Haemophilia最新文献

{"title":"Male Range of Motion Norms in the Haemophilia Joint Health Score Underrepresent the Severity of Joint Damage in Females","authors":"Maria Barrett,&nbsp;Laura Singer-Fox,&nbsp;Dianne Thornhill,&nbsp;Joanna Roybal,&nbsp;Beth Boulden Warren","doi":"10.1111/hae.70346","DOIUrl":"10.1111/hae.70346","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Joint bleeding causes haemarthropathy, impacting quality of life. Joint outcomes research in bleeding disorders has focused on males; however, females are also affected. The Haemophilia Joint Health Score (HJHS) is a validated physical exam measure of haemarthropathy, which includes flexion and extension loss parameters derived from male range of motion (ROM) norms. Female ROM norms are not included in the HJHS instruction manual.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To determine whether using female ROM norms, rather than standard male ROM norms, yields revised HJHS values in females with bleeding disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Participants assigned female at birth with bleeding disorders and clinical HJHS exams at the University of Colorado were included in analysis. HJHS was calculated by standard methods, including flexion and extension loss measures comparing joint angles to the contralateral side and to normative male and female ROM angles. The frequency and magnitude of Score Revisions when applying female ROM norms were calculated and compared across individual joints (ankle, knee, elbow), joint pairs, and participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The analysis included 187 females with 448 HJHS exams. At least 1 Score Revision occurred when applying female ROM norms in 92/187 participants (49.2%) across 184/448 exams (41.1%). When using the female rather than male ROM norms, the 6-joint total HJHS revision was 0.67 ± 1.29 (mean ± standard deviation) points higher (<i>p</i> &lt; 0.001). Applying male ROM norms underestimated the total HJHS in 136 (33.8%) exams. Ankles joints were most frequently underestimated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Applying male ROM values to HJHS calculations in females with bleeding disorders underestimates haemarthropathy, particularly in the ankle.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"32 5","pages":"1222-1228"},"PeriodicalIF":3.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148375447","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":"Plasma-Derived Factor VIIa/Factor X Improves Thrombin Generation Potential in a Plasma Model of Haemophilia A Supplemented With Direct Oral Anticoagulants.","authors":"Shigeharu Oh, Yuto Nakajima, Tomoko Onishi, Eisuke Takami, Hirotoshi Nakano, Keiji Nogami","doi":"10.1111/hae.70402","DOIUrl":"https://doi.org/10.1111/hae.70402","url":null,"abstract":"<p><strong>Background: </strong>Patients with haemophilia (PwH) complicated with atrial fibrillation require direct oral anticoagulants (DOACs) to prevent thrombosis, but still require haemostatic management to control bleeding. However, specific recommendations for managing bleeding in PwH with inhibitors (PwH-inh) receiving DOACs remain lacking. In Japan, plasma-derived (pd-) factor (F)VIIa/FX products are available for clinical management of PwH-inh, and may also be beneficial for haemostatic treatment in PwH-inh receiving DOACs.</p><p><strong>Aim: </strong>To assess coagulation potential of pd-FVIIa/FX or other bypassing agents (BPAs) using an in vitro plasma model of PwHA-inh receiving DOACs.</p><p><strong>Methods: </strong>FVIII-deficient plasma was preincubated with anti-FVIII inhibitor (termed 'FVIII-depleted'). Pd-FVIIa/FX (1.5 µg/mL as FVIIa), recombinant (r)FVIIa (2.2 µg/mL), activated prothrombin complex concentrates (aPCC; 1.3 IU/mL), or FX preparation (520 nM) were added to FVIII-depleted plasmas supplemented with apixaban (100 ng/mL) or edoxaban (100 ng/mL). A similar model was prepared using plasma samples spiked with emicizumab (50 µg/mL). Coagulation potential was assessed utilizing thrombin generation assay (TGA).</p><p><strong>Results: </strong>The addition of pd-FVIIa/FX to FVIII-depleted plasmas supplemented with DOACs increased TG potential to near-normal range, irrespective of the presence of emicizumab. However, the addition of rFVIIa or FX alone to the FVIII-depleted plasma with DOACs exhibited coagulation potential below the normal range. The addition of aPCC and emicizumab to FVIII-depleted plasmas with DOACs enhanced TG potential above the normal range.</p><p><strong>Conclusion: </strong>Pd-FVIIa/FX improved coagulation potential in the in vitro model plasma of PwHA-inh spiked with DOACs, irrespective of concomitant emicizumab. The clinical efficacy and safety of pd-FVIIa/FX require further evaluation.