Haemophilia最新文献_第10页

Development of the coreHEM mental health patient-reported outcome measure – A novel mental health outlook measure for people with haemophilia 核心 HEM 心理健康患者报告结果测量法的开发--针对血友病患者的新型心理健康展望测量法。

IF 3 2区医学 Q2 HEMATOLOGY

Haemophilia

Pub Date : 2024-09-05 DOI: 10.1111/hae.15085

Elizabeth Clearfield, Hsing-Yuan Chang, Ellen M. Janssen, Tabassum Majid, Donna A. Messner, Donna Coffin, Mohit Jain, Paul E. Monahan, Leonard A. Valentino, Michelle Witkop, Mark W. Skinner

Introduction

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.

Aim

To describe the methods used to develop a content validated patient-reported outcome measure (PROM) that measures MHO for people with haemophilia.

Methods

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.

Results

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).

Conclusions

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.

导言：目前，还没有一种生活质量工具能够全面反映血友病患者的心理健康前景（MHO）这一HEM核心结果，包括接受基因治疗的潜在转变体验。目的：描述用于开发内容经过验证的患者报告结果测量方法（PROM）的方法，该方法可测量血友病患者的心理健康前景：方法：根据文献/证据综述制定的概念框架用于创建访谈指南和起草调查问卷。15 岁或 15 岁以上患有重度/中度血友病的男性有资格参加概念激发或认知汇报访谈。在对概念激发访谈进行主题分析的基础上完善了概念框架，并根据概念框架制定了 PROM 项目。认知汇报会分两轮进行，优先考虑 PROM 的相关性和理解；项目反复更新：从 300 多个已确定的 MHO 概念中构建了一个包含五个领域（耻辱、焦虑、抑郁、生活干扰和身份认同）的概念框架。53 名参与者参加了访谈。经过 32 次概念激发访谈后，对框架进行了更新，增加了 8 个新的子概念，删除了 2 个子概念。问卷的更新包括项目的增删和措辞的改进。最终的核心 HEM MHO PROM 有 26 个问题，分为两个部分（与血友病相关的一般心理健康和基因治疗部分）：结论：该工具经过内容验证，可用作探索性结果。可以对 MHO 评分进行测量和比较，以便更深入地了解患者的生活质量。

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引用次数: 0

Determination of body composition by dual x-ray absorptiometry in persons with haemophilia 通过双 X 射线吸收测定法确定血友病患者的身体成分。

IF 3 2区医学 Q2 HEMATOLOGY

Haemophilia

Pub Date : 2024-09-01 DOI: 10.1111/hae.15091

Pia Ransmann, Marius Brühl, Jamil Hmida, Georg Goldmann, Johannes Oldenburg, Anna Christina Strauss, Thorsten Hagedorn, Frank Alexander Schildberg, Thomas Hilberg, Andreas Christian Strauss

Background

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.

Methods

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.

Results

Two hundred and one persons with mild (n = 44), moderate (n = 41), or severe (n = 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 (p = .474; p = .781). Persons with severe haemophilia had less lean mass compared to moderate and mild haemophilia (p = .013; p = .034). Total and appendicular fat is increased in older PwH (aged ≥40 years) compared to younger PwH (aged ≤29 years; p < .05). Lean mass did not differ between age groups.

Conclusion

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.

背景：有关血友病患者（PwH）身体成分的研究十分有限。文献描述，与健康对照组相比，血友病患者通过生物阻抗分析发现体内脂肪分布增加，瘦体重减少。双 X 射线吸收测量法（DXA）是已知的最精确的方法，本调查旨在根据血友病严重程度表型和年龄组推测身体成分参数的参考数据：方法：使用 Horizon 进行全身 DXA 筛查。方法：使用 Horizon 进行全身 DXA 筛查，评估体脂百分比、估计内脏脂肪组织（VAT）、附属脂肪和瘦体重，以及瘦体重和脂肪与身高的关系。对血友病严重程度和五个年龄组进行了区分：结果：共分析了 210 名轻度（44 人）、中度（41 人）或重度（116 人）血友病 A/B 患者（中位年龄为 40 [28-55; 1.IQ-3.IQ] 岁）。体脂率中位数为 28.7% [25.5%-33.9%]，估计增值税中位数为 657 g [403-954 g]，严重程度表型之间无显著差异（p = .474; p = .781）。与中度和轻度血友病患者相比，重度血友病患者的瘦体重较少（p = .013; p = .034）。老年血友病患者（年龄≥40 岁）的总脂肪和附属脂肪比年轻血友病患者（年龄≤29 岁；p 结论：这项研究为血友病患者的身体成分参数提供了宝贵的参考数据。与中度或轻度血友病患者相比，重度血友病患者的瘦体重明显偏低。不同严重程度表型之间的体脂率和脂肪增值率没有差异，但随着年龄的增长而增加。

