIF":3.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.15094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284428","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":"We need better health-related quality-of-life data for children with haemophilia in lower-income countries","authors":"Matthew Speckert,&nbsp;Vid Bijelić,&nbsp;Ewurabena Simpson,&nbsp;Robert J. Klaassen","doi":"10.1111/hae.15095","DOIUrl":"10.1111/hae.15095","url":null,"abstract":"","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 6","pages":"1429-1431"},"PeriodicalIF":3.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284429","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":"Pathogenesis of osteoarthritis, rheumatoid arthritis, and hemophilic arthropathy: The role of angiogenesis","authors":"Laura Caliogna,&nbsp;Micaela Berni,&nbsp;Camilla Torriani,&nbsp;Maria Elisa Mancuso,&nbsp;Matteo Nicola Dario Di Minno,&nbsp;Alice Maria Brancato,&nbsp;Eugenio Jannelli,&nbsp;Mario Mosconi,&nbsp;Gianluigi Pasta","doi":"10.1111/hae.15097","DOIUrl":"10.1111/hae.15097","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The term ‘chronic inflammatory arthritis’ (IA) can be used to define a group of heterogeneous diseases in which inflammation of the synovium is the common feature while having different pathogenesis and clinical outcomes. This condition can be found in osteoarthritis (OA), rheumatoid arthritis (RA), and hemophilic arthropathy (HA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The objective is to try to highlight similarities and differences in the three pathological conditions and understand both molecular and physiological mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We have carried out a systematic review of the available literature following the guidelines Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>By comparing the data in the literature on OA, RA, and HA we have shown that the three pathologies differ in initial etiology but they motivate the same molecular pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this review we highlighted the similarities and differences between these diseases, creating ideas for future studies both in vivo and in vitro to develop new therapeutic agents and suggest possible biomarkers to follow the evolution and severity of the disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 6","pages":"1256-1264"},"PeriodicalIF":3.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.15097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142250687","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":"Development of the coreHEM mental health patient-reported outcome measure – A novel mental health outlook measure for people with haemophilia","authors":"Elizabeth Clearfield,&nbsp;Hsing-Yuan Chang,&nbsp;Ellen M. Janssen,&nbsp;Tabassum Majid,&nbsp;Donna A. Messner,&nbsp;Donna Coffin,&nbsp;Mohit Jain,&nbsp;Paul E. Monahan,&nbsp;Leonard A. Valentino,&nbsp;Michelle Witkop,&nbsp;Mark W. Skinner","doi":"10.1111/hae.15085","DOIUrl":"10.1111/hae.15085","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Currently, no quality-of-life instrument exists that captures the full experience of the mental health outlook (MHO), a coreHEM core outcome, in people with haemophilia, including the potential transformational experience of receiving gene therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To describe the methods used to develop a content validated patient-reported outcome measure (PROM) that measures MHO for people with haemophilia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A conceptual framework, developed from a literature/evidence review, was used to create an interview guide and draft a questionnaire. Males aged 15 or older with severe/moderate haemophilia were eligible to participate in concept elicitation or cognitive debriefing interviews. The conceptual framework was refined based on a thematic analysis of concept elicitation interviews and PROM items were developed from the conceptual framework. Cognitive debriefing sessions that prioritised relevance and understanding of the PROM were held in two rounds; items were updated iteratively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A conceptual framework with five domains (stigma, anxiety, depression, life interference and identity) was constructed from over 300 identified MHO concepts. Fifty-three participants took part in interviews. After 32 concept elicitation interviews, the framework was updated by including eight new sub-concepts and eliminating two. Updates to the questionnaire included items added or removed and improved wording. The final coreHEM MHO PROM has 26 questions in two sections (general mental health associated with haemophilia, and a gene therapy section).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The instrument is content-validated and can be used as an exploratory outcome. MHO scores can be measured and compared to give more insight into patient quality of life.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 6","pages":"1309-1320"},"PeriodicalIF":3.