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911781","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":"Venous and Arterial Thrombo-Embolic Events in Patients With von Willebrand Disease From Western France: The TWIGO Study","authors":"Agnès Granottier,&nbsp;Kilian Trin,&nbsp;Sara Robin,&nbsp;Marc Trossaert,&nbsp;Laurent Ardillon,&nbsp;Damien Tabaux,&nbsp;Johann Rose,&nbsp;Philippe Beurrier,&nbsp;Benoît Guillet,&nbsp;Imane Aoubiza,&nbsp;Morgane Pierre-Jean,&nbsp;Yohann Repesse,&nbsp;Claire de Moreuil,&nbsp;Brigitte Pan-Petesch","doi":"10.1111/hae.70309","DOIUrl":"10.1111/hae.70309","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Patients with von Willebrand disease (VWD) are prone to bleeding, yet they may also experience thrombotic events, whose nature, frequency, and optimal management remain poorly characterised.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To describe the nature and frequency of venous and arterial thrombotic events in VWD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This multicentre retrospective study analyzed thrombotic events in 1345 patients with constitutional VWD and von Willebrand factor (VWF) activity ≤30 IU/dL from the French BERHLINGO database. Venous events included deep vein thrombosis (DVT) and pulmonary embolism (PE); arterial events included angina, myocardial infarction (MI), ischaemic stroke (ICVA), transient ischaemic attack (TIA), and peripheral artery disease (PAD). Risk factors, therapeutic strategies, efficacy, and bleeding complications were also assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 35 thrombotic events: 30 arterial (12 angina, 6 MI, 7 PAD, 4 ICVA, 1 TIA) in 20 patients, and 5 venous (3 PE±DVT, 2 DVT) in 4 patients (1.8% prevalence). The mean patient age was 61.8±14 years. Most arterial events (70%) occurred in men; all venous events were provoked in women. Therapeutic adjustments were made for 10 arterial events (28.6%: 4 withholding, 6 low-dose). Of the 35 events, 11 (31.4%) were recurrences (second or subsequent) in the same patient. Overall, 8/24 patients (33.3%) had multiple events, always at the same site, including twice (18.2%) after therapeutic adjustments. Only trauma-induced bleeding was reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although rare, thrombosis in VWD patients is associated with age and gender. Given the low bleeding risk, therapeutic approaches similar to those in the general population may be considered.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>Cardiovascular and Venous Thromboembolism Disease in Patients with Von Willebrand Disease in the French West (TWIGO); ClinicalTrials.gov ID NCT05773638</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"32 5","pages":"1208-1221"},"PeriodicalIF":3.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148137904","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":"Responsiveness and Minimal Important Change of the Haemophilia Activities List in Patients With Inherited Bleeding Disorders","authors":"Johan Blokzijl,&nbsp;Isolde A. R. Kuijlaars,&nbsp;Martijn F. Pisters,&nbsp;Cindy Veenhof,&nbsp;Janjaap van der Net,&nbsp;Roger E. G. Schutgens,&nbsp;Kathelijn Fischer,&nbsp;Merel A. Timmer","doi":"10.1111/hae.70327","DOIUrl":"10.1111/hae.70327","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The Haemophilia Activities List (HAL) is a disease-specific patient-reported outcome measure (PROM) that is widely used in both healthcare and research in people with inherited bleeding disorders (PWBD), but information on responsiveness and minimal important change (MIC) is lacking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The aim of this study is to determine the responsiveness and MIC of the HAL to measure self-reported limitations in activities in PWBD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PWBD on the waiting list for orthopaedic surgery were invited to participate. Participants completed the HAL, reference PROMs regarding pain, physical functioning and ADL activities at baseline, 3 months and 12 months after surgery. The general perceived effect was completed at 3 and 12 months after surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 32 surgeries performed in 28 participants were included. Three months after surgery the change of the HAL sum score showed moderate to strong correlation with the change on the physical functioning PROMs (<i>r: 0.56)</i> and the change on the ADL PROMs (<i>r: 0.65)</i> and weak correlation with pain scores. The HAL was well able to discriminate participants that improved in self-reported limitations in activities and participation from those that did not improve (AUC: 0.86 (95%CI: 0.71–1.0)). The MIC_improvement was −2.3 (95%CI: −6.0;1.4) and the MIC_{deterioriation} −4.9 (95%CI: −8.4;−2.5).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>As the MIC is smaller than the smallest detectable change (SDC) of the HAL, it can be assumed that if a person has improved or deteriorated more than the known SDC of 10.2 (previous research), they are likely to experience a meaningful change over time.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"32 5","pages":"1247-1254"},"PeriodicalIF":3.