Haemophilia最新文献

{"title":"The Use of Primary Care Physiotherapy for Persons With Bleeding Disorders in the Netherlands-A Retrospective Study of Health Records.","authors":"Johan Blokzijl, Martijn F Pisters, Cindy Veenhof, Roger E G Schutgens, Merel A Timmer","doi":"10.1111/hae.70034","DOIUrl":"https://doi.org/10.1111/hae.70034","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with musculoskeletal complaints as a result of their bleeding disorder can benefit from primary care physiotherapy. The current study aims to describe physiotherapy services provided in primary care to patients with bleeding disorders and to what extent treatment was already in concordance with treatment recommendations as published in a clinical practice guideline in April 2024.</p><p><strong>Methods: </strong>Researchers collected data from medical notes of primary care physiotherapists in the Netherlands treating a patient with a bleeding disorder. Collected data included; patient characteristics, condition for which treatment was initiated, total number of sessions, treatment modalities provided and outcome of treatment. Data from medical files was compared with 19 treatment recommendations stated in the newly developed clinical practice guideline.</p><p><strong>Results: </strong>Data from 86 treatment episodes of 62 patients by 52 different physiotherapists was collected. Treatment episodes were initiated for haemophilic arthropathy (n = 47), joint bleed (n = 24), muscle bleed (n = 9) and synovitis (n = 6). The most frequently provided treatment modalities included manual techniques (in haemophilic arthropathy) and exercise therapy (in all other conditions). The percentage in which treatment was in concordance with the recommendation ranged between 17% and 100%.</p><p><strong>Conclusion: </strong>The study indicated that exercise therapy was a commonly used treatment modality for all conditions. In contrast with other conditions, manual techniques were a frequently provided treatment modality in haemophilic arthropathy. Treatment was in many instances not in concordance with newly developed treatment recommendations. Dissemination and implementation of the recently developed treatment recommendations have the potential to improve primary care physiotherapy treatment for persons with bleeding disorders.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656938","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":"Bone Health Screening in Persons With Bleeding Disorders: A Survey of United States Haemophilia Treatment Centres.","authors":"Divyaswathi Citla-Sridhar, Sanjay Ahuja, Robert Sidonio, Meera Chitlur, Anjali Sharathkumar, Patricia Tobase, Suchitra Acharya, Daniel Isaac, Roshni Kulkarni, Marilyn Manco Johnson","doi":"10.1111/hae.70027","DOIUrl":"https://doi.org/10.1111/hae.70027","url":null,"abstract":"<p><strong>Background: </strong>Despite reports of elevated rates of osteoporosis and fractures in persons with haemophilia (PwH) and von Willebrand disease (PwVWD), routine bone health screening using dual-energy X-ray absorptiometry (DEXA) scans is not consistently implemented for this population across all Haemophilia Treatment Centres (HTCs) in the United States.</p><p><strong>Objectives: </strong>The primary aim of this study was to examine rates of screening for bone health in PwH and PwVWD with vitamin D levels and DEXA scans.</p><p><strong>Methods: </strong>We conducted a survey of all federally funded HTCs nationwide from June 2023 to August 2023. Nine multiple-choice questions were developed to explore the roles of HTC providers and their current practices for bone health assessment.</p><p><strong>Results: </strong>The survey achieved a response rate of 44.8% (66 out of 147 HTCs). Among the responding centres, 21 HTCs (31.8%) reported routinely screening for vitamin D deficiency during annual comprehensive visits, while 13.6% (n = 9) performed regular bone health screenings using DEXA scans. Of these nine centres, three were adult HTCs and six were lifespan HTCs. DEXA scans were ordered either by physicians at the HTC (n = 5, 55.5%) or patients were referred to primary care providers, endocrinologists, or other specialists (n = 4, 44.4%). The top three indications for DEXA scans among the responding HTCs included HIV (n = 7, 77.7%), low physical activity or immobility (n = 6, 66.7%), fractures after a minor fall or injury in patients under 50 years of age (n = 5, 55.5%) and vitamin D deficiency (n = 5, 55.5%). These findings underscore the need for specific standardized screening guidelines to optimize bone health screening in PwH and PwVWD.