Haemophilia最新文献

Introduction: Achilles tendon lengthening combined with external fixation (EF) has shown promising outcomes in managing haemophilia-related Achilles tendon contracture.

Aim: To compare coagulation factor consumption and medium- to long-term outcomes between Achilles tendon lengthening with and without EF.

Methods: Clinical data between December 2012 and April 2023 were retrospectively analysed. Patients were divided into the traditional surgery (TS) group and the EF group based on the fixation method. Inter-group comparisons were performed (p < 0.05 considered significant).

Results: A total of 10 patients completed follow-up. The mean age was 25.8 ± 14.1 years, and the median follow-up duration was 3.17 [1.78, 12.1] years. During hospitalization, mean coagulation factor consumption was lower in the EF group (19.7 ± 11.9 vs. 31.5 ± 9.31 IU/kg*day). One-month post-discharge, consumption was similar (25.2 ± 2.61 vs. 22.3 ± 1.06 IU/kg*day). By the second month, the EF group showed lower consumption (14.3 [13.9, 23.8] vs. 22.6 [20.8, 23.1] IU/kg*day). Additionally, mean intraoperative blood loss was lower in the EF group (104 ± 109 vs. 207 ± 101 mL). The EF group required longer mean fixation times (99 [72.0, 104] vs. 44 [42.0, 54.0] days) and showed a higher complication rate (80% vs. 40%), but all resolved or without impact on daily life. However, one case of contracture recurrence occurred in the TS group. Satisfaction and improvement rates were higher in the EF group (80% vs. 60%). Only the difference in mean fixation time reached statistical significance.

Conclusion: Achilles tendon lengthening with EF may be a safer and effective strategy for managing haemophilia-related Achilles tendon contracture compared to TS. However, further studies are required to confirm these findings.

Background: In India, persons with haemophilia (PWH) are entitled to free diagnostic services, clotting-factor concentrates and physiotherapy. However, families often continue to experience substantial financial hardships for regular treatment. This study aimed to quantify the expenditure borne by such families of PWH treated at our centre and identify contributing factors.

Methods: At our state-supported haemophilia treatment centre, we assessed costs related to travel, wage loss and ancillary diagnostics and medications. A structured questionnaire, adapted from the cost of haemophilia in Europe: A socioeconomic survey (CHESS), was developed, piloted and pretested. Institutional ethics approval was obtained, and informed consent was taken.

Results: Between 2022 and 2023, 250 caregivers out of 800 registered PWH were interviewed. Among the respondents, 74% belonged to lower socioeconomic strata and 38% were daily-wage earners. Approximately 40% travelled > 100 km per bleeding episode. Educational disruption was reported in 5.6% of PWH. Forty-six per cent experienced frequent interruptions; 66% noted adverse effects on siblings' education. While clotting factors were provided free of cost, 61% spent at least ₹500 per visit, with wage losses ranging from ₹500 to ₹5000 per episode. Income loss among caregivers was reported by 85%. Eighty-seven per cent experienced moderate to extreme financial stress. A broader impact on household economics, including food and education, was noted in 69% of families. Only 5% had access to health insurance.

Conclusions: Despite free treatment provisions, haemophilia care imposes a significant financial burden. Prophylaxis with home therapy could mitigate these challenges. Incorporating hidden costs into health economic evaluations is essential for informed policy in resource-limited settings.

Aim: To assess the health-related quality of life (HRQOL) in children with haemophilia A and arthropathy before and after emicizumab prophylaxis using the Canadian Haemophilia Outcomes-Kids' Life Assessment Tool questionnaire Canadian Hemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT) v3.0 and haemophilia family impact tools (H-FIT).

Methods: Eighty-four children with haemophilia A and chronic arthropathy, recruited at Minia University HTC, and their parents/caregivers completed CHO-KLAT and H-FIT questionnaires before and after starting emicizumab. All patients underwent clinical and radiological joint assessments (HJHS, HEAD-US, CHAQ). Only 44 of them were confirmed to have chronic haemophilic arthropathy.