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.70327","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148137885","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":"Optimizing Emergency Department Care for People With Bleeding Disorders: A Scoping Review of Barriers and Interventions for Improvement","authors":"Ling-Yi Guo,&nbsp;Diane L. Lorenzetti,&nbsp;Natalia Rydz,&nbsp;Dawn Goodyear,&nbsp;Julia Hews-Girard,&nbsp;Garrick Mok,&nbsp;Roy Khalife,&nbsp;Kelsey Uminski","doi":"10.1111/hae.70334","DOIUrl":"10.1111/hae.70334","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Emergency department (ED) care is critical for managing acute bleeding events in people with bleeding disorders. Despite international guidelines recommending haemostatic treatment within 30–60 min, delays and deviations from best practices are common and associated with poorer outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Identify barriers to guideline-concordant ED management of bleeding disorders, evaluate interventions, assess clinical impact, and highlight knowledge gaps to inform future research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Five databases (MEDLINE, Embase, Scopus, Web of Science, Cochrane Library) were searched from inception to 21 March 2025, following established scoping review guidelines and a pre-registered protocol. Eligible studies examined barriers or interventions for improving ED care. Data were independently screened and extracted by two reviewers, then synthesized using descriptive statistics and narrative synthesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventeen studies out of 3541 met inclusion criteria. Common barriers included electronic medical record (EMR) limitations, absence of standardized protocols, limited healthcare professional education, and inadequate communication with haematology. Delayed time to therapy (<i>n</i> = 8, range 1.4–5.6 h) was frequently reported; additional impacts included failure to administer haemostatic therapy for confirmed/suspected bleeding, non-indicated diagnostic testing, and patient mortality. Most interventions combined EMR enhancements with education. All interventions were associated with improved outcomes, including reduced time to therapy (<i>n</i> = 4, range 0.4–2.5 h). Perspectives of people with bleeding disorders and caregivers were infrequently incorporated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This review provides the first comprehensive synthesis of barriers and interventions in ED care for people with bleeding disorders, identifying critical gaps in timely treatment, interdisciplinary coordination, and stakeholder engagement. These findings provide a foundation for future quality improvement research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"32 5","pages":"1135-1159"},"PeriodicalIF":3.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.70334","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251301","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":"Management of Breakthrough Bleeding During Emicizumab Prophylaxis in Acquired Haemophilia A: Data From the GTH-AHA-EMI Study","authors":"Halet Türkantoz,&nbsp;Christiane Dobbelstein,&nbsp;Richard Greil,&nbsp;Christina Hart,&nbsp;Robert Klamroth,&nbsp;Paul Knöbl,&nbsp;Johannes Oldenburg,&nbsp;Christian Pfrepper,&nbsp;Ulrich Sachs,&nbsp;Inga M. Schimansky,&nbsp;Karolin Trautmann-Grill,&nbsp;Andreas Tiede","doi":"10.1111/hae.70339","DOIUrl":"10.1111/hae.70339","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The GTH-AHA-EMI study showed that emicizumab reduces bleeding in patients with acquired haemophilia A (AHA). However, 22 clinically relevant new bleeds (CRNB) occurred in 14 of the 47 study patients, most of which required haemostatic treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To describe characteristics, treatment, and outcome of CRNB that occurred during the 12 weeks of haemostatic prophylaxis with emicizumab.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were extracted from the GTH-AHA-EMI study data base. Further information was collected retrospectively using a standardized questionnaire answered by study investigators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 22 CRNB, 9 and 13 were classified as major and non-major, respectively. 15 bleeds occurred spontaneously, and 20 bleed required treatment. Recombinant factor VIIa was used for treatment in 16 of 20 treated bleeds, recombinant porcine factor VIII was used in three events. Eight patients were admitted to the hospital because of CRNB; extension of hospitalization was reported in 13 patients; 9 were admitted to an intensive care unit; invasive interventions were required in nine patients. Most bleeds were treated successfully; permanent harm from bleeding was reported in two patients. No thromboembolic events or other adverse events were reported.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although emicizumab reduces bleeding in AHA, breakthrough bleeding can still occur, was often severe and required haemostatic treatment. Haemostatic treatment was safe and usually effective.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>NCT04188639</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"32 5","pages":"1188-1199"},"PeriodicalIF":3.