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572796","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":"Inhibitor Eradication in Postpartum Acquired Haemophilia A: Real-Life Case Series and Literature Review.","authors":"Gaetano Giuffrida, Uros Markovic, Stephanie Grasso, Andrea Duminuco, Gabriella Santuccio, Manlio Fazio, Giuliana Giunta, Lara Gullo, Chiara Sorbello, Sara Frazzetto, Salvatore La Penta, Mariasanta Napolitano, Gianluca Sottilotta, Francesco Di Raimondo, Gabriele Sapuppo","doi":"10.1111/hae.70020","DOIUrl":"https://doi.org/10.1111/hae.70020","url":null,"abstract":"<p><strong>Background: </strong>Acquired haemophilia A (AHA) is a rare and severe bleeding disorder generally associated with pregnancy or aging. Spontaneous remission and prompt inhibitor eradication are described more frequently in postpartum cases. We evaluated retrospectively 15 postpartum AHA cases between 2007 and 2023 in order to evaluate response in terms of inhibitor eradication.</p><p><strong>Results: </strong>The median age at diagnosis was 31 years (range 24-38). All patients reported bleeding at presentation after a median period of 40.6 days following delivery (range 2-180 days). The median FVIII level was 4.4% (range 0%-12.8%), with a median FVIII-inhibitor titer of 35 BU (range 2-156). The most severe bleeding symptoms were metrorrhagia and genital bleeding in nine patients (60%), and one patient had an important muscular haematoma. Two patients underwent hysterectomy before diagnosis due to severe bleeding. All patients required anti-haemorrhagic therapy with a median duration of 8 days (range 1-28 days): 60% (9/15) with eptacog alfa, two with an activated prothrombin complex concentrate, and in combination in four cases. The immunosuppressive treatment was corticosteroids alone in eight patients (53%), cyclophosphamide or azathioprine in combination with corticosteroids in four, while rituximab was used in two cases following traditional immunosuppressive therapy. After a median period of 28 days (range 10-210 days), the anti-FVIII inhibitor was eradicated with normalisation of coagulation in all but one patient. However, immunosuppressive therapy, including tapering, had a median duration of 2.3 months (range 1-23 months). At the time of data censoring, all patients were alive and well at the last follow-up with no significant adverse events.</p><p><strong>Summary/conclusion: </strong>Notwithstanding that postpartum AHA has been reported to have a high rate of spontaneous remission, nearly half of this series experienced inhibitor eradication more than 1 month after disease onset and using immunosuppressive treatment for more than 2 months, with additional drugs being used in more than 40% of them, thus showing difficulties in disease remission in this postpartum AHA subpopulation.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572798","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":"Ratio of Von Willebrand Collagen Binding Assay and Von Willebrand Antigen Can Predict Multimer Size in Von Willebrand Disease.","authors":"Adrian Kimiaei, Iva Pruner, Maria Farm, Margareta Holmström, Natali Karandyszowska, Maria Bruzelius, Jovan Antovic, Anna Ågren","doi":"10.1111/hae.70025","DOIUrl":"https://doi.org/10.1111/hae.70025","url":null,"abstract":"<p><strong>Background: </strong>Von Willebrand disease (vWD) is a common bleeding disorder with different subtypes. Laboratory diagnosis is challenging, involving several expensive and complex assays. The von Willebrand factor (vWF) collagen binding assay (VWF:CB) has been described to improve the diagnosis of vWD, but there is a lack of consensus and its implementation into guidelines and diagnostic algorithms is incomplete.</p><p><strong>Methods: </strong>A cohort of 88 patients with inherited vWD and 10 patients investigated for vWD due to a bleeding phenotype were recruited and underwent analysis of vWF multimers, vWF antigen (VWF:Ag) and VWF:CB. The total bleeding score (BS) was calculated by using the bleeding assessment tool recommended by the International Society on Thrombosis and Haemostasis. An optimal VWF:CB/VWF:Ag ratio cutoff for differentiating between patients with all multimer sizes and those lacking high molecular weight multimers (HMWM) was established, and the findings were validated in a separate retrospective clinical data cohort. The association between VWF:CB/VWF:Ag ratio and BS was also assessed.</p><p><strong>Results: </strong>VWF:CB/VWF:Ag ratio was a very good discriminator of HMWM presence, yielding a sensitivity of 1.0 and a specificity of 0.79 at the optimal cutoff in the validation dataset. VWF:CB/VWF:Ag ratio was a significant predictor of BS (R² = 0.39).