Haemophilia最新文献

Introduction: Mortality and morbidity in persons with haemophilia (PWH) have decreased due to improved diagnosis and treatment along with comprehensive population outreach efforts, but the impact is not uniform in different countries.

Aim: The study aims to assess all-cause and intracranial haemorrhage (ICH)-specific mortality of PWH in India.

Methods: This is a retrospective, observational, multi-centric cohort study of 1020 haemophilia patients from three centres in India. The mortality data in the family was collected from personal interviews, and subsequently confirmed with the corresponding haemophilia treatment centres (HTCs). The demographic and clinical data, along with other comorbidities, were collected from the medical records.

Results: Among 170 reported deaths, 73 (42.9%) were caused by ICH, and 44 (25.9%) resulted from accidents or trauma. Gastrointestinal (GI) bleeding was the third most common cause of death, accounting for 27 cases (15.9%). The average and median ages at death were 27.7 and 26 years, respectively. None of the deceased cases were receiving any prophylactic or immune tolerance induction (ITI) therapy, and all had severe haemophilia. In addition, the prevalence of inhibitors and hypertension was significantly higher in deceased cases compared to that in the general haemophilia population (p < 0.05).

Conclusion: Severity of haemophilia, episodic treatment, hypertension and inhibitors showed significant association with mortality. ICH continues to be the leading cause of death among haemophilia patients in the country. This underscores the challenges in managing haemophilia and the need for improved treatment strategies to increase the life expectancy of PWH.

Introduction: Eptacog beta is a novel human recombinant FVIIa approved for use in the United States, European Union, United Kingdom and Mexico for the treatment and control of bleeding in patients with haemophilia A or B with inhibitors (≥12 years). It is also indicated for perioperative care in the same patient population in Europe and the United Kingdom.

Aim: To assess the incidence of rebleeding and review treatment outcomes in subjects with haemophilia with inhibitors enrolled in the phase 3 PERSEPT 1 clinical trial.

Methods: To treat mild/moderate bleeding episodes (BEs), subjects administered an initial 75  or 225µg/kg dose of eptacog beta, followed (if necessary) by additional 75µg/kg doses at predefined intervals until bleed control. This analysis used subject-reported rebleeding to determine a rebleeding incidence for the first 24 h. Rebleeding through later timepoints was an exploratory, intention-to-treat analysis of bleed treatment data.

Results: Four hundred and sixty-five BEs were analysed. Through 24 h, the proportion of rebleeds was 0% (initial 75µg/kg dose) and 0.5% (initial 225µg/kg dose). Through 48 h, the proportion of rebleeds was 3.2% (75µg/kg initial dose) and 5.6% (225µg/kg initial dose); the difference between initial dose strategies was not statistically significant. The majority of rebleeds were controlled with a single dose of eptacog beta and no subject who treated a rebleed required hospitalization.

Conclusion: Subjects with haemophilia with inhibitors who used eptacog beta to treat mild/moderate BEs experienced a low incidence of rebleeding. Rebleeds that did occur were effectively controlled with eptacog beta (median, one dose) without the need for hospitalization.

Background: Haemophilia A (HA) is a rare bleeding disorder caused by variants in F8. Although traditional mutational analyses have identified numerous pathogenic variants, the aetiology of HA in certain patients remains unclear. Furthermore, female patients with severe HA are rare.

Aim: To investigate the molecular defects underlying severe HA in two patients and provide personalised reproductive interventions for their families.

Methods: Two patients diagnosed with severe HA without other clinical phenotypes were enrolled in the study. A combination of whole-exome sequencing, real-time quantitative polymerase chain reaction and long-read sequencing (LR-sequencing) was performed to reveal the molecular defects of them, followed by the application of different reproductive intervention strategies.

Results: Proband 1, a 29-year-old man with FVIII activity of 0.8%, did not exhibit common F8 variants, including Inv1 or Inv22, in the coding region. However, he carried a rare maternal novel inversion on ChrX:154148973_154170321, spanning approximately 21.345 Kbp, with breakpoints in introns 13 and 14 of F8. Finally, the couple of Proband 1 opted for assisted reproductive technology using preimplantation genetic testing and successfully conceived. Proband 2, a 20-year-old female with severe HA and FVIII activity of 0.6%, carried inv22 of F8. Further investigation combining whole exome sequencing (WES) and pedigree analysis revealed that she carried a maternal cross-deletion encompassing exons 1-22 of F8, FUNDC2, BRCC3 and CLIC2, along with a de novo missense variant c.5852T>C (p.Leu1951Ser) on her paternal X-chromosome. Chromosome X-inactivation (XCI) analysis demonstrated a highly skewed inactivation of the maternal X chromosome, with a ratio of 98:2. Subsequently, prenatal diagnosis confirmed that the third child in this family did not carry any of the F8 variants present in Proband 2.