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.15085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139963","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":"Determination of body composition by dual x-ray absorptiometry in persons with haemophilia","authors":"Pia Ransmann,&nbsp;Marius Brühl,&nbsp;Jamil Hmida,&nbsp;Georg Goldmann,&nbsp;Johannes Oldenburg,&nbsp;Anna Christina Strauss,&nbsp;Thorsten Hagedorn,&nbsp;Frank Alexander Schildberg,&nbsp;Thomas Hilberg,&nbsp;Andreas Christian Strauss","doi":"10.1111/hae.15091","DOIUrl":"10.1111/hae.15091","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>There is limited research on body composition in persons with haemophilia (PwH). The literature describes an increased body fat distribution and decreased lean mass in PwH compared to healthy controls using bioimpedance analysis. Using dual x-ray absorptiometry (DXA), which is known to be the most accurate method, this investigation aims to postulate reference data for body composition parameters within haemophilia severity phenotypes and age groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Persons underwent whole body DXA screening using Horizon. Body fat percentage, estimated visceral adipose tissue (VAT), appendicular fat and lean mass, and lean and fat mass in relation to body height were assessed. Haemophilia severity and five age groups were distinguished.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Two hundred and one persons with mild (<i>n</i> = 44), moderate (<i>n</i> = 41), or severe (<i>n</i> = 116) haemophilia A/B (median age 40 [28–55; 1.IQ–3.IQ] years) were analysed. The median body fat percentage was 28.7% [25.5%–33.9%] and median estimated VAT was 657 g [403–954 g] with no significant difference between severity phenotypes (<i>p</i> = .474; <i>p</i> = .781). Persons with severe haemophilia had less lean mass compared to moderate and mild haemophilia (<i>p</i> = .013; <i>p</i> = .034). Total and appendicular fat is increased in older PwH (aged ≥40 years) compared to younger PwH (aged ≤29 years; <i>p</i> &lt; .05). Lean mass did not differ between age groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provides valuable reference data for body composition parameters in PwH. Persons with severe haemophilia show significantly less lean mass compared to persons with moderate or mild haemophilia. Body fat percentage and VAT did not differ between severity phenotypes, but increased with age.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 6","pages":"1332-1340"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.15091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142106730","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":"Differences and similarities in patient-reported outcomes among men and women with haemophilia","authors":"Christine L. Kempton,&nbsp;Sara A. Guasch,&nbsp;Tyler W. Buckner,&nbsp;Shanna Mattis,&nbsp;Stacey A. Fedewa","doi":"10.1111/hae.15090","DOIUrl":"10.1111/hae.15090","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Both men and women can be diagnosed with haemophilia and the experience with haemophilia may be different between men and women.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study aimed to compare patient-reported outcomes in men versus women with haemophilia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study is a post-hoc analysis of data collected as part of the Haemophilia-related Distress Questionnaire validation study. Adults aged ≥18 years with haemophilia A or B were recruited from one of two haemophilia treatment centres between July 2017 and December 2019. Outcomes included quality of life, measures of mental and physical health, and overall health. Unadjusted and multivariable linear regression models were used to examine potential mediators of sex-based differences in outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 139 study participants included (21 women, 118 men), the mean age was 36.9 years and most (89.2%) had haemophilia A. Approximately 85.7% and 26.3% of women and men had mild haemophilia, respectively.  PHQ-9 depression and PROMIS-29 Profile anxiety and fatigue scores were significantly higher in women than men in unadjusted and adjusted analyses. There were no statistically significant differences in other outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Women with haemophilia are more likely to experience depression, anxiety, and fatigue than men with haemophilia. This study highlights the need for mental health services to be integrated into the care of women with haemophilia. Future research is needed to understand whether women with haemophilia are more or less likely to experience depression, anxiety, and fatigue than women without haemophilia as well as determine the impact of reduced mental health on clinical outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 6","pages":"1383-1392"},"PeriodicalIF":3.