Haemophilia最新文献

Introduction

The pandemic affected the quality of life (QoL) of children with haemophilia, nevertheless their caregivers. The disease burden to caregivers and its influence on well-being may become a determinant of the quality of care they provide, impacting the overall patient's outcome.

Aims

This study aimed to determine the effects of the pandemic on the caregiver burden, QoL, anxiety and/or depressive symptoms of caregivers.

Methods

Validated questionnaires: Modified Caregiver Strain Index Pilipino (MCSI-P), Hospital Anxiety and Depression Scale (Pilipino) (HADS-P) and WHO-5 Well Being Index (Pilipino) were given to caregivers of paediatric haemophilia patients in the patient roster.

Results

Among the 72 participants, 21 had caregiver strain/burden, while five had impaired QoL pre-pandemic. During the pandemic, the prevalence of caregiver strain (55.6%) and impairment in QoL (20.8%) significantly increased. While the pre-pandemic prevalence of caregiver burden was comparable from data in published literature, there was a significant increase during the pandemic. Anxiety (8.3%) and depressive symptoms (4.2%) among caregivers were below the pre-pandemic range and did not significantly increase during the pandemic. Impaired QoL was not associated with depressive/anxiety symptoms, but it was observed that caregivers showed more anxiety than depressive manifestations.

Conclusion

The pandemic significantly increased the prevalence for caregiver burden. Increased rates of psychological symptoms were observed during the pandemic, but not statistically significant. There was no association between impaired QoL and caregivers’ psychological symptoms. While much focus was given to the patients themselves, paramount attention to caregiver burden and compromised QoL should be evaluated and addressed as well.

This is a plain language summary on switching from the medicine octocog alfa to a new medicine damoctocog alfa pegol (BAY 94–9027, Jivi) for the treatment of haemophilia A in Canada.

Introduction

Although clinical experience of a triple-secured, plasma-derived, von Willebrand factor (pdVWF), almost devoid of Factor VIII (FVIII) in adults with von Willebrand disease (VWD), is widely reported, its use in children is less documented.

Aim

To explore the safety and efficacy of this concentrate in real-life, in children <12 years old.

Methods

Data from 30 paediatric patients enrolled in a prospective, 3-year observational, post-marketing study in France were analysed. Efficacy and safety were assessed in two cohorts: 0–6 and 6–11 years old.

Results

The population included 14 children <6 years of age and 16 children aged 6–11 years. Most patients (80%) were severely affected (von Willebrand factor ristocetin cofactor activity [VWF:RCo] ≤ 15 IU/dL), including 30% with Type 3 VWD. Children received pdVWF for 16 major bleeds, 138 minor bleeds, 7 major surgeries, 8 minor surgeries and 12 invasive procedures. Efficacy was rated excellent or good in 100% of major bleeds or surgeries. The dose per infusion was approximately 50 IU/kg. By age group, median doses per infusion varied from 49 to 73 IU/kg for patients <6 years and from 46 to 59 IU/kg for patients 6–11 years, according to clinical situation. FVIII coadministration/correction was more frequent in Type 3 VWD, regardless of patient's age. Of five children receiving long-term prophylaxis, breakthrough bleeding occurred in 1.6% of infusions and median annualised bleeding rate was 0.8. No safety concerns were raised.

Conclusion

This analysis enlarges clinical experience of an FVIII-poor pdVWF in the paediatric population. This concentrate offers safe and effective treatment regardless of VWD severity.

Introduction

Haemophilia is an X-linked bleeding disorder characterized by deficient or defective clotting factors. Obesity in persons with haemophilia (PwH) is associated with joint mobility issues, decreased range of motion and increased target joints. Complications of inhibitors, antibodies that neutralize clotting factor concentrate, can limit physical activity, potentially exacerbating obesity risk. This study examines the association between obesity and inhibitor status in PwH and explores the impact of emicizumab, a bispecific monoclonal antibody, on obesity trends.

Methods

A retrospective cohort analysis of the American Thrombosis and Hemostasis Network ATHNdataset from 2013 to 2021 was conducted. The study included 19,074 males with haemophilia A or B with at least one recorded body mass index measurement. Statistical analyses included logistic regression, generalized estimating equations and difference-in-difference models to assess obesity trends and associations with inhibitors and emicizumab use.

Results

Obesity prevalence significantly increased in paediatric and adult PwH (p < 0.001). Children had a significantly increased risk of inhibitors compared to adults with either haemophilia A or B. A history of target joints and emicizumab use was associated with an increased obesity risk. No significant difference in obesity prevalence was found in adult or paediatric PwH with or without exposure to emicizumab. No significant association was observed between obesity and inhibitor status.

Conclusion

Obesity prevalence in PwH continues to rise, aligning with trends in the general population. The link between target joints and obesity highlights the need to reduce obesity and improve joint health; future studies should explore causality and how physical activity mediates these associations.

Background

Neutralising antibodies (inhibitors) against factor VIII can result in severe bleeding in persons with nonsevere haemophilia A (NSHA). The INSIGHT study of 1112 persons with NSHA in a predominantly White population identified 19 different F8 missense variants that were associated with inhibitor development.

Objective

To describe the F8 variants and inhibitor development in persons with NSHA in a multiethnic cohort using the My Life, Our Future (MLOF) Research Repository and the American Thrombosis and Hemostasis Network dataset (ATHNdataset).

Methods

The MLOF Research Repository and ATHNdataset were queried for demographic, clinical and genotyping data.

