INTRODUCTION:Women with von Willebrand disease (VWD) are at increased risk for postpartum hemorrhage (PPH), but contemporary United States data on maternal outcomes and real-world peripartum treatment patterns are limited. AIM:To evaluate maternal outcomes associated with claims-recorded VWD in a national claims cohort and describe exploratory treatment and geozip analyses. METHODS:We retrospectively analyzed FAIR Health claims from 2011-2021. Delivery encounters, VWD, and outcomes were identified using ICD-9/10 codes; laboratory confirmation was unavailable. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for PPH, length of stay above the median, 30-day emergency department visit or readmission, and in-hospital mortality. RESULTS:Among 1,498,768 delivery encounters, 1,514 (0.10%) involved claims-recorded VWD. Overall outcome frequencies were 3.79% for PPH, 24.81% for length of stay above the median, 7.43% for 30-day utilization, and 0.036% for mortality. Claims-recorded VWD was associated with PPH (OR 1.70, 95% CI 1.38-2.10), length of stay above the median (OR 1.58, 95% CI 1.41-1.78), and 30-day utilization (OR 1.20, 95% CI 1.01-1.43), but not mortality (OR 1.79, 95% CI 0.25-12.73). In exploratory analyses, VWF concentrate claims were associated with higher PPH odds versus neither captured desmopressin nor VWF concentrate (OR 3.17, 95% CI 1.28-7.87); desmopressin showed a similar non-significant pattern (OR 3.32, 95% CI 0.93-11.82). CONCLUSION:Claims-recorded VWD was associated with PPH and greater peripartum healthcare utilization. Exploratory treatment associations may reflect confounding by indication, diagnostic misclassification, or treatment timing and cannot establish benefit or harm. Prospective studies incorporating laboratory and clinical data are needed. PLAIN LANGUAGE SUMMARY:Von Willebrand disease is the most common inherited bleeding disorder. For many women, it can cause heavy periods and can also increase the risk of heavy bleeding after delivery, called postpartum haemorrhage. Even though this risk is well recognised, there is still limited information about what happens in real-world delivery care across the United States. In this study, we looked at a large national insurance claims database that included almost 1.5 million delivery encounters from 2011 to 2021. Of these, 1,514 were among women with von Willebrand disease. Compared with women without von Willebrand disease, women with von Willebrand disease had higher odds of postpartum haemorrhage, longer hospital stays, and emergency department visits or readmissions within 30 days of delivery. We also looked at outcomes among women with von Willebrand disease based on whether treatment was documented in the claims data. Women who had claims for von Willebrand factor concentrate or desmopressin had higher observed odds of postpartum haemorrhage than women without documented treatment. This does not mean that the treatment caused bleeding. More likely, these women were treated because they were already considered to be at higher risk, had more severe disease, were actively bleeding, or raised greater concern for their clinical team. Overall, this study shows that postpartum bleeding remains an important and ongoing issue for women with von Willebrand disease. Future studies should include laboratory results, bleeding history, details about treatment timing and dose, delivery setting, and access to specialised bleeding disorder care. These details are needed to better understand which patients are at highest risk and how to improve the prevention of postpartum haemorrhage.
INTRODUCTION:Accurate laboratory diagnosis is essential for the effective management of bleeding disorders. The World Federation of Hemophilia (WFH) International External Quality Assessment Scheme (IEQAS) provides an international platform for comparative evaluation of laboratory performance. AIM:To evaluate global laboratory performance in the diagnosis and monitoring of bleeding disorders, and to assess the impact of training and capacity-building initiatives on laboratory quality. METHODS:We conducted an analysis of data from 268 laboratories in 114 countries participating in the WFH IEQAS program between 2016 and 2023. RESULTS:The proportion of countries with at least one participating laboratory was 71% in the Americas, 65% in Africa, 54% in Asia, 50% in Europe, 28% in the Middle East, and 7% in Oceania. Most laboratories were in upper-middle-income countries. Across all surveys, only 50% of factor VIII activity assay results fell within the expected target range. Oceania demonstrated the highest rate of consensus (78%, based on two laboratories), followed by Asia (58%), the Americas (53%), and Europe (53%). Longitudinal analysis revealed progress in Africa and the Middle East. Two hemophilia center laboratories monitored over seven years following training showed divergent outcomes: one sustained improvement, while the other achieved only transient gains. CONCLUSIONS:Substantial variability persists in global laboratory performance for bleeding disorder diagnostics, with marked regional disparities. Improvements in Africa and the Middle East demonstrate the positive impact of targeted training and capacity-building. The WFH IEQAS program provides a robust framework for comparative evaluation laboratory performance and guiding interventions to strengthen diagnostic capacity worldwide.
