Haemophilia最新文献

Background: Haemophilic arthropathy (HA) is a frequent complication of haemophilia, where ferroptosis in chondrocytes significantly contributes to disease progression. Cold-inducible RNA-binding protein (CIRBP) is known to modulate disorders associated with ferroptosis; however, its specific effect on chondrocyte ferroptosis remains unclear. This research sought to explore the effects of CIRBP on ferroptosis in chondrocytes and to elucidate the underlying mechanisms.

Methods: Chondrocytes were treated with FAC to simulate an in vitro iron overload environment. Various methods, including cell viability assays, Western blotting, flow cytometry and immunofluorescence, were employed to assess the effects of CIRBP on chondrocyte cytotoxicity, ferroptosis-related proteins and oxidative stress.

Results: The results indicated that chondrocyte proliferation decreased in the iron overload environment, with increased levels of ferroptosis-related proteins GPX4 and SLC7A11, as well as reactive oxygen species (ROS), confirming the occurrence of ferroptosis in chondrocytes. Notably, CIRBP exacerbated this process. Ultimately, the inhibition of the CIRBP-mediated TLR4 pathway successfully alleviated chondrocyte ferroptosis.

Conclusion: This study provides deeper insights into the cell death pathways involved in HA and suggests that inhibiting the pro-ferroptotic effects of CIRBP may represent a potential therapeutic strategy for HA. Further research is needed to evaluate the chronic effects of this intervention in vivo.

Summary: Identifies a new pathological role for CIRBP: We found that cold-inducible RNA-binding protein (CIRBP) is elevated in the cartilage of Haemophilic Arthropathy (HA) patients and exacerbates iron-overload induced chondrocyte death. Links CIRBP to ferroptosis: For the first time, we demonstrate that CIRBP aggravates chondrocyte ferroptosis-a specific type of iron-dependent cell death-by increasing reactive oxygen species (ROS) and depleting key anti-ferroptosis proteins (GPX4 and SLC7A11). Proposes a novel therapeutic target: Inhibiting the TLR4 pathway with TAK-242 successfully alleviated CIRBP-driven ferroptosis, suggesting that targeting the CIRBP/TLR4 axis could be a viable strategy to protect cartilage in HA.

In recent decades the advances in care and therapeutic options for people with haemophilia have been extraordinary, transforming the lives of those with severe disease and access to treatment. In contrast, the treatments for those living with von Willebrand Disease (VWD) were largely developed over 20 years ago, with the first recombinant VWF product only recently achieving a licence for use in prophylaxis. Marking the 100th anniversary of the first reported case of a person with VWD, PwVWD and their healthcare providers need to continue to demand and work toward improved access to both diagnostics and better treatment internationally for PwVWD. Herein we reflect on the evolution of knowledge and care for PwVWD and review the current approaches to diagnosis. The limited current therapeutic options for prophylaxis and burden of infusions remain a hindrance to broad use in PwVWD who would benefit. There is, however, a changing landscape for PwVWD as, for the first time in VWD, multiple novel therapeutic approaches are either in or approaching clinical trial development. With these advances in mind, we look forward with hope toward rapid and sustained improvements in the next century for all PwVWD.

Introduction: Efanesoctocog alfa is a novel, "ultra-extended half-life" FVIII concentrate for bleed treatment and prevention in haemophilia A. Clinical trials excluded individuals with active or prior FVIII inhibitors, those on emicizumab, and previously untreated patients (PUPs).

Aim: This retrospective, single-centre study evaluated the management and outcomes of pediatric clinic patients who initiated efanesoctocog alfa for haemophilia A bleed treatment or prevention.

Methods: Clinical characteristics, pharmacokinetic data, hemostatic outcomes, and non-standardised patient and caregiver feedback were collected by medical record review.