</p><p><strong>Conclusion: </strong>VWF:CB/VWF:Ag ratio is a significant predictor of BS and multimer analysis can be safely omitted in patients with vWD and a VWF:CB/VWF:Ag ratio above 0.6, confirming the VWF:CB assay as an important contributor to vWD diagnosis.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572799","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":"Exploring the Impact of Laboratory Reagents on Pharmacokinetic Profiling.","authors":"Pierre Chelle, Dagmar Hajducek, Emma Iserman, Alfonso Iorio, Andrea Edginton","doi":"10.1111/hae.70021","DOIUrl":"https://doi.org/10.1111/hae.70021","url":null,"abstract":"<p><strong>Background: </strong>Laboratory reagents impact measured factor activity of extended half-life (EHL) concentrates. Variability in measurements may lead to under or over estimation of the pharmacokinetic (PK) parameters, and thus influence clinical dosing decisions. Since 2020, WAPPS-Hemo (www.wapps-hemo.org) has been collecting reagent information when haemophilia centres submit data for PK parameters estimation.</p><p><strong>Objectives: </strong>To identify the pairs of concentrates (recombinant FVIII and FIX) and reagents leading to significant discrepancies between observed PK estimates compared to WAPPS-Hemo population.</p><p><strong>Methods: </strong>PK data were extracted from the WAPPS-Hemo database. PK estimates were obtained using WAPPS-Hemo Bayesian engine and analysis was reported for terminal half-life and time to 3% following a 50 IU/kg infusion. Log-deviations between individual PK estimates and WAPPS-Hemo population PK models typical values were calculated to remove known sources of variability. Multivariate analysis of variance (MANOVA) regression was performed to assess the reagent effects.</p><p><strong>Results: </strong>A total of 3853 and 1312 PK estimates were used to analyse reagent effects on the four FVIII and three FIX EHL concentrates, respectively. The reagent was not provided for 2391 PK estimates (46.3%). WFH unadvised reagents were provided for 78 PK estimates only (2.8% of known reagents). For each concentrate/reagent pair recommended by WFH, no significant difference was identified, except for rFIX-Fc whose PK parameters were significantly and clinically under-estimated by STA PTT-A.</p><p><strong>Discussion/conclusion: </strong>Real-world data provided by haemophilia centres showed high congruence with WFH guidelines, although its sizable number not declaring reagent. WFH-recommended reagents did not significantly impact PK estimation. For rFVIII-PEG, reagents also did not impact PK estimation. Although usually not enough data were available to assess reagents that were unadvised by WFH.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572797","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":"High Prevalence of Platelet Function Disorders in Women Referred for Surgical Management of Refractory Heavy Menstrual Bleeding.","authors":"Alison Delaney, Evangelos I Kritsotakis, Kevin Horner, Steve Kitchen, Jennifer Sedcole, Ted Baxter, Rhona M Maclean, Michael Makris, Clare V Samuelson","doi":"10.1111/hae.70016","DOIUrl":"https://doi.org/10.1111/hae.70016","url":null,"abstract":"<p><strong>Introduction: </strong>Heavy menstrual bleeding (HMB) is a common presenting symptom in women with bleeding disorders, yet haemostatic testing is sometimes overlooked, even when refractory HMB requires surgical intervention.</p><p><strong>Aim: </strong>To determine the prevalence of bleeding disorders in women referred for surgical management of HMB and investigate screening approaches for bleeding disorders in this population.</p><p><strong>Methods: </strong>Women with refractory HMB referred for surgical management were enrolled prospectively and underwent a detailed haemostatic investigation. The International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT) and PFA-100 assay were interrogated as screening tools for bleeding disorders. Multiplate whole blood impedance aggregometry (WBIA) was compared to the current gold-standard lumiaggregometry testing for platelet dysfunction.</p><p><strong>Results: </strong>Fifty women underwent laboratory testing. Sixteen percent (95% confidence interval [CI] 7.2%-29.1%) were diagnosed with platelet function defects based on persistently abnormal lumiaggregometry results. No other clinically significant abnormalities were diagnosed. Women were more likely to be diagnosed with platelet dysfunction if they had failed a greater number of prior therapies, particularly prior endometrial ablation. The ISTH-BAT lacked diagnostic accuracy, even at the calculated optimal cutoff value, and PFA-100 assay lacked sensitivity. Multiplate WBIA was inferior to lumiaggregometry for the detection of platelet function disorders, with sensitivity of 62.5% (95% CI 24.5%-91.5%) and specificity of 87.5% (95% CI 73.2%-95.8%).