INTRODUCTION:Emicizumab is a bispecific antibody approved for prophylaxis in people with haemophilia A (PwHA). AIM:To describe from the physician perspective the characteristics and treatment experiences of PwHA receiving emicizumab. METHODS:The Adelphi Real World Haemophilia Disease Specific Programme is a cross-sectional, retrospective data collection from US haematology and haematology-oncology specialists between July 2023 and April 2024. Male PwHA with or without inhibitors were included if they had baseline factor VIII levels <5% and were not currently participating in a clinical trial. Surveys captured demographic characteristics and clinical outcomes, including bleeding events. RESULTS:Fifty-four physicians provided data for 293 PwHA, of which 115 were seen outside federally funded haemophilia treatment centres (HTCs), 77 were treated with emicizumab and 49 had pre- and post-emicizumab initiation data available. More Black, African American, African or Caribbean PwHA received emicizumab outside federally funded HTCs than at federally funded HTCs (46.2% vs. 16.7%). Most emicizumab doses were taken on time (mean [SD], 90.7% [14.6%]), and 64.0% of PwHA took >80% of the prescribed dose. More PwHA had zero treated bleeds (76.9% vs. 42.9%), with fewer bleeding events (mean [SD], 1.3 [1.9] vs. 0.4 [1.1]; p = 0.0001) during the post-emicizumab period (median [IQR] follow-up, 12.0 [1.3-12.0] months) than in the 12 months pre-emicizumab. Post-emicizumab outcomes were similarly improved across settings, whether at federally funded HTCs or elsewhere. CONCLUSION:Among PwHA receiving emicizumab, rates and severity of bleeds decreased after emicizumab initiation, regardless of the clinical setting.
Psychosocial care is a critical component of comprehensive haemophilia management, though its availability varies across regions and between clinical and community settings. This paper examines the landscape of psychosocial services offered through Haemophilia Treatment Centres (HTCs) and National Member Organizations (NMOs), both of which promote mental health, treatment adherence, and quality of life (QoL) using different frameworks. The delivery of psychosocial care in clinical settings, including staffing models, training, and collaboration with other healthcare professionals, is described in this paper, as are the differences between high-income and low- and middle-income countries. We explore how socioeconomic factors, gender, and cultural context influence haemophilia care and consider the future of psychosocial care needs related to novel therapies such as gene therapy and extended half-life products. The paper concludes by advocating for integrated psychosocial care that adapts alongside biomedical advances, addresses global inequities, and emphasizes a patient-centred, culturally informed approach to treatment.
INTRODUCTION:Understanding patients' and caregivers' experiences, values and needs is essential to implement patient-centred care. However, specific insights into how young children with haemophilia and their caregivers experience the entire care trajectory, from diagnosis onwards, remain limited. AIM:Gain an in-depth understanding of the experiences and needs of caregivers of young children (0-10 years) with haemophilia regarding haemophilia care and daily life, as well as children's own perspectives. METHODS:A qualitative interview study was conducted applying purposive sampling to select a varied sample regarding haemophilia type, disease severity, treatment modality and the child's age. Interviews were conducted until saturation was reached, followed by a comprehensive thematic content analysis including multiple phases of coding. RESULTS:In total, 27 interviews were conducted (38 caregivers, 15 children). Twenty-five subthemes emerged related to four care pathway phases, and daily life. Caregivers emphasized that haemophilia knowledge among healthcare providers outside treatment centres, information provision, access to peer support and remote healthcare can be improved. Haemophilia had psychological, social and occupational impacts on caregivers. Impact on daily life was variable and primarily influenced by bleeding phenotype, and family history. Lastly, caregivers highlighted the importance of child-centred care, maintaining haemophilia awareness and the benefits of prophylaxis and self-administration. CONCLUSION:To further enhance patient-centred care, caregivers expressed the need for a tailored and centrally available information resource, expansion of remote healthcare services and increased haemophilia knowledge. Furthermore, healthcare providers should be more aware of the multifaceted impact of haemophilia on caregivers and the factors influencing haemophilia impact on daily life.
INTRODUCTION:Prior authorizations (PAs) are widely used to control healthcare costs and ensure appropriate use of high-cost therapies, but they often create undue administrative burdens. In haemophilia care, timely access to specialty medications is critical, yet Haemophilia Treatment Centres (HTCs) must frequently navigate payer-driven PA requirements that can delay treatment and disrupt care delivery. To our knowledge, this study is the first of its kind to examine how the PA process affects patient care and provider workloads in HTCs METHODS: Twenty staff from federally designated HTCs across the United States were purposively recruited to participate in virtual, semi-structured interviews. Eligible participants were directly involved in the PA process. Interviews were recorded, transcribed, and de-identified. Data were analyzed using conventional content analysis with independent coding by two investigators, supported by Dedoose software. Descriptive statistics summarized participant characteristics, and the labour-time and cost estimate was estimated by annualizing labour costs using mean weekly hours spent on PAs and position-specific wage rates. RESULTS:A thematic analysis revealed four themes related to PA challenges and the burden on care delivery. The mean weekly time spent on PAs was 6.5 h per participant. Eighty-five percent of participants reported burnout related to PAs. The labour-time and cost estimate per participant-year spent on PAs ranged from $4795 (nurse practitioner) to $20,718 (non-clinical staff). CONCLUSION:The findings emphasize the need for efficient, clinically informed PA processes to reduce administrative burden and care delays, and identify a need for further education for insurers, potentially at the national level.