Results: After emicizumab prophylaxis, pain scores decreased significantly (p = 0.0001), while H-FIT scores and CHO-KLAT domain scores (physical activities, bleeding, knowledge, social functioning, treatment, autonomy, environment) increased significantly (p ≤ 0.002 for autonomy/environment; p = 0.0001 for others and total CHO-KLAT). Comparing arthropathic (n = 44) and non-arthropathic (n = 40) patients after initiation of emicizumab, the arthropathic group had significantly higher pain scores and lower H-FIT scores (p = 0.001) but similar total CHO-KLAT scores (p = 0.63). Following emicizumab initiation and implementation of a planned physiotherapy program in the arthropathic group, significant reductions occurred in pain scores, HJHS, HEAD-US, and CHAQ scores (p = 0.0001 for all). No significant correlation existed between the total CHO-KLAT score and HJHS or HEAD-US scores before or after emicizumab administration.

Conclusion: Emicizumab prophylaxis significantly improved HRQoL and reduced joint pain in children with haemophilia A and chronic arthropathy. When combined with a planned physiotherapy program, it further leads to significant improvements in objective joint health outcomes.

Introduction: Efanesoctocog alfa is a novel factor VIII (FVIII) concentrate with a unique molecular design that enables Von Willebrand Factor-independent clearance in patients with haemophilia A. Limited sampling strategies (LSSs) are necessary to implement accurate pharmacokinetic (PK)-guided dosing for efanesoctocog alfa in clinical practice.

Aim: This in silico study aims to evaluate the predictive performance of 10 LSSs with one to three samples for estimating individual PK profiles of efanesoctocog alfa.

Methods: Monte Carlo simulations based on a published population PK model generated individual FVIII activity-time profiles for a virtual population. LSSs were applied to sample from these profiles, and PK parameters, FVIII activity peak level at 0.5 h (C_0.5), FVIII activity trough level at 168 h (C₁₆₈) and time above FVIII activity thresholds (5, 10 and 40 IU/dL) were estimated using Bayesian forecasting.

Results: All LSSs complied with our requirements of a relative mean prediction error of <±5% and a relative root mean square error of <25%. For prophylactic dosing advice, a LSS was considered clinically suitable if at least 80% of predicted C₁₆₈ had a prediction error within -3 to 3 IU/dL. This criterion was met by one two-sample LSS and three three-sample LSSs. For pre-operative dosing advice, suitability required at least 80% of predicted C_0.5 within -20 to 20 IU/dL, fulfilled by one two-sample and six three-sample LSSs.

Conclusions: Several LSSs demonstrated adequate predictive performance for PK-guided dosing of efanesoctocog alfa.

Introduction: Haemophilia B is an X-linked recessive bleeding disorder caused by coagulation factor IX (FIX) deficiency. Treatment involves intravenous replacement of FIX. Recently, extended half-life (EHL) FIX products have been introduced alongside standard half-life (SHL) products to optimize therapy.

Aim: This study evaluated bleeding rates, joint health, factor consumption, dosage, and health-related quality of life (HRQoL) in patients switching from SHL- to EHL-FIX products, as well as in those exclusively treated with EHL-FIX.

Methods: Retrospective data from the medical records of 37 children with haemophilia B treated between 2010 and 2023 at two German Haemophilia Care Centres were analysed. HRQoL was assessed cross-sectionally using haemophilia-specific and generic questionnaires.