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引用次数: 0

Differences and similarities in patient-reported outcomes among men and women with haemophilia 男女血友病患者在患者报告结果方面的异同。

IF 3 2区医学 Q2 HEMATOLOGY

Haemophilia

Pub Date : 2024-08-27 DOI: 10.1111/hae.15090

Christine L. Kempton, Sara A. Guasch, Tyler W. Buckner, Shanna Mattis, Stacey A. Fedewa

Introduction

Both men and women can be diagnosed with haemophilia and the experience with haemophilia may be different between men and women.

Aim

This study aimed to compare patient-reported outcomes in men versus women with haemophilia.

Methods

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.

Results

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.

Conclusions

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.

简介：男性和女性都有可能被诊断出患有血友病，而男性和女性的血友病经历可能有所不同：这项横断面研究是对血友病相关压力问卷验证研究中收集的数据进行的事后分析。2017年7月至2019年12月期间，从两个血友病治疗中心之一招募了年龄≥18岁的血友病A型或B型患者。研究结果包括生活质量、心理和生理健康指标以及总体健康状况。采用未调整和多变量线性回归模型来研究结果中性别差异的潜在中介因素：在 139 名研究参与者（21 名女性，118 名男性）中，平均年龄为 36.9 岁，大多数（89.2%）患有 A 型血友病。在未经调整和调整后的分析中，女性的 PHQ-9 抑郁症评分和 PROMIS-29 抑郁症和疲劳评分明显高于男性。其他结果在统计学上没有明显差异：结论：女性血友病患者比男性血友病患者更容易出现抑郁、焦虑和疲劳。这项研究强调了将心理健康服务纳入女性血友病患者护理的必要性。未来的研究需要了解女性血友病患者是否比非血友病患者更容易或更不容易患抑郁症、焦虑症和疲劳症，并确定心理健康下降对临床结果的影响。

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引用次数: 0

Comprehensive laboratory assessment of lonoctocog alfa versus octocog alfa in severe haemophilia A 对重症血友病 A 进行长效血友病α与八肽血友病α的综合实验室评估。

IF 3 2区医学 Q2 HEMATOLOGY

Haemophilia

Pub Date : 2024-08-20 DOI: 10.1111/hae.15089

Jens Müller, Thilo Albert, Claudia Klein, Silvia Horneff, Heiko Rühl, Bernd Pötzsch, Georg Goldmann, Natascha Marquardt, Johannes Oldenburg

Introduction

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.

Aim

To characterize lonoctocog alfa versus octocog alfa in pre- and post-infusion samples obtained from patients undergoing repeated investigation of incremental recovery (IR).

Methods

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.

Results

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.

Conclusion

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.

简介Lonoctocog alfa 是一种单链因子 VIII (FVIII) 分子，与 von-Willebrand 因子的结合亲和力很高。众所周知，单阶段凝血测定法（OSCA）低估了其血浆活性，但人们对长链苜蓿在全凝血测定法中的输注后表现或其对体内止血平衡的潜在影响还缺乏了解。目的：对接受增量恢复（IR）反复调查的患者输注前和输注后样本中的长链苜蓿与八链苜蓿进行比较：共纳入18名重症血友病A患者（lonoctocog alfa：10人，octocog alfa：8人）。采用了一组特异性因子和整体凝血测定，包括 FVIII OSCA、两种 FVIII 色原底物测定（CSA）、旋转凝血活酶图和凝血酶生成（TG）。通过测量血浆凝血酶标记物和活化蛋白 C 的水平来评估潜在的凝血活化：结果：发现lonoctocog alfa和octocog alfa的IR值相当（分别为2.36 [IU/dL]/[IU/kg]对2.55 [IU/dL]/[IU/kg]）。FVIII OSCA低估了lonoctocog alfa的活性，而两种FVIII CSA对lonoctocog alfa的检测差异也具有统计学意义。两种 FVIII 产品对旋转凝血活酶图的影响不如对 TG 参数的影响明显。未发现输注前血浆凝血生物标志物水平升高或输注后血浆凝血生物标志物水平发生明显变化：结论：lonoctocog alfa 和 octocog alfa 在体内显示出相似的恢复性和安全性，在体外对 TG 的影响也相似。观察到的 lonoctocog alfa 检测差异表明，不同 FVIII CSAs 的检测结果也存在差异。