</p><p><strong>Conclusion: </strong>Study findings support platelet function analysis by lumiaggregometry in women with refractory HMB requiring surgery. Accurate diagnosis would allow targeted haemostatic therapy and implementation of additional perioperative safety measures if surgery is still required.</p>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536988","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":"Systematic Literature Review of Outcomes Associated With Adherence to Haemophilia Drug Therapy","authors":"Cynthia Khanji,&nbsp;Weyinmi Nuabor,&nbsp;Travis Gould,&nbsp;Hae Kyung Kim,&nbsp;Stephanie Barrows,&nbsp;Brittney Herbel,&nbsp;Annete Njue","doi":"10.1111/hae.15153","DOIUrl":"10.1111/hae.15153","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Prophylactic therapy improves clinical and quality of life (QoL) outcomes in patients with haemophilia; however, this effect could be influenced by the degree of treatment adherence. Adherence to therapy may be difficult due to the administration mode and the frequency of self-infusions. There is a need to investigate the effect of treatment adherence on clinical, humanistic and economic outcomes in a real-world setting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>A systematic literature review (SLR) was performed to describe the impact of adherence to haemophilia drug therapies on clinical, humanistic and economic outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Embase, MEDLINE and the Cochrane Library were searched for English language articles published after 22 June 2013; the search was conducted on 22 June 2023. No geographic limits were applied. Twenty articles met the inclusion criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The studies investigated associations between treatment adherence and bleeding, joint health, inhibitor development, pain, QoL, daily activity/work productivity (WP), cognitive function and healthcare resource use. Fifteen studies reported that better adherence to drug therapy in patients with haemophilia is associated with better outcomes, including a reduction in bleeding risk, improved joint structure and function, less chronic pain, better health-related QoL (HRQoL), lower activity impairment (AI), less school/work absenteeism, higher WP and better cognitive function. Two studies reported mixed results, with adherence being associated with some outcomes but not others. Five studies reported no association.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This SLR found associations between greater adherence to haemophilia drug therapies and better results on clinical, humanistic and economic outcomes, indicating that patients with haemophilia would benefit from improvements in treatments that promote adherence.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 2","pages":"187-206"},"PeriodicalIF":3.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.15153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491752","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 Systematic Joint Examination (Ultrasound, Functional and Physical) on Treatment Management Decisions in Patients With Haemophilia A in France: Final Data From the Prospective, Observational A-MOVE Study","authors":"Nicolas Drillaud,&nbsp;Virginie Barbay,&nbsp;Jean Baptiste Valentin,&nbsp;Romain Jailler,&nbsp;Aurélien Lebreton,&nbsp;Brigitte Pan-Petesch,&nbsp;Sabine Marie Castet,&nbsp;Birgit Frotscher,&nbsp;Laurent Frenzel,&nbsp;Sandrine Jousse-Joulin,&nbsp;Hervé Chambost,&nbsp;Mikaela Alenäs,&nbsp;Markus Fusser,&nbsp;Corinne Gandossi,&nbsp;Meriem Zidi,&nbsp;Oussama Mahdout,&nbsp;Yohann Repessé,&nbsp;the A-MOVE study group","doi":"10.1111/hae.70012","DOIUrl":"10.1111/hae.70012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Haemophilia management aims to prevent bleeding and preserve joint function. Changes in patients’ joint health may influence physicians' decisions to adjust treatment. The Haemophilia Joint Health Score (HJHS) and Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) score assess joint health but are not routinely used.