Conclusion: Our findings provide novel insights into the genetic aetiology of HA and emphasise the importance of a definitive diagnosis in guiding genetic counselling and personalised reproductive interventions for affected individuals and their families.

Introduction: Physical therapy benefits patients with haemophilia (PWH), but its impact on the health-related quality of life (HRQOL) remains unclear.

Aim: This systematic review and meta-analysis investigated the association of physical therapy, including therapeutic exercise, manual therapy, and physical agent modality, with HRQOL improvement in PWH.

Methods: Databases PubMed, Embase, MEDLINE, and Scopus were searched from inception until April 2024. This review included randomised controlled trials (RCTs) that compare the HRQOL between the physical therapy and control groups. Relevant data and outcome values of included study were collected. Cochrane collaboration's tool and the grading of recommendations, assessment, development, and evaluation approach were used for risk of bias (ROB) and evidence-level assessment, individually.

Results: The systematic review included eight RCTs that involved 298 male PWH. The meta-analysis for HRQOL improvement revealed a significant difference in favour of physical therapy (standardised mean difference [SMD] = .92; 95% confidence interval [CI]:.50-1.33; p < .001). Therapeutic exercise exhibited more benefits in HRQOL improvement than the control groups (SMD = 1.02; 95% CI:.49-1.55; p < .001). Physical therapy effectively improved HRQOL in PWH with better joint status (SMD = 1.74; 95% CI:.97-2.51; p < .001). Of the eight RCTs, six were rated as high ROB. The comparisons revealed a moderate certainty of evidence.

Conclusions: Physical therapy, especially therapeutic exercise, effectively improved the HRQOL of PWH. Maintaining better joint status and timely physical therapy intervention is crucial for HRQOL improvements in PWH. Cautious interpretation is required due to evidence limitations.

Introduction: Acquired haemophilia A (AHA) is characterized by the development of autoantibodies against factor VIII, reducing its activity and potentially resulting in bleeding.

Aim: To assess the characteristics of people with AHA undergoing rehabilitation and/or with low activities of daily living (ADL) scores, thereby characterizing unmet needs in the management of AHA and informing treatment optimization.

Methods: ORIHIME II, the largest epidemiological and treatment survey of AHA in Japan, is a descriptive, retrospective, observational study conducted using health claims data from April 2008 to October 2021. The primary outcome measures were rehabilitation practice and ADL scores on hospital admission and discharge; use of haemostatic agents and immunosuppressive therapy were also assessed.

Results: Overall, 427 patients in Japan were eligible for the study. Median (Q1-Q3) age was 78.0 (70.0-84.0) years; 264 patients (61.8%) were male. Median (Q1-Q3) time to start rehabilitation was 9 (4-21) and 14 (6-31) days for those with an admission ADL score of <85 and ≥85, respectively. Of the 427 patients, 249 underwent rehabilitation. The most common rehabilitation type was for disuse syndrome; haemostatic agents were more commonly used in patients undergoing earlier rehabilitation.

Conclusion: The physical condition of the patient at hospitalization was associated with rehabilitation practice and the ability of the patient to perform day-to-day activities independently. Treatment strategies should be optimized to allow initiation of rehabilitation as early as possible in the course of AHA.

Aim: Heavy menstrual bleeding (HMB) affects up to 37% of adolescents. Given the paucity of available tools to assess health-related quality of life (HRQoL) in adolescents with HMB, we developed the adolescent menstrual bleeding questionnaire (aMBQ), a valid and reliable measure of bleeding-related quality of life. The aim of this study was cross-cultural translation and adaptation of the English aMBQ into French to ensure accessibility for more Canadian adolescents who menstruate.

Methods: A five-step process was followed: (1) forward translation from English to Canadian French; (2) backward translation from French to English; (3) review of source and translated aMBQ to create a reconciled version; (4) cognitive debriefing to ensure linguistic and clinical equivalence and (5) review of cognitive debriefings to produce the final version of the French aMBQ. Results of cognitive debriefings were reviewed after every three participants; items were revised if presented as an issue by ≥2 participants. These changes were implemented and tested in cognitive debriefings until saturation was reached.

Results: Linguistic changes were made to nine (33%) of the questions and one (3.7%) answer options. Major changes were made to four of the 27 questions (15%), and minor changes were made to five of the 27 questions (19%).

Conclusion: Professional translators, clinical experts and patient input through cognitive debriefing are pivotal to successful cross-cultural translation. Results of cognitive debriefing interviews suggest the French aMBQ is easily understood and confirms its face validity.