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引用次数: 0

Driving improvement of diagnosis and awareness of heavy menstrual bleeding in women among physicians 提高医生对妇女大量月经出血的诊断和认识。

IF 3 2区医学 Q2 HEMATOLOGY

Haemophilia

Pub Date : 2024-08-20 DOI: 10.1111/hae.15088

Rezan Adbul Kadir, Ahmad Tarawah, Naveen Shridhar, Roshni Kulkarni

Introduction

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.

Aim

To evaluate awareness and perception of heavy menstrual bleeding (HMB) and bleeding disorders among HCPs and women/girls.

Methods

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.

Results

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.

Conclusion

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.

导言：患有出血性疾病的妇女/女童在护理方面存在许多障碍。目的：评估医护人员和妇女/女童对大量月经出血（HMB）和出血性疾病的认识和看法：方法：我们开展了一项分为三个部分的定性研究，包括来自七个以上国家的卫生保健人员和妇女/女童。第 1 部分包括 11 次 60 分钟的专家访谈，讨论 HMB 诊断障碍，第 2 部分对 6099 名妇女/女童、353 名全科医生（GP）和 426 名妇产科医生（OB/GYN）进行调查，进一步评估这些障碍。第三部分包括三个 1.5-2 小时的研讨会，20 名临床医生和患者代表参加了研讨会，内容涉及人乳头瘤病毒知识、人乳头瘤病毒的定义标准和医生诊断资源：结果：许多保健医生没有对出现 HMB 的妇女/女孩进行某些检查，22% 的全科医生对 HMB 的管理缺乏信心。只有 8%的全科医生使用筛查工具来评估月经失血，13%的全科医生和 15%的妇产科医生评估潜在的出血性疾病。76%的月经期妇女/女孩认为她们能够 "很好地 "识别 HMB 症状。然而，其中 23% 的妇女/女孩不会因月经异常/经期延长扰乱其生活而寻求医疗建议。据报告，34%的普通妇女/女童和 61% 的有 HMB 高危症状的妇女/女童的生活受到了干扰：结论：许多妇女/女童和医护人员对重要的 HMB 指标认识有限。有必要制定标准化的临床标准，以提高诊断和管理的效率。

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引用次数: 0

Transitioning patients with severe haemophilia A from emicizumab prophylaxis to valoctocogene roxaparvovec gene therapy: Real-world clinical experience 将重症血友病 A 患者从 emicizumab 预防治疗过渡到 valoctocogene roxaparvovec 基因治疗：真实世界的临床经验。

IF 3 2区医学 Q2 HEMATOLOGY

Haemophilia

Pub Date : 2024-08-13 DOI: 10.1111/hae.15086

Robert Klamroth, Saskia Gottstein

<p>Dear Editor</p><p>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.<span><sup>1, 2</sup></span> It uses an adeno-associated virus serotype 5 to deliver a functional copy of the B-domain-deleted factor VIII (FVIII)-encoding gene, <i>F8</i>, to hepatocytes, via a single infusion, to allow long-term expression of endogenous FVIII and prevention of bleeding in adults with severe haemophilia A.<span><sup>3</sup></span></p><p>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.<span><sup>4-6</sup></span> 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.<span><sup>4</sup></span> It acts by mimicking the function of activated FVIII and has a half-life of approximately 28−34 days.<span><sup>7</sup></span></p><p>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 <i>Haemophilia</i>, is how to transition patients from one therapy to another.<span><sup>8</sup></span> 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.</p><p>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 < 5 IU/dL at Week 4, prescribers should consider continuing emicizumab prophylaxis until two consecutive weekly measurements of ≥ 5 IU/dL are achieved.</p><p>Here, we present details of our real-world clinical experience of transitioning an adult male patient with severe haemophilia