Results: Twenty-seven patients (median age: 12 years, range 2-19 years) switched from SHL- to EHL-FIX, while 10 received EHL-FIX from the start of prophylaxis. The mean annual bleeding rate (ABR) improved from 6.01 ± 7.01 (SHL) to 2.85 ± 3.42 (EHL). Factor consumption (159,577.8 ± 99,817.9 IU/year), dosage (118.9 ± 50.3 IU/kg/week) and infusion frequency (145 ± 35.6 infusions/year) decreased after switching (100,247.7 ± 46,268.6 IU/year; 56.4 ± 23.7 IU/kg/week; 55.1 ± 9.8 infusions/year). HRQoL improved in both self-reports and parent reports. No severe adverse events occurred.

Conclusion: Switching from SHL-FIX to EHL-FIX in children with haemophilia B is safe and may improve outcomes by reducing bleeding rates, infusion frequency, and factor consumption while enhancing joint health and HRQoL.

Introduction: The bispecific monoclonal antibody emicizumab was approved for prophylactic treatment of congenital haemophilia A (HA) in Japan in 2018.

Aim: To monitor long-term safety and effectiveness of emicizumab, including appropriate concomitant use of bypassing agents (BPAs), in Japanese patients with congenital HA with inhibitors who initiated emicizumab within 1 year of availability.

Methods: This all-case post-marketing surveillance (PMS) study was conducted between May 2018 and January 2023, in patients of all ages and HA severities. Patients were registered retrospectively after emicizumab initiation or prospectively at the time of initiation. Adverse events (AEs) and adverse drug reactions (ADRs), including thromboembolic events (TEs) and thrombotic microangiopathy (TMA), and their association with BPA use, were examined. FVIII inhibitor levels and annualised bleeding rates (ABRs) were evaluated.

Results: In total, 134 patients were included in the analysis. Mean (standard deviation) duration of emicizumab treatment was 145.5 (34.8) weeks. Overall, 112 AEs occurred in 47 patients (35.1%) and 22 ADRs occurred in 12 patients (9.0%); 8 ADRs (36.4%) were serious. No TEs/TMAs associated with concomitant use of BPAs occurred. FVIII inhibitor levels remained stable or decreased for 34 patients (55.7%). Sixty-eight patients (50.7%) received BPAs; none received activated prothrombin complex concentrate. Mean (95% confidence interval) model-based all bleed ABR and treated bleed ABR were 1.4 (0.9-2.3) and 1.3 (0.8-2.1), respectively.

Conclusion: This study comprises 3 years' PMS for emicizumab. No TEs/TMA associated with BPAs occurred. Results further support the safety and effectiveness of emicizumab in Japanese patients with congenital HA with inhibitors.

Background: Glanzmann Thrombasthenia (GT) is a rare autosomal recessive bleeding disorder characterised by defective platelet aggregation due to abnormalities in the glycoprotein IIb/IIIa complex. With a lack of large real-world database studies, our study aimed to characterise the demographic, clinical and treatment profiles of GT patients using a large, national database.

Methods: A retrospective cohort study was conducted using the EPIC Cosmos database from 1 January 2013 to 31 December 2024. Patients with at least one encounter coded with the SNOMED code for GT (32942005) were included. The primary outcome was the prevalence of GT, calculated using the total database population as the denominator. Secondary outcomes included bleeding manifestations, comorbidities, transfusion utilisation, medication use, sex-based differences and mortality, with statistical comparisons performed using Chi-squared tests.

Results: A total of 1059 GT patients were identified, 58.5% female. The estimated prevalence of GT was 1 in 352,435, higher than prior US estimates. The most frequent bleeding manifestations were abnormal uterine bleeding (29.7% of females aged 11-45), epistaxis (22.6%) and hematuria (16.1%). Anaemia was the most common comorbidity (35.6%), with iron deficiency anaemia present in 31.0%. Transfusion dependency was frequent, with 16.4% of patients requiring blood or component transfusions. No significant sex-based differences were observed. Mortality increased with age, with an overall annualised rate of 1222 per 100,000 GT patients, exceeding that of the general US population.

Conclusion: GT is more prevalent in the United States than previously recognised and is associated with substantial clinical burden from recurrent bleeding, anaemia and transfusion dependency.