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.15090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072601","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":"Comprehensive laboratory assessment of lonoctocog alfa versus octocog alfa in severe haemophilia A","authors":"Jens Müller,&nbsp;Thilo Albert,&nbsp;Claudia Klein,&nbsp;Silvia Horneff,&nbsp;Heiko Rühl,&nbsp;Bernd Pötzsch,&nbsp;Georg Goldmann,&nbsp;Natascha Marquardt,&nbsp;Johannes Oldenburg","doi":"10.1111/hae.15089","DOIUrl":"10.1111/hae.15089","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Lonoctocog alfa is a single-chain factor VIII (FVIII) molecule with high binding affinity to von-Willebrand-factor. While it is well known that its plasma activity is underestimated by one-stage clotting assays (OSCA), there is a lack of knowledge on the post-infusion performance of lonoctocog alfa in global coagulation assays or its potential impact on the haemostatic balance in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To characterize lonoctocog alfa versus octocog alfa in pre- and post-infusion samples obtained from patients undergoing repeated investigation of incremental recovery (IR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eighteen patients with severe haemophilia A (lonoctocog alfa: 10, octocog alfa: 8) were included. A panel of factor-specific and global coagulation assays was applied, comprising a FVIII OSCA, two FVIII chromogenic substrate assays (CSA), rotational thrombelastography and thrombin generation (TG). Potential activation of coagulation was assessed by measuring plasma thrombin markers and levels of activated protein C.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Comparable IRs were found for lonoctocog alfa and octocog alfa (2.36 [IU/dL]/[IU/kg] vs. 2.55 [IU/dL]/[IU/kg], respectively). Lonoctocog alfa activities were found to be underestimated by the FVIII OSCA while also the two FVIII CSAs showed statistically significant assay discrepancies on lonoctocog alfa. Effects of both FVIII products on rotational thrombelastography were less distinct than those on TG parameters. No elevated pre- or significantly shifting post-infusion plasma levels of coagulation biomarkers were detected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Lonoctocog alfa and octocog alfa showed comparable recovery and safety in vivo as well as similar impacts on TG in vitro. Observed assay discrepancies on lonoctocog alfa demonstrated variability of results also between different FVIII CSAs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 5","pages":"1203-1209"},"PeriodicalIF":3.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.15089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008676","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":"Driving improvement of diagnosis and awareness of heavy menstrual bleeding in women among physicians","authors":"Rezan Adbul Kadir,&nbsp;Ahmad Tarawah,&nbsp;Naveen Shridhar,&nbsp;Roshni Kulkarni","doi":"10.1111/hae.15088","DOIUrl":"10.1111/hae.15088","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>A number of barriers in care exist for women/girls with bleeding disorders. Little progress has been made to overcome them, particularly regarding levels of awareness of healthcare professionals (HCPs) and women/girls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To evaluate awareness and perception of heavy menstrual bleeding (HMB) and bleeding disorders among HCPs and women/girls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A three-part qualitative study was conducted, including HCPs and women/girls from over seven countries. Part 1 included eleven 60-min interviews with experts discussing HMB diagnostic barriers, which were further assessed in surveys among 6099 women/girls, 353 general practitioners (GPs), and 426 obstetricians and gynaecologists (OB/GYNs) during Part 2. Part 3 included three 1.5–2-h workshops with 20 clinicians and patient representatives covering HMB knowledge, criteria defining HMB and HCP resourcing for diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Many HCPs do not conduct certain investigations for women/girls presenting with HMB, and 22% of GPs lack confidence in the management of HMB. Only 8% of GPs use screening tools to evaluate menstrual blood loss, and 13% of GPs and 15% of OB/GYNs assess underlying bleeding disorders. Seventy-six percent of menstruating women/girls believed they could recognise HMB symptoms ‘well’. However, 23% of these women/girls would not seek medical advice for abnormal/prolonged menstruation disrupting their lives. Disruptions were reported in 34% of women/girls from the general population and 61% of women with at-risk symptoms of HMB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Many women/girls and HCPs have limited awareness of important HMB indicators. There is a need for standardized clinical criteria to promote efficient diagnoses and management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 5","pages":"1185-1192"},"PeriodicalIF":3.0,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.15088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008677","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":"Transitioning patients with severe haemophilia A from emicizumab prophylaxis to valoctocogene roxaparvovec gene therapy: Real-world clinical experience","authors":"Robert Klamroth,&nbsp;Saskia Gottstein","doi":"10.1111/hae.15086","DOIUrl":"10.1111/hae.15086","url":null,"abstract":"&lt;p&gt;Dear Editor&lt;/p&gt;&lt;p&gt;Valoctocogene roxaparvovec is a gene therapy that has been approved for the treatment of adults with severe haemophilia A since 2022 in Europe and 2023 in the USA.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; It uses an adeno-associated virus serotype 5 to deliver a functional copy of the B-domain-deleted factor VIII (FVIII)-encoding gene, &lt;i&gt;F8&lt;/i&gt;, to hepatocytes, via a single infusion, to allow long-term expression of endogenous FVIII and prevention of bleeding in adults with severe haemophilia A.