Haemophilia最新文献

Introduction: Haemophilia, an X-linked disorder, is linked to reduced bone mineral density (BMD). Emicizumab, a factor VIII (FVIII) mimetic, provides a model to study the role of FVIII in bone health.

Aim: To evaluate BMD in adults with severe haemophilia under different prophylactic regimens, focusing on whether emicizumab maintains bone health comparable to FVIII prophylaxis.

Methods: Forty male adults with severe haemophilia A or B were prospectively enrolled at a single centre (2019-2024) and assigned to five prophylactic groups: emicizumab (with/without inhibitors), FVIII, factor IX (FIX) or investigational agents. Annual assessments included dual-energy X-ray absorptiometry, joint status, mobility and bone turnover markers.

Results: Of the 40 patients, 18 received FVIII, 10 FIX, 4 haemophilia A with inhibitors on emicizumab, 4 haemophilia A without inhibitors on emicizumab and 4 investigational therapies. At baseline, spine BMD z-scores were comparable to age-matched norms, whereas hip BMD was significantly lower (median -0.8; p < 0.001). After 1 year, spine and hip BMD changes did not differ significantly across treatment groups (p = 0.9010 and p = 0.8073, respectively). Lower annual bleeding rate, middle age and BMI extremes were associated with BMD improvement. Emicizumab-treated patients, with or without inhibitors, showed non-inferior BMD outcomes compared to those receiving FVIII, with all 95% confidence intervals within the predefined margin (±0.5).

Conclusion: BMD outcomes did not differ across regimens. Emicizumab was comparable to FVIII, suggesting bleed control, not factor replacement, is key to bone health in haemophilia.

Plain language summary: People with haemophilia often have problems with joint bleeding, which can limit movement and reduce bone strength. Different treatments are now available to prevent bleeding, including factor replacement and newer medicines such as emicizumab. It is not clear whether these treatments affect bone health differently. In this study, we followed 40 adults with haemophilia and measured their bone health for 1 year. We found that bone outcomes were similar across all treatment groups. Emicizumab worked just as well as factor VIII in maintaining bone strength. This means that good bleeding control may be the key to keeping bones healthy in haemophilia, regardless of the treatment type.

Background: Bone diseases, such as low bone mineral density and osteoporosis is an emerging concern in people with haemophilia (PWH). As a consequence, PWH might experience fractures more frequently than the general population. Our primary aim was to compare the incidence of bone fractures in PWH and controls without bleeding disorders. The secondary aim was to identify factors associated with fractures in PWH.

Methods: This was a retrospective, matched cohort, study based on data from the Canadian Bleeding Disorders Registry and data from the Institute for Clinical Evaluative Sciences (ICES). PWH were eligible if alive on 1 January 2017. They were followed up to 31 March 2018. Age- and sex-matched controls were randomly selected with a 20:1 ratio. We analysed the data using multivariate regression models, adjusting for age, severity, inhibitor status, and comorbidities (Charlson Comorbidity index).

Results: 1080 PWH and 21,597 controls were included. 8.7% of PWH and 5.7% of controls experienced a fracture during the follow-up period. The adjusted hazard ratio (aHR) for a fracture was 1.46 [95% confidence interval (CI) 1.19; 1.80] in PWH. Severe haemophilia [adjusted odds ratio (aOR) 1.72, 95% CI 1.02; 2.93] and the presence or history of an inhibitor (aOR 2.42, 95% CI 1.08; 5.42) were risk factors for a fracture, after adjusting for age and comorbidities.

Conclusions: PWH have a higher risk of bone fractures than the general population. Amongst PWH, the severity of haemophilia and the presence or history of an inhibitor are risk factors for a bone fracture.

Introduction: Emicizumab has proven to be a turning point in the management of patients with Haemophilia A (HA). In resource-limited settings, data on low-dose emicizumab prophylaxis (LDEP) in HA patients are emerging.

Methods: Thirty-seven patients previously on factor FVIII prophylaxis or bypassing agents (BPAs) received LDEP at a dose of 3-mg/kg SC for 4 weeks, followed by 1.5-mg/kg SC every 2 weeks. The primary objective was to assess the efficacy of LDEP measured in the form of reduction in annualised bleed rates (ABR), treated joint bleed and conversion of target joint to non-target joint. The secondary objectives were to study the improvement in joint scores (HJHS and FISH score) and to assess quality of life.

Results: The median duration of LDEP was 15 months. On LDEP, the mean ABR was 0.41 ± 0.7 (median = 0; IQR: 0-0.6). Sixty-seven percent of patients had zero bleeds, and 66% of target joints converted to non-target joints. There was a significant improvement in HJHS, FISH and QoL in patients.

Conclusion: LDEP, although not optimal, remains an effective strategy in the prevention of bleeds, improvement of QOL and reduction of joint-related disability in HA patients in resource-constrained settings.

Background: People with haemophilia (PwH) are at increased risk of joint bleeding, often leading to haemophilic arthropathy. The Haemophilia Joint Health Score (HJHS) is widely used to evaluate joint health, but its interpretability is limited by the lack of age-based reference values.

Objective: This study aimed to develop national reference values for the HJHS in individuals with severe haemophilia using data from the Canadian Bleeding Disorder Registry (CBDR).

Methods: This cross-sectional study used CBDR data from 1 January 2018 to 31 December 2024. Participants aged ≥4 years with severe Haemophilia A or B and at least one HJHS score were included. Generalised Additive Models for Location, Scale, and Shape (GAMLSS) were used to estimate reference percentiles. Model performance was assessed using 100-fold cross-validation.

Results: A total of 551 participants with severe haemophilia were included, comprising 255 paediatric (<18 years of age) and 296 adult patients (mean age: 24 ± 17 years; range: 4-75; 87% with Haemophilia A). Reference percentiles (fifth to 95th) were generated for ages 4-70 years, demonstrating a positive association between age and HJHS scores. Cross-validation showed acceptable model consistency.

Conclusion: This study provides the first national age-based reference values for the HJHS in individuals with severe Haemophilia A and B. These values allow clinicians to interpret joint health scores relative to age-specific expectations. Future research should extend age-specific HJHS reference values to additional national registries to strengthen global interpretation and comparison of joint health outcomes.

Introduction: Despite therapeutic achievements in haemophilia care, there is still the need to monitor and define personal treatment outcomes and document results to achieve the best possible care. Hence, a need for unbiased, timely and comprehensive real-world information exists to support informed shared decision-making regarding treatment and care.

Aim: To describe a medical device for people living with haemophilia (PLWH) supporting an active involvement to achieve a near to normal life.

Methods: Florio HAEMO was developed as haemophilia monitoring platform to support PLWH and their care teams in documenting, interpreting and analysing personal reported outcomes. The tool was created partnering closely with PLWH and healthcare professionals to address previously unmet needs compared to existing applications.

Results: Florio HAEMO was launched in March 2020. Currently, it is available in 25 countries and 24 languages; 1558 PLWH (86% with haemophilia A) are registered users in 121 treatment centres across 20 countries. All users included are on a prophylactic treatment regimen.

Conclusion: Florio HAEMO allows the collection of contemporaneous data to monitor treatment, like factor level, adherence and consumption as well as monitoring treatment outcomes, including pain, bleeds, wellbeing and levels of physical activity to support self-management, shared decision-making and to enable better care for PLWH. Data collected over time may help to show the impact of individualised prophylaxis and may support the definition of factor levels required for good bleed and joint protection in a real world setting from daily life to physical activities.