Haemophilia最新文献

Background: The Natural History Study of the Safety, Effectiveness, and Practice of Treatment for People with Haemophilia (ATHN 7) monitors use of contemporary haemophilia therapies, including emicizumab, a bispecific antibody substituting for activated factor (F)VIII in people with haemophilia A (HA).

Aim: To report participant characteristics and real-world safety and effectiveness of emicizumab in ATHN 7.

Methods: ATHN 7 is a prospective observational cohort study conducted across 26 American Thrombosis and Haemostasis Network (ATHN)-affiliated sites. People with HA receiving emicizumab were eligible for inclusion in this analysis. Clinical information was collected quarterly through participant interview and medical record review. Safety was evaluated by documenting adverse events (AEs); effectiveness was assessed by annualized bleeding rates (ABRs).

Results: At data cut-off (31st December 2023), 257 participants were receiving emicizumab; 63 (24.5%) had FVIII inhibitors at baseline; 84.4% had severe HA. In total, 109 (42.4%) participants were <12 years old. Median (range) emicizumab exposure duration was 116.4 (0.1-206.6) weeks. Overall, 40 AEs were reported in 13 (5.1%) participants; a total of 33 injection-site reactions were reported in 7 (2.7%) participants. No thromboses or thrombotic microangiopathy were reported. There was one fatality from haemorrhagic shock, deemed unrelated to emicizumab. Median (range) ABR for treated bleeds was 0.25 (0-8.18) for participants with FVIII inhibitors and 0.51 (0-16.25) for participants without FVIII inhibitors.

Conclusion: In people with HA treated with emicizumab, no new safety signals were identified. ABRs were similar for participants with or without FVIII inhibitors, across different severities of HA.

Trial registration: ClinicalTrials.gov identifier: NCT03619863.

Background: Limited real-world data exist on recombinant fusion protein-linking coagulation factor IX (FIX) with albumin (rIX-FP) in paediatric previously untreated patients (PUPs) with haemophilia B, particularly in infants.

Aims: To evaluate the treatment patterns, safety and efficacy of rIX-FP in paediatric PUPs in Japan.

Methods: Retrospective chart review of 21 PUPs who initiated rIX-FP between May 2017 and September 2023, with follow-up to June 2024.

Results: At first administration, 95% (19/20) of patients were <2 years old, and 84% (16/19) weighed <10 kg. The mean treatment duration was 27 months. Prophylaxis was received by 90% (18/20), with 56% (10/18) on every 2 weeks and 44% (8/18) on a weekly regimen. The proportion of patients with ≥25 exposure days was 100% in the weekly and 90% in every 2 weeks groups. No patients developed inhibitors or discontinued treatment. Among those on prophylaxis, no bleeding events occurred in patients ≥2 years, while 88% (15/17) of those <2 years experienced superficial perioral, or subcutaneous bleeding, with 2/15 requiring treatment. Every 2 weeks regimen had lower FIX trough levels than the weekly regimen (median: 4% vs. 10%) and a higher annualized bleeding rate (ABR: 8.2 vs. 4.9). The most common bleeding type was traumatic (ABR: 4.8), followed by spontaneous (1.6) and undetermined (0.7). All treated bleeds resolved successfully. In vivo recovery (IVR) positively correlated with body weight in patients <10 kg.

Conclusion: This study provides real-world insights into rIX-FP use in paediatric PUPs, demonstrating its favourable safety, effective prophylaxis, and lower IVR in infants.

Aim: Knee arthropathy affects 90% of patients with severe haemophilia, with unique morphological changes making TKA technically challenging. We evaluated morphological features of haemophilic knees compared to osteoarthritic controls and provide evidence-based surgical recommendations.

Methods: We evaluated 16 haemophilic patients undergoing TKA with 18 gender-matched non-haemophilic OA patients. This represents the largest intraoperative morphometric study of haemophilic knees to date. Morphological indices including femoral mediolateral width (fML), femoral anteroposterior length (fAP), tibial mediolateral width (tML), tibial anteroposterior length (tAP), and intercondylar notch size were assessed using sterile callipers intraoperatively. Clinical correlation with component sizing, surgical technique modifications (femoral component rotation adjustments, modified notch preparation, soft tissue balancing), and early outcomes were analysed.

Results: The haemophilic group exhibited significantly greater fML (78.21 ± 5.34 vs. 70.41 ± 4.34 mm, p = 0.005) and higher aspect ratio (ML/AP: 1.33 ± 0.05 vs. 1.20 ± 0.04, p = 0.03) compared to OA controls. Haemophilic patients had significantly larger intercondylar notch (19.23 ± 1.2 vs. 14.2 ± 1.56 mm, p = 0.03) and more external rotation based on posterior condylar axis (4.1 ± 0.05 vs. 3.2 ± 0.03 degrees, p = 0.03). These differences resulted in component size selection changes in 75% of cases (12/16) and required surgical technique modifications including altered femoral component rotation in 68.75% of cases (11/16).

Conclusion: Haemophilic knees demonstrate distinct morphological characteristics with practical implications for TKA. Modified surgical techniques accommodating wider mediolateral dimensions and altered rotational dynamics can be implemented with existing implants and standard instrumentation. These observations may inform the estimated 1200-1500 haemophilic TKAs performed annually worldwide, though multicentre validation is needed.

Background: Modern prophylaxis in haemophilia aims not only to prevent bleeding but also to ensure a quality of life (QoL) comparable to healthy peers. Real-world data on health-related QoL (HRQoL) in children receiving personalised pharmacokinetic (PK)-guided prophylaxis are limited.