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Emicizumab, a humanised, recombinant, bispecific monoclonal antibody, has been approved in the USA and Europe since 2018 as routine prophylaxis for patients with severe haemophilia A, regardless of FVIII inhibitor status.&lt;span&gt;&lt;sup&gt;4-6&lt;/sup&gt;&lt;/span&gt; Emicizumab is administered subcutaneously at a dose of 3 mg/kg once weekly for the first 4 weeks, followed by a maintenance dose of 1.5 mg/kg once every week, 3 mg/kg once every 2 weeks or 6 mg/kg once every 4 weeks.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; It acts by mimicking the function of activated FVIII and has a half-life of approximately 28−34 days.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Whilst the availability of gene therapy for severe haemophilia A represents a significant therapeutic milestone, new therapies may pose challenges to physicians on how to practically implement them within a patient's current treatment regimen. One such topic, addressed in the July 2024 issue of &lt;i&gt;Haemophilia&lt;/i&gt;, is how to transition patients from one therapy to another.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; Agarwal et al. used pharmacokinetic simulations to determine best practice for maintaining haemostatic control whilst transitioning patients from emicizumab prophylaxis to valoctocogene roxaparvovec gene therapy. Bleeding risk was estimated at three approved emicizumab dosing regimens (once a week, once every 2 weeks and once every 4 weeks) across two transition scenarios: last dose of emicizumab given on the day of valoctocogene roxaparvovec infusion versus last dose of emicizumab administered 4 weeks post-infusion. Haemostatic control was maintained regardless of emicizumab dosing regimen or scenario, suggesting that several approaches can safely transition patients from emicizumab prophylaxis to valoctocogene roxaparvovec gene therapy in the clinic.&lt;/p&gt;&lt;p&gt;An algorithm was subsequently presented to guide the timing of emicizumab discontinuation when transitioning to gene therapy. The authors suggested that FVIII activity levels should be evaluated 4 weeks post-valoctocogene roxaparvovec infusion. If FVIII is ≥ 5 IU/dL at Week 4 and remains ≥ 5 IU/dL at Week 5, discontinuation of emicizumab can be considered. If FVIII activity is &lt; 5 IU/dL at Week 4, prescribers should consider continuing emicizumab prophylaxis until two consecutive weekly measurements of ≥ 5 IU/dL are achieved.&lt;/p&gt;&lt;p&gt;Here, we present details of our real-world clinical experience of transitioning an adult male patient with severe haemophilia","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 5","pages":"1247-1249"},"PeriodicalIF":3.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.15086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970960","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":"Factor V haemostatic diathesis impairing thrombin activation, membrane binding and circulating antigen level due to a novel compound heterozygous mutation, Leu1821Ser and Gly2192Cys","authors":"Kimberley Talbot,&nbsp;Jina Song,&nbsp;John R. Perrier,&nbsp;Shannon Jackson,&nbsp;Ross T. A. MacGillivray,&nbsp;Edward L. G. Pryzdial","doi":"10.1111/hae.15087","DOIUrl":"10.1111/hae.15087","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Congenital factor V (FV) deficiency is a rare clotting disorder affecting ∼1 in 1,000,000, with bleeding severity that ranges broadly for poorly understood reasons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To help understand the molecular basis of the observed phenotype in FV deficient patients, the genetics and biochemistry causing a patient's FV deficiency were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>A 71-year-old female, who had serious life-long bleeding upon provocation and profound menorrhagia that lead to hysterectomy, was found to have 3% of normal plasma FV antigen with normal electrophoretic mobility. Platelet FV was similarly low, although the banding pattern was less fragmented than normal. Plasma clotting activity was &lt;1% of normal. Familial inheritance and DNA sequence analysis from peripheral blood leukocytes were consistent with novel compound heterozygosity with missense mutations in exon XVII, Leu1821 to Ser (L1821S) and exon XXV, Gly2192 to Cys (G2192C). The respective single-mutation variants were expressed and purified. Explaining why the antigen level and activity were inequivalent, thrombin activation of recombinant (<i>r</i>) FV/L1821S was impaired, and rFV/G2192C was unable to bind to a procoagulant phospholipid membrane.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings are consistent with the observed phenotype, highlighting the importance of understanding FV biochemical function to rationalize clinical bleeding severity when the circulating antigen level is discordant.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"30 5","pages":"1170-1176"},"PeriodicalIF":3.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.15087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906403","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}