亲爱的编辑Valoctocogene roxaparvovec 是一种基因疗法，已于 2022 年在欧洲、2023 年在美国获准用于治疗成人重症 A 型血友病患者、2 它使用 5 号血清型腺相关病毒，通过单次输注向肝细胞递送 B-域缺失的因子 VIII（FVIII）编码基因 F8 的功能拷贝，以实现内源性 FVIII 的长期表达并预防严重血友病 A 型成人患者的出血。Emicizumab 是一种人源化、重组、双特异性单克隆抗体，自 2018 年起在美国和欧洲获批作为重症 A 型血友病患者的常规预防用药，无论 FVIII 抑制剂状态如何。Emicizumab 的皮下注射剂量为 3 毫克/千克，头 4 周每周一次，随后维持剂量为 1.5 毫克/千克，每周一次，3 毫克/千克，每 2 周一次或 6 毫克/千克，每 4 周一次。7 虽然重症甲型血友病基因疗法的问世是一个重要的治疗里程碑，但新疗法可能会给医生带来挑战，即如何在患者当前的治疗方案中实际应用新疗法。8 Agarwal 等人利用药代动力学模拟，确定了患者从依米珠单抗预防治疗过渡到 valoctocogene roxaparvovec 基因治疗时维持止血控制的最佳方法。在两种过渡方案中，对三种已获批准的埃米珠单抗给药方案（每周一次、每 2 周一次和每 4 周一次）的出血风险进行了估算：在valoctocogene roxaparvovec 输注当天给予最后一次埃米珠单抗给药与输注后 4 周给予最后一次埃米珠单抗给药。无论采用哪种埃米珠单抗给药方案或情况，止血控制都能得到维持，这表明在临床中，有几种方法可以让患者从埃米珠单抗预防治疗安全过渡到valoctocogene roxaparvovec基因治疗。作者建议，应在输注valoctocogene roxaparvovec 后 4 周评估 FVIII 活性水平。如果第 4 周时 FVIII≥5 IU/dL，且第 5 周时仍≥5 IU/dL，则可考虑停用埃米珠单抗。如果第 4 周时 FVIII 活性为 5 IU/dL，处方医生应考虑继续使用依米珠单抗进行预防，直到连续两周每周测量值≥ 5 IU/dL。在此，我们详细介绍了一位成年男性重症血友病 A 患者在没有洗脱期的情况下从埃米珠单抗预防性治疗过渡到 valoctocogene roxaparvovec 基因治疗的实际临床经验。在改用埃米珠单抗后，患者的出血事件频率有所下降；在使用埃米珠单抗的整个期间，他的左肘发生过一次自发性出血，左手腕怀疑发生过几次出血和微出血。2023 年，valoctocogene roxaparvovec 在德国获准用于成人重症 A 型血友病患者9 后，患者开始对转用基因疗法感兴趣，希望能更可靠地预防肘部出血。虽然他没有 "大量出血 "的表型，但他一直害怕出血，密切关注各种症状和体征，肘部出血也让他很担心。他还表示希望摆脱反复注射和终身预防性注射的负担。在仔细考虑了益处和风险（短期和长期）之后，包括如果他出现转氨酶炎，可能需要接受一个反应性皮质类固醇疗程来保护 FVIII 的表达，患者和临床团队共同决定改用基因疗法。在患者输注 valoctocogene roxaparvovec 之前，埃米珠单抗的给药频率没有改变。2023 年 6 月，他血液中的埃米珠单抗浓度为 77 µg/mL。因此，在进行基因治疗时，假定其稳态浓度为 77 微克/毫升。2023 年 11 月输注valoctocogene roxaparvovec 前 3 天，患者停用了埃米珠单抗。采取这种方法的依据是，埃米珠单抗的消除半衰期约为 28 天，停止治疗后，其在体内的保护水平为 30 微克/毫升，至少可维持 4 周。

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引用次数: 0

Factor V haemostatic diathesis impairing thrombin activation, membrane binding and circulating antigen level due to a novel compound heterozygous mutation, Leu1821Ser and Gly2192Cys 因 Leu1821Ser 和 Gly2192Cys 的新型复合杂合突变而导致凝血因子 V 型止血障碍，影响凝血酶活化、膜结合和循环抗原水平。

IF 3 2区医学 Q2 HEMATOLOGY

Haemophilia

Pub Date : 2024-08-08 DOI: 10.1111/hae.15087

Kimberley Talbot, Jina Song, John R. Perrier, Shannon Jackson, Ross T. A. MacGillivray, Edward L. G. Pryzdial

Introduction

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.