Results

A total of 1805 persons with NSHA with at least one reportable F8 variant and known inhibitor status were included in this study. Inhibitors were developed in 142 (7.9%) persons with NSHA. Inhibitor development occurred in seventy F8 variants, of which the majority (n = 67, 95.7%) were missense variants. These 70 F8 variants were identified in a total of 1006 (55.7%) persons with NSHA. Race or ethnicity was not associated with inhibitors in persons with NSHA.

Conclusion

The MLOF Research Repository identified additional F8 variants where inhibitor development occurred in a multiethnic cohort of NSHA. Identification of these F8 variants can inform both physicians and persons with NSHA to adopt measures to reduce the risk of inhibitor development.

Introduction

Different strategies in prophylaxis for haemophilia among countries may affect long-term outcome.

Aim

The aim of this study is to compare joint health in persons with severe haemophilia (PwSH) between Sweden and Greece, based on different approaches on prophylaxis initiation and management.

Methods

Data were extracted from the PedNet Registry, which collects patient data prospectively, regarding measures on treatment and joint health using Haemophilia Joint Health Score (HJHS) and Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US).

Results

Sixty-one Swedish and 51 Greek PwSH (aged ≥ 10–18 years) were included. Swedish adolescents were diagnosed at earlier age (0.53 vs. 0.77 years in Greece, p < 0.01). At prophylaxis initiation {earlier in Sweden (p < 0.01)}, dose regimens were more intense and escalation to full prophylaxis was reached earlier in Sweden. Median age at the last HEAD-US was 15.82 versus 14.07 years and at the last HJHS: 15.26 versus 15.86 years, for Sweden and Greece, respectively. Swedish and Greek PwSH had similar median total HJHS: 1.5 versus 1.0, respectively, p = 0.38. Based on HEAD-US, signs of synovitis were less frequent in Sweden for ankles (31.1% vs. 72.2%; p < 0.01), knees (11.1% vs. 44.4%, p < 0.01) and elbows (8.9% vs. 27.8%, p < 0.05). Bone/cartilage abnormalities were also less frequent in Swedish patients (ankles: 11.1% vs. 30.6%; p < 0.05, knees: 6.7% vs. 11.1%; p = 0.69, elbows: 8.9% vs. 19.4%; p = 0.20).

Conclusion

Although adolescent PwSH clinically have good joint health in both countries, differences were detected by HEAD-US, with earlier prophylaxis in Sweden being associated with better joint outcomes.

Introduction

Haemophilia A and B are hereditary bleeding disorders that require multidisciplinary perioperative management. Data on orthopaedic surgery outcomes with extended-half-life (EHL) recombinant Fc-fusion factor VIII (rFVIIIFc) and factor IX (rFIXFc) products remain limited.

Aims

To evaluate the efficacy of EHL rFVIIIFc or rFIXFc in major orthopaedic surgery, focusing on haemostasis, safety and factor consumption.

Methods

This prospective study involved persons with haemophilia A or B treated with rFVIIIFc or rFIXFc undergoing orthopaedic surgery.

Results

Twenty major orthopaedic surgeries (2018–2023) were included in 19 persons with severe or moderate haemophilia A (n = 14) or B (n = 5), median age 46 years (range 26–60). Procedures included arthroplasty, arthrodesis, arthroscopic synovectomy, prosthetic revision of the knee or ankle, and removal of a femur fracture fixation device. Median hospital stay was 7 days (range 2–18). Median cumulative factor consumption was 300 and 388 IU/kg for haemophilia A and B, respectively. Haemostatic efficacy was rated as ‘good’ in 95% (n = 18) of cases, ‘poor’ in 5% (n = 1), and not documented in one case. Median haemoglobin (Hb) change was –2.0 g/dL (range –4.6 to +0.5); no transfusions were required. Complications were reported in 45% (n = 9) of cases (anaemia 40%; blood loss 5%) and managed with oral supplementation of iron and folates. No adverse events related to rFVIIIFc or rFIXFc administration were observed.

Conclusion

RFVIIIFc and rFIXFc provide effective haemostasis during orthopaedic surgery in patients with haemophilia A and B, with a favourable safety profile. Further multicentre studies are warranted to confirm these results and refine perioperative management guidelines.

Introduction

Despite the well-established lifelong impact of haemophilia on joint health, there remains a significant gap in our understanding of the developmental morphological changes that occur in the bones of haemophilic individuals. This study applied geometric morphometric measurement (GMM) to analyse age-related morphological variations in the knee joints of haemophilia patients.

Materials and Methods

This retrospective study analysed 210 anteroposterior knee radiographs from 15 male haemophilia patients (ages 8–24), grouped into 8–15, 16–20, and 21–24 years. Twenty 2D bony landmarks were annotated by two raters (ICC = 0.98). Generalized Procrustes analysis, principal component analysis, Procrustes ANOVA, and canonical variate analysis were performed. Associations with Pettersson score (PS) and Haemophilia Joint Health Score (HJHS) were examined via multivariate regression.

Results

The diversity in morphology of knee joints among the first five principal components was 83%. Procrustes ANOVA indicated significant shape differences (p < 0.001) among age groups. Furthermore, discriminant function analysis revealed the highest Mahalanobis distance (3.6212) between age group 1 and group 3, with significant differences (p < 0.001). Notable morphological alterations were identified, characterized by a medial displacement of the patella and a reduction in joint space.

Conclusion

This study revealed significant age-related morphological alterations in the knee joints of individuals with hemophilia. The position of the patella was identified as a key morphological marker, suggesting its potential utility for long-term follow-up and the development of targeted rehabilitation programs.