Results: Overall, 24 patients initiated efanesoctocog alfa, including seven who switched from emicizumab, five who previously achieved immune tolerance induction for FVIII inhibitors, and one PUP, who was successfully treated with a single infusion for his initial joint bleed. Mean FVIII activity on day 6 was 13.4 ± 6.1 IU/dL by one-stage assay for patients who switched from FVIII concentrate prophylaxis. Five switched from emicizumab without a washout, preventing the use of a one-stage assay, and had a mean chromogenic FVIII activity of 23.8 ± 5.2 IU/dL on day 6. Compared with prior prophylaxis, efanesoctocog alfa was associated with a lower mean treated annualised bleed rate (1.3 ± 1.5 vs 0.1 ± 0.3, p = 0.001) and annualised emergency department bleed evaluations (0.8 ± 1.4 vs 0.1 ± 0.4, p = 0.04). No recurrence of FVIII inhibitors occurred over a median follow-up of 22.6 months (range: 6.4-25.4). Patients/caregivers reported improvements in musculoskeletal discomfort, perception of hemostatic coverage, and confidence to pursue physical activity.

Conclusion: Individuals with clinically severe haemophilia A, including subgroups previously excluded from clinical trials, successfully transitioned to efanesoctocog alfa with excellent hemostatic outcomes and no inhibitor recurrence.

Background: Glanzmann thrombasthenia (GT) is an inherited platelet disorder resulting in severely reduced platelet aggregation and increased bleeding tendency. Pregnancy and childbirth in women with GT present significant challenges for both mother and child.

Objective: The aim of this study was to present the current clinical practices in pregnancy and childbirth in GT.

Methods: A survey on the management of the preconception phase, pregnancy and childbirth in women with GT was conducted by the European Association of Haemophilia and Allied Disorders.

Results: Thirty-seven responses from 18 countries were analysed. Almost all respondents recommended multidisciplinary preconception counselling, though 11% lack access to obstetrics and gynaecology services focused on bleeding disorders. Delay in conceiving was reported by 62%. Ninety-one percent of respondents indicated that they would screen for platelet alloimmunisation; however, the timing of screening varied. The recommended treatment to prevent postpartum haemorrhage (PPH) most often comprised tranexamic acid (TXA) and recombinant activated factor VII (rFVIIa) (25%) or TXA, rFVIIa and platelet transfusion (22%). The latter combination was also the most frequently recommended treatment to have on standby. Seventy-five percent would advise a mode of delivery as per obstetric indication and 69% would recommend to avoid neuraxial anaesthesia. Half of the respondents would add pharmacological thromboprophylaxis.

Conclusion: There is general consensus on the importance of preconception counselling, the screening for platelet alloimmunisation and the preferred mode of delivery. Opinions regarding the treatment of PPH and the use of thromboprophylaxis vary. The next step is to improve guideline implementation in daily practice while working toward an international consensus-based guideline.

Introduction: Coagulation testing in haemophilia A is limited by the scarcity of testing facilities capable of performing relevant assays. This issue incentivized the development of the EnzySystem for haemophilia A, a near-patient testing platform aimed to measure Factor VIII activity and thrombin generation simultaneously within 1 h from 100 µL of whole blood. Involving end-users throughout the development ensures innovations are well-suited to meet real-world clinical needs.

Aim: To determine EnzySystem's acceptance, envisioned use scenarios and determinants for implementation according to healthcare providers (HCPs) and persons with haemophilia A and caregivers (PwHA/C).

Methods: A single-centre, cross-sectional mixed methods study was performed involving two participant groups. The first involved 36 PwHA/C. The second group comprised five advanced practice providers, eight nurses, four pharmacists and five haematologists, all involved in haemophilia A care. The participants' attitudes and preferences toward the EnzySystem for haemophilia A were assessed through questionnaires and focus groups.

Results: Acceptability was high for both groups. The platform was considered suitable for use in various scenarios, but self-testing at home was prioritized by PwHA/C. HCPs placed equal emphasis on near-patient testing in clinic to address issues with current test accessibility and turnaround time. For all potential use scenarios, demonstrating assay accuracy was a non-negotiable prerequisite. The turnaround time and accessibility were identified as other key attributes by both groups.

Conclusion: The results of this study support the further development of the EnzySystem for haemophilia A and highlight barriers that should be addressed to facilitate implementation.

Introduction: Haemophilia A in paediatric patients presents a lifelong risk of spontaneous and trauma-induced haemorrhage, leading to progressive joint damage, disability and impaired quality of life. Emicizumab, a bispecific monoclonal antibody administered subcutaneously, offers sustained haemostatic protection and has shown promising outcomes in children.

Aim: To systematically evaluate and quantitatively synthesise the efficacy, safety and immunogenicity outcomes of emicizumab prophylaxis in paediatric patients with haemophilia A.