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.70339","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251298","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":"Utilisation and Perceived Value of Genetic Counsellors Within US Haemophilia Treatment Centres","authors":"Caylynn Carls,&nbsp;Sumedha Ghate,&nbsp;Stefanie N. Dugan,&nbsp;Radhika N. Sawh,&nbsp;DeBran A. Tarver","doi":"10.1111/hae.70340","DOIUrl":"10.1111/hae.70340","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Rapid advancement of molecular genetics has transformed the diagnosis, treatment, and management of individuals with hereditary bleeding disorders. To provide effective, up-to-date genetic counselling, navigate the complexity of these conditions, and select appropriate molecular testing, genetics expertise is required.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study assessed the provision of genetic counselling services, involvement of genetic counsellors (GCs), and the perceived value of GCs within haemophilia treatment centres (HTCs) in the United States.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A survey was emailed to 396 HTC providers. Of these, 115 responses were received, representing 68 of 149 US HTCs (45.6% HTC participation rate). Responses were stratified by level of GC engagement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Although GCs have extensive training in genetics, genomics and counselling skills, nearly one-third of respondents (34.9%, <i>n</i> = 38) reported that a GC is not involved with the HTC nor are referrals made. Almost all GC-engaged respondents (98%, <i>n</i> = 22) and GC-referral respondents (95%, <i>n</i> = 20) agreed that ‘GCs have a unique skill set that is highly valuable to an HTC clinic’ compared to only 62% (<i>n</i> = 20) of non-GC-engaged respondents (<i>p</i> = 0.001). Additionally, respondents noted positive implications of integrating a GC within their HTCs, stating that GCs are ‘ideal for optimal patient care’.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results highlight the value of a GC within an HTC. This signifies the need to reassess the role of GCs among HTCs to reduce inconsistencies in provision of genetic counselling and increase healthcare equity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"32 5","pages":"1229-1238"},"PeriodicalIF":3.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271217","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":"Preimplantation Genetic Testing for Families at Risk of Haemophilia: Ten-Year Single-Centre Experience","authors":"Mimosa Mortarino,&nbsp;Isabella Garagiola,&nbsp;Valeria Nicotra,&nbsp;Alessandra Riccaboni,&nbsp;Cristina Guarneri,&nbsp;Edgardo Somigliana,&nbsp;Flora Peyvandi","doi":"10.1111/hae.70358","DOIUrl":"10.1111/hae.70358","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Preimplantation genetic testing for monogenic diseases (PGT-M) is a reproductive option for couples at high risk of transmitting inherited disorders. We report a ten-year single-centre PGT-M experience in families at risk of hemophilia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A pre-clinical PGT-M work-up was performed for couples in which the female was a carrier of hemophilia A or B, following multidisciplinary counselling. Intracytoplasmic sperm injection (ICSI) was used to generate embryos. Blastocysts on days 5–7 were biopsied for genetic testing and cryopreserved by vitrification. Short tandem repeat markers were used for linkage analysis, alone or in combination with the pathogenic variant using a multiplex PCR. Embryos with conclusive results were transferred one at a time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>23 couples contacted the center seeking information on the PGT-M program, of which 19 underwent multidisciplinary counselling and pre-clinical PGT work-up. After ICSI, 69 embryos were biopsied and genetically characterized. A conclusive diagnosis was achieved for 58 embryos (84%): 42 unaffected embryos were suitable for transfer of whom 26 were transferred, resulting in 13 pregnancies (50% implantation rate per transfer), leading to eight live births, four miscarriages and one therapeutic termination. Prenatal diagnosis, performed in three cases, confirmed PGT-M results. Amplification failure occurred in nine cases, eight of which were successfully re-biopsied. Allele drop-out occurred in two embryos and recombination in one.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our experience shows that PGT-M is a valid and reliable option for couples at risk of transmitting severe genetic diseases, enabling prevention of affected pregnancies and reducing the emotional burden linked to therapeutic abortion.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"32 5","pages":"1239-1246"},"PeriodicalIF":3.