Aim: To compare HRQoL outcomes in Polish children with haemophilia A who switched from standard plasma-derived factor VIII (pdFVIII) prophylaxis to recombinant factor VIII (rFVIII), either as standard or PK-tailored prophylaxis.

Methods: In this nationwide study, 131 boys with severe or moderate haemophilia A were assessed before and ≥26 weeks after switching from pdFVIII to rFVIII. Patients either continued standard prophylaxis (Group 1, n = 28) or started PK-tailored prophylaxis (Group 2, n = 103). Bleeding outcomes (annualised bleeding rate [ABR], annualised joint bleeding rate [AJBR]) and QoL (EQ-5D-5L, Visual Analogue Scale [VAS]) were compared using Student's t-test and Wilcoxon test.

Results: Switching to rFVIII significantly reduced ABR (1.73→0.76; p = 0.004) and AJBR (0.65→0.33; p = 0.009). QoL improved overall, with higher VAS scores (88.6→91.2; p = 0.02) and lower EQ-5D-5L scores (5.78→5.54; p = 0.01). Improvements were most pronounced in Group 2, where both bleeding rates and QoL significantly improved, despite a higher weekly number of i.v. injections. No significant QoL changes were observed in Group 1.

Conclusion: Personalised PK-based rFVIII prophylaxis leads to significant improvements in bleeding control and HRQoL in Polish children with haemophilia A. These results support the integration of PK-guided prophylaxis into routine clinical practice.

Background: Haemophilic arthropathy (HA) is a common complication of haemophilia, characterized by progressive joint degeneration due to recurrent bleeding. Iron overload from erythrocyte lysis is thought to play a key role in HA pathogenesis, but its molecular basis remains unclear.

Methods: We performed data-independent acquisition (DIA) proteomics on synovial tissues from HA, osteoarthritis (OA) and rheumatoid arthritis (RA) patients. Bioinformatics analyses (GO, KEGG, PPI) were used to identify iron-related differentially expressed proteins (DEPs), and selected candidates were validated by Western blot.

Results: Compared to OA and RA, HA synovium exhibited distinct expression patterns enriched in iron metabolism-related pathways, including ferroptosis and porphyrin metabolism. Key DEP such as FTH1 was upregulated, while SLC39A14 was downregulated. PPI analysis highlighted hub proteins involved in iron homeostasis.

Conclusion: This study identifies a unique iron overload-related proteomic signature in HA synovium, suggesting the potential biomarkers in disease progression. These findings provide novel molecular insights and potential targets for early HA intervention.

Introduction: Physiotherapists are irreplaceable in providing safe, tailored physical activity (PA) and exercise in patients with haemophilia (PwH).

Aim: Evaluating physiotherapists' knowledge, self-perceived competence, confidence, role, assumptions for safety of activities and barriers regarding PA and exercise in PwH was aimed.

Methods: A cross-sectional survey was conducted amongst 200 physiotherapists. Knowledge was assessed via a 20-item true/false test. Assumptions for safety were assessed by rating 10 paired physical activities. Self-perceptions and barriers were assessed by the level of agreement with relevant statements.

Results: Participants (median age = 32 years, 69.5% female) had a median of 9 years' experience, predominantly working in orthopaedics; 88% had no prior experience with PwH. Knowledge assessment revealed that the highest correct responses were for items on haemophilia not being contagious and the benefits of exercise (up to 94.5%), while the lowest were for statements regarding joint-specific strengthening, disease severity and resistance training safety (12%-29.5%). Assumptions for safety levels varied substantially across activities. Many participants (87.5%) believe that it is a physiotherapist's duty to determine appropriate PA and exercise for PwH. However, a significant portion of participants reported that they either lack the necessary knowledge, skills or confidence. Patients' and their families' misconceptions about exercise, and insufficient cooperation amongst healthcare professionals, were the most common barriers.

Conclusion: Our study revealed that while physiotherapist recognize their professional responsibility, they feel that they lack the necessary specialized knowledge, skills and confidence. The creation of a specialized, multidisciplinary education program might be beneficial to address this gap.

Introduction: Accurate monitoring of nonacog beta pegol (N9-GP) is essential to ensure appropriate treatment and to avoid under- or overdosing, which may result in clinical complications. The product's extended half-life, achieved through molecular modification, poses challenges for activity measurement, particularly when using a one-stage clotting assay (OSA). Therefore, a chromogenic substrate assay (CSA) is preferred, although it may be less practical for urgent or routine monitoring.

Aim: To evaluate OSA and CSA for N9-GP measurement, focusing on the suitability of the OSA STA CK Prest reagent on the STA R MAX analyser.

Methods: Factor IX activity (FIX:C) of N9-GP in vitro spiked and post-infusion samples were measured using various OSA reagents and CSA across different analysers. The in vitro sample results were evaluated as percentage recovery; the OSA STA CK Prest results from both spiked and post-infusion samples were compared with those obtained by the CSA Biophen FIX.

Results: Acceptable recoveries for samples spiked at concentrations of 0.04, 0.08, 0.15, 0.61 and 1.22 IU/mL were achieved using CSA Biophen FIX (mean recovery 92% with the CN 3000 analyser and 108% with the STA R MAX analyser) and OSA STA CK Prest (mean recovery 92%, range 86%-111%). STA CK Prest showed FIX:C results comparable to Biophen FIX in both in vitro and post-infusion samples.

Conclusions: STA CK Prest and Biophen FIX showed acceptable recoveries for N9-GP, with FIX:C results in good agreement in both in vitro and post-infusion samples. This supports the reliability of STA CK Prest for FIX:C measurement.