Methods: This systematic review and meta-analysis was conducted according to PRISMA 2020 guidelines and registered in PROSPERO (CRD420251145633). Eligible studies reported quantitative outcomes for children with haemophilia A receiving emicizumab. Random-effects models were used to pool median annualised bleeding rates (ABR) and prevalence of joint bleeding, intracranial haemorrhage (ICH), inhibitor development and anti-drug antibodies (ADA).

Results: Eighteen studies comprising 720 paediatric patients were included. The pooled median ABR was 0.50 bleeds/year (95% CI: 0.00-1.11), and no cases of ICH were reported across all studies. The pooled prevalence of joint bleeds was 5.4% (95% CI: 1.41-10.96), reflecting effective musculoskeletal protection. Inhibitor development occurred in less than 0.01% of patients (nine cases), and ADA were reported in five cases without loss of clinical efficacy. No significant differences were observed in subgroup analyses by study design or geographic region.

Conclusions: Emicizumab prophylaxis provides robust and consistent bleed prevention with an excellent safety and immunogenicity profile in children with haemophilia A. The near-zero ABR and absence of intracranial haemorrhage highlight its potential to transform long-term outcomes and prevent haemophilic arthropathy.

Introduction: Haemophilic elbow arthropathy (HEA) causes pain, limits mobility, and impairs upper limb function, often unrecognised until irreversible damage has occurred.

Aims: This narrative review sought to provide an updated overview of the current state of HEA knowledge, treatment approaches, and future perspectives.

Methods: We searched the PubMed/Medline, Embase and Scopus (through April 2025) databases for English articles using a combination of controlled vocabulary and free-text keywords related to haemophilia, elbow arthropathy, range of motion, physiotherapy, surgical interventions, and joint assessment. The review was organised around six key themes: normal function of the elbow, progressive loss of its mobility and functionality, monitoring, role of physiotherapy and exercise, invasive solutions, and future perspectives. A total of 60 articles were retrieved, 45 of which were examined in depth.

Results: HEA significantly affects the quality of life of people with haemophilia (PwH). Its insidious onset, coupled with the body's ability to compensate, frequently obscures the severity of mobility loss, leading to delayed interventions and irreversible joint damage. Early detection, precise monitoring, and targeted physiotherapy are crucial to slowing down disease progression and optimising functional outcomes. Surgical interventions are considered only in advanced-stage HEA, and are typically reserved for cases where conservative treatments have proven insufficient. Technological and telemedicine advances provide novel avenues to optimise care and promote patient self-management.

Conclusions: HEA is a progressive, often overlooked condition that reduces quality of life in PwH, highlighting the need for early detection, monitoring, and targeted physiotherapy to prevent irreversible joint damage.

Nagao A, Chikasawa Y, Sawada A, et al. Haemophilia and cardiovascular disease in Japan: Lowincidence rates from ADVANCE Japan baseline data.Haemophilia. 2023;29:1519–1528. https://doi.org/10.1111/hae.14876

In the above article, errors were identified in several numerical values presented in the published tables and figure, due to inaccuracies in the initial data collection process. The corrected versions of Table 1, Table 2, Table 5, and Figure 1 are provided below.

Please note that some numerical values cited in the main text may also differ from those originally published. However, these corrections do not alter the overall interpretation or conclusions of the study.

We apologize for this error.

V. Myroslav, S. Nataliya, S. Oleksandra, K. Valeriia, and H. Sofiia, “Abstract: The Investigation of Frequency of Prothrombin (FII) and Factor Leiden (FV) Mutations In Patients With Haemophilia,” Volume 31, 13th BIC International Conference, 12–14 September 2025, https://doi.org/10.1111/hae.70107

Myroslav Voroniak, Nataliya Shurko, Oleksandra Stasyshyn, Valeriia Krasivska, Sofiia Hudzij

State Institution “The Institute of Blood Pathology and Transfusion Medicine NAMS of Ukraine”, Lviv, Ukraine

In the above article, the authors' list was incomplete. The correct authors list is Myroslav Voroniak, Nataliya Shurko, Oleksandra Stasyshyn, Valeriia Krasivska, Sofiia Hudzij.

We apologize for this error.