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.70358","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148404636","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":"Assessment Tools for Adherence to Prophylactic Haemophilia Treatment in Adult and Adolescent Patients: A Systematic Review","authors":"Fadzlin Mohd Mokhtar,&nbsp;Sutha Rajakumar,&nbsp;Mark Cheong Wing Loong,&nbsp;Wei Lim Chong,&nbsp;Mohammed Magdy Hassanein,&nbsp;Hasniza Zaman Huri","doi":"10.1111/hae.70324","DOIUrl":"10.1111/hae.70324","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Prophylactic treatment offers greater clinical benefits than on-demand therapy for patients with haemophilia, but these benefits depend on sustained adherence. Although adherence assessment is essential for understanding treatment effectiveness, a wide range of tools is used, and their characteristics, scope, and limitations have not been systematically synthesized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This systematic review aimed to identify and critically appraise assessment tools used to measure adherence to prophylactic haemophilia treatment in adult and adolescent patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The protocol followed PRISMA-P guidelines and was registered with PROSPERO (CRD42021273813). We conducted a systematic search across multiple databases including PubMed, Ovid EMBASE, Web of Science, and Scopus for studies published between 2000–2022 that reported on adherence to prophylaxis in adolescents and adults with haemophilia. A narrative synthesis was used to summarise key themes, variations, and the strengths and limitations of the studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From the 22 studies, adherence was assessed using objective measures (prescription records), self-reported questionnaires, technology-assisted tools (electronic diaries and the Medtep Hemophilia online platform), and qualitative approaches. Self-reported questionnaires, particularly VERITAS-Pro and VERITAS-PRN, were the most frequently used adherence measures. Adherence assessment was frequently examined alongside medication supply and treatment practices, quality of life, bleeding episodes and haemarthrosis, joint health status, health beliefs and self-efficacy, environmental influences, and sociodemographic and clinical characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>VERITAS-Pro and VERITAS -PRN are central to the assessment of adherence to prophylactic haemophilia treatment. Their use alongside quality of life and illness perception measures supports clinical assessment and interpretation of adherence in both research and practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"32 5","pages":"1123-1134"},"PeriodicalIF":3.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101423","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":"An Ex Vivo Pharmacodynamic Study of KN057, a Tissue Factor Pathway Inhibitor Neutralizing Antibody, in Plasma Samples From Patients With Haemophilia or VWD3","authors":"Mankai Ju,&nbsp;Feng Xue,&nbsp;Wei Sun,&nbsp;Fang Li,&nbsp;Ting Xu,&nbsp;Renchi Yang","doi":"10.1111/hae.70331","DOIUrl":"10.1111/hae.70331","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Tissue factor pathway inhibitor (TFPI), a key regulator of tissue factor-initiated coagulation through FXa-dependent inhibition of the tissue factor-FVIIa complex, has emerged as a promising target for restoring thrombin generation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This ex vivo pharmacodynamic study aimed to evaluate the KN057, a novel humanized TFPI-neutralizing antibody, in plasma samples from participants with haemophilia or type 3 von Willebrand disease (VWD3).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this ex vivo spiking study, plasmas obtained from haemophilia or VWD3 participants were supplemented with KN057 at the concentration of 0–140.00 nM. The thrombin generation assay (TGA) and the dilute prothrombin time (dPT) assay were performed to assess coagulation responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Between 26, May 2021, and 3, September 2021, a total of 29 participants were enrolled in this study, including 10 haemophilia A (HA) without inhibitors, 6 haemophilia B (HB) without inhibitors, 6 HA with inhibitors, 3 HB with inhibitors, and 4 VWD3. In participant plasmas supplemented with KN057, peak thrombin and endogenous thrombin potential (ETP) increased notably between 1.12–5.60 nM, and reached a maximal level at 28.00 nM. A dose-dependent decrease in dPT was observed in all participants with haemophilia or VWD3.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>KN057 exhibited a consistent ex vivo pharmacodynamic profile, including both the response trend and effective concentration range, across plasma samples from patients with HA or HB, irrespective of inhibitor status. Furthermore, its pharmacodynamic activity in plasma from patients with VWD3 was comparable to that observed in haemophilia plasma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"32 5","pages":"1264-1271"},"PeriodicalIF":3.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.70331","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148156184","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}