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To evaluate whether systematic joint examination with HJHS and/or HEAD-US had an impact on treatment management decisions in France, using final data from the A-MOVE study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A-MOVE (NCT04133883) was a 12-month prospective, multicentre study, which enrolled persons with haemophilia A (all severities, aged 6–40 years) treated prophylactically or on demand with standard/extended half-life FVIII replacement. At baseline, 6 and 12 months, HJHS/HEAD-US and changes in patients’ management were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eighty-six patients from 20 sites were included in the final analysis; 68 had HJHS/HEAD-US assessments at 12 months. Over 12 months, 24.4% (<i>n</i> = 21/86) of patients experienced an impact on their haemophilia management due to HJHS/HEAD-US scores; these decisions were impacted by HJHS in about half of the patients (52.4%, <i>n</i> = 11/21) and HEAD-US in almost all patients (95.2%, <i>n</i> = 20/21). Both assessments contributed to a change in management decisions in about half of the patients (47.6%, <i>n</i> = 10/21). Twenty-nine patients (33.7%) had haemophilia management decisions impacted by factors other than HJHS/HEAD-US, including physical examination findings (<i>n</i> = 9) and the occurrence of bleeding episodes (<i>n</i> = 8).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Final data from the A-MOVE study show that systematic joint assessments, through functional/physical examination (HJHS) and ultrasound (HEAD-US), may impact treatment management decisions in persons with haemophilia A.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 2","pages":"239-246"},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491750","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 a Single-Tube Reverse Transcription Real-Time PCR Assay for Diagnosis of F8 Intron 22 Inversion in Patients and Carriers of Haemophilia A","authors":"Javier Arzuaga-Mendez,&nbsp;Lucia Insunza,&nbsp;María José Ojinaga,&nbsp;Ana Moretó,&nbsp;Maite Moreno-Gamiz,&nbsp;Miriam Vara-Pampliega,&nbsp;Juan Carlos Garcia-Ruiz,&nbsp;Cristina Sierra-Aisa","doi":"10.1111/hae.70014","DOIUrl":"10.1111/hae.70014","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Intron 22 inversion mutation of F8 (inv22) is the most frequent cause of Haemophilia A (HA) and is present in approximately 45% of severe HA cases. This mutation disrupts <i>F8</i> gene continuity, leading to a truncated protein. Traditional methods for detecting inv22, including inverse-shifting PCR and long-range PCR, are accurate but labour-intensive. F8 inv22 truncated mRNA transcript contains a short (51 base pairs) abnormal exon 23. Thus, reverse-transcription PCR has been proposed for the diagnosis of inv22 in patients with HA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The aim of this study was to design and validate a multiplex reverse-transcription real-time PCR (RT-qPCR) assay capable of detecting and differentiating between normal and inv22 F8 transcripts in a single reaction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We designed an RT-qPCR assay that employs specific primers and TaqMan probes to detect the exon 22 to 23 junction present in the normal F8 transcript, and the junction between exon 22 and the abnormal sequence only present in F8 transcripts harbouring inv22. We tested our assay in 14 HA patients (six with inv22 and eight with other mutations), four HA female carriers (two with inv22 and two with other mutations), and six negative controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>F8</i> expression in peripheral blood RNA was sufficient to be detected by RT-qPCR. The assay showed perfect concordance within the cohort to identify inv22 in both patients and carriers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>RT-qPCR is an accurate method for diagnosing inv22 in patients and HA carriers. Moreover, it is simpler and faster than previous methods.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":"31 2","pages":"263-268"},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491627","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":"American Thrombosis and Hemostasis Network: National Bleeding Disorders Foundation Data Commons: Better Together.","authors":"Tammuella E Chrisentery-Singleton, Philip M Gattone, Christine M Gerber, Kevin D Mills, Moses E Miles, Dawn Rotellini, Maria E Santaella, Leonard A Valentino, Crystal Watson, Michael Recht","doi":"10.1111/hae.70011","DOIUrl":"https://doi.org/10.1111/hae.70011","url":null,"abstract":"","PeriodicalId":12819,"journal":{"name":"Haemophilia","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472446","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}