Aim

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.

Methods and Results

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 <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 (r) FV/L1821S was impaired, and rFV/G2192C was unable to bind to a procoagulant phospholipid membrane.

Conclusion

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.

导言：先天性第五因子（FV）缺乏症是一种罕见的凝血功能障碍，发病率为1/100,000,000，出血严重程度差异很大，其原因尚不清楚。目的：为了帮助理解FV缺乏症患者所观察到的表型的分子基础，我们对导致患者FV缺乏症的遗传学和生物化学进行了评估：一位 71 岁的女性患者，因长期严重出血而导致子宫切除术，她的血浆 FV 抗原只有正常值的 3%，且电泳迁移率正常。血小板 FV 含量同样很低，但其条带形态不如正常人那么破碎。血浆凝血活性为结论：这些发现与观察到的表型一致，强调了了解 FV 生化功能的重要性，以便在循环抗原水平不一致时合理判断临床出血严重程度。

{"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, Jina Song, John R. Perrier, Shannon Jackson, Ross T. A. MacGillivray, 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 <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}

引用次数: 0

Bioclinical features of haemophilia patients in Benin in 2023: Towards better care 2023 年贝宁血友病患者的生物临床特征：实现更好的护理。

IF 3 2区医学 Q2 HEMATOLOGY

Haemophilia

Pub Date : 2024-08-08 DOI: 10.1111/hae.15082

Tatiana Baglo, Alban Zohoun, Falilatou Agbeille Mohamed, Ferrelle Araba, Bienvenu Houssou, Ludovic Anani, Dorothée Kindé-Gazard, Awa Touré Fall, Anne Ryman, Yves Gruel, Claire Pouplard

Objective

To analyse the demographic, clinical and laboratory data of Beninese patients with haemophilia.

Method

A prospective survey was conducted in three different hospitals of Benin from April 2021 to March 2022, to analyse clinical and biological features of patients with haemophilia previously diagnosed or identified based on personal/family history.

Results

A total of 101 patients were studied, 97 with haemophilia A and 4 with haemophilia B, including 26 new cases identified after family investigation. Their median age was 11 years, and the most frequent initial manifestations were cutaneous-mucosal haemorrhages (29.70%) and post-circumcision haemorrhages (25.74%). Previous joint bleedings were present in 77% of them, with an arthropathy in 65 cases, which particularly affected the knees (75%), elbows (41%) and ankles (29%). Factor VIII (FVIII) levels combined with activated partial thromboplastin time (APTT) values did not always enable, as would be expected, the distinction between severe and moderate haemophilia, since they were >1 IU/dl in 31 of 74 patients with APTT > 80 s, and between 1 and 2 IU/dl in 26 other cases with previous joint haemorrhages, including 18 with chronic arthropathy. Therefore, for these patients, severe haemophilia could not be excluded, and this uncertainty probably reflects technical difficulties affecting the pre-analytical and analytical stages of the APTT and FVIII/IX assays.

Conclusion

Our study proved that haemophilia is a significant reality in Benin, but also remains under-diagnosed in some districts of the country. In addition, more reliable biological tests are needed in the future to better define the severity of the disease and improve treatment of patients.

目的：分析贝宁血友病患者的人口统计学、临床和实验室数据：分析贝宁血友病患者的人口、临床和实验室数据：2021年4月至2022年3月，在贝宁三家不同的医院进行了一项前瞻性调查，分析先前诊断出的或根据个人/家族病史确定的血友病患者的临床和生物学特征：共有 101 名患者接受了研究，其中 97 人为 A 型血友病患者，4 人为 B 型血友病患者，包括 26 名通过家庭调查发现的新病例。他们的中位年龄为 11 岁，最常见的初期表现是皮肤黏膜出血（29.70%）和包皮环切后出血（25.74%）。77%的患者曾有过关节出血，65例出现关节病变，尤其是膝关节（75%）、肘关节（41%）和踝关节（29%）。因子 VIII（FVIII）水平与活化部分凝血活酶时间（APTT）值相结合，并不总能像预期的那样区分重度和中度血友病，因为在 74 例 APTT > 80 秒的患者中，有 31 例的因子 VIII（FVIII）水平大于 1 IU/dl，另有 26 例患者的因子 VIII（FVIII）水平介于 1 至 2 IU/dl之间，其中包括 18 例慢性关节病患者。因此，不能排除这些患者患有严重的血友病，这种不确定性可能反映了影响 APTT 和 FVIII/IX 检测的分析前和分析阶段的技术困难：我们的研究证明，血友病在贝宁是一个重要的现实问题，但在该国的一些地区仍然诊断不足。此外，未来还需要更可靠的生物检测，以更好地确定疾病的严重程度，改善对患者的治疗。

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引用次数: 0

Sexual functioning in men with haemophilia: Data from the haemophilia in the Netherlands-6 study 血友病男性患者的性功能：来自荷兰血友病 6 研究的数据。

IF 3 2区医学 Q2 HEMATOLOGY

Haemophilia

Pub Date : 2024-08-07 DOI: 10.1111/hae.15083

Tessa C. M. van Gastel, Lorynn Teela, Evelien P. Mauser-Bunschoten, Michiel Coppens, Marjolein Peters, Karin C. J. Fijnvandraat, Lotte Haverman, Samantha C. Gouw

引用次数: 0

Acute neuromuscular and perceptual responses to blood flow restriction exercise in adults with severe haemophilia: A pilot study 严重血友病成人患者对血流限制运动的急性神经肌肉和知觉反应：试点研究。

IF 3 2区医学 Q2 HEMATOLOGY

Haemophilia

Pub Date : 2024-08-04 DOI: 10.1111/hae.15084

Daniel C. Ogrezeanu, Joaquín Calatayud, Sergi Rodríguez, Juan J. Carrasco, Eduardo Martinez-Valdes, José Casaña, Carlos Cruz-Montecinos, Lars L. Andersen, Per Aagaard, Rubén López-Bueno, Sofía Pérez-Alenda

Introduction

No previous studies have implemented a standard blood flow restriction (BFR) training session in people with severe haemophilia (PwH), where this type of training has been contraindicated.

Aims

The purpose of this study was to evaluate the tolerability, adverse events, and neuromuscular and perceptual responses to an acute session of low load (LL) knee extensions with BFR in PwH under prophylaxis.

Methods

Eight PwH performed one LL-BFR session with 40% arterial occlusion pressure (AOP). Perceptual responses and adverse effects were assessed, together with high-density surface electromyography of vastus medialis (VM) and lateralis (VL).

Results

Significant normalized root mean square differences were found within each set, but not between sets. Spatial distribution (centroid displacement (p > .05), modified entropy (VM, set two, cycles three and five, p = .032) and coefficient of variation (VM, set two, cycles four and five lower than cycle three (p = .049; p = .036)) showed changes within each set. Median frequency showed a slight increase during cycle four of set four (p = .030). Rate of perceived exertion slightly increased with each set while tolerability slightly decreased in the last set and fear of training with BFR generally decreased after the session.

Conclusions

In PwH, a LL-BFR session at 40% AOP is safe and feasible. Our results suggest that potential muscle impairments may blunt neuromuscular adaptations induced by BFR.

导言：目的：本研究旨在评估接受预防性治疗的重度血友病患者在急性低负荷（LL）膝关节伸展和血流限制（BFR）训练时的耐受性、不良反应以及神经肌肉和知觉反应：方法：8 名残疾人在 40% 的动脉闭塞压 (AOP) 下进行了一次低负荷膝关节伸展训练。方法：8 名 PwH 在 40% 的动脉闭塞压力（AOP）下进行了一次 LL-BFR 训练，并对感知反应和不良反应以及内、外侧肌的高密度表面肌电图进行了评估：结果：在每组中发现了显著的归一化均方根差异，但在组间没有发现。空间分布（中心点位移（p > .05））、修正熵（VM，第二组，周期三和五，p = .032）和变异系数（VM，第二组，周期四和五低于周期三（p = .049；p = .036））显示出每组内的变化。频率中位数在第四组第四周期略有增加（p = .030）。每组训练的感觉消耗率略有增加，而最后一组训练的耐受性略有下降，训练后对使用 BFR 进行训练的恐惧感普遍下降：对于残疾人来说，在 40% AOP 下进行 LL-BFR 训练是安全可行的。我们的研究结果表明，潜在的肌肉损伤可能会减弱 BFR 诱导的神经肌肉适应性。

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引用次数: 0