INTRODUCTION:Patients with von Willebrand disease (VWD) undergoing surgery require von Willebrand factor (VWF) and factor VIII (FVIII) supplementation for adequate haemostasis. Plasma-derived clotting factor concentrates differ in their VWF:FVIII activity ratios: high-ratio product (HRP, 10:1), intermediate-ratio product (IRP, 2.4:1), and low-ratio product (LRP, 1:1). These differences may affect FVIII kinetics. METHODS:This single-centre observational study included VWD patients undergoing surgery, treated with an HRP, IRP, or LRP, and with ≥2 perioperative VWF or FVIII measurements between 2009 and 2024. VWF and FVIII trajectories were assessed using linear mixed-effects models. Secondary endpoints were bleeding and venous thromboembolic events (VTE). RESULTS:In total, 123 patients were included; 63% underwent major surgery. Twenty-four patients received HRP, 61 received IRP and 38 received LRP. The median number of infusions was three across groups. Incremental VWF recoveries were 1.7 IU/dL per IU/kg for HRP, 1.3 for IRP, and 2.4 for LRP. FVIII recoveries were 2.5 for IRP and 2.7 for LRP. Over time, HRP showed higher mean VWF levels than IRP (Δ26 IU/dL; p = 0.010). HRP was associated with higher FVIII levels compared with IRP (Δ48 IU/dL; p < 0.001) and LRP (Δ35 IU/dL; p = 0.021). No difference was found between IRP and LRP. In patients receiving three consecutive infusions in 24 h, FVIII levels remained higher with HRP than IRP (Δ38 IU/dL; p = 0.019). No VTEs occurred. CONCLUSION:IRP and LRP led to greater initial VWF and FVIII peaks, whilst HRP produced more sustained FVIII elevation. Recognising these kinetic differences may guide tailored perioperative management of patients with VWD.
INTRODUCTION:National registries are essential infrastructure for haemophilia and allied bleeding disorders, but registry development and international alignment across the Asia-Pacific region remain unclear. AIM:To evaluate the availability, governance, technical infrastructure, international engagement, and patient-facing digital functions of national haemophilia registries across the Asia-Pacific region. METHODS:The AHAD-AP Registry Committee conducted a structured survey of Country/Region/Territory (CRT) representatives. The questionnaire assessed registry status, funding and governance, international alignment, technical infrastructure, data-entry methods, and digital functions. Multiple responses from the same CRT were harmonized when needed. RESULTS:Nineteen individual responses representing 15 CRTs were consolidated into 15 CRT-level responses. Ten CRTs reported an active national registry, one a planned registry, three no national registry, of which two had centres participating in World Bleeding Disorders Registry (WBDR), and one hospital-based registry. Haemophilia was included in all, while VWD and other inherited coagulation factor deficiencies were included in 11 of 12. Mandatory registration was reported by 5 CRTs. Funding and governance structures varied across CRTs. Awareness of WBDR was reported by 12 of 15 CRTs, while dataset alignment, data submission, and technical integration were reported by 8, 4, and 1 CRTs, respectively. Manual data entry remained common (9/12), and patient-oriented digital functions, including infusion logs or related support tools, were reported by 10 of 12 registries. CONCLUSION:This survey represents the first large regional assessments of national haemophilia registry infrastructure across the Asia-Pacific region. Harmonized datasets, sustainable governance, technical integration, and patient-facing digital tools may support future registry development.
INTRODUCTION:Bone health impairment is an important but underexplored complication in pediatric haemophilia. This study aimed to evaluate bone remodelling imbalance by integrating bone mineral density (BMD), osteoclastogenic markers, Wnt signalling inhibitors, and mineral metabolism parameters. METHODS:A case-control study was conducted, including children with haemophilia not receiving routine factor prophylaxis and age-matched healthy controls. Lumbar spine BMD was assessed. Serum levels of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), sclerostin, and Dickkopf-1 (DKK1) were measured. The osteoclastogenic index (RANKL/OPG ratio) was calculated. Serum calcium, phosphorus, alkaline phosphatase (ALP), parathyroid hormone, and vitamin D levels were also analysed. Regression and receiver operating characteristic (ROC) analyses were performed. RESULTS:Haemophilia children with high AJBR (22.55 ± 18.84) and not receiving routine prophylaxis exhibited significantly lower lumbar spine BMD than controls. RANKL levels and the osteoclastogenic index were significantly elevated, while OPG levels showed no significant change, indicating enhanced osteoclast activity. Sclerostin levels were significantly increased, whereas DKK1 showed a non-significant rise, suggesting suppression of Wnt-mediated bone formation. Calcium, phosphorus, and ALP levels were significantly reduced, reflecting impaired mineralisation. The osteoclastogenic index showed a significant negative association with BMD and demonstrated excellent diagnostic performance on ROC analysis. CONCLUSION:Bone loss in children with haemophilia with high AJBR and not receiving routine prophylaxis is characterised by increased bone resorption, decreased bone formation, and impaired mineralisation. The osteoclastogenic index may serve as a robust biomarker for early detection and risk stratification of skeletal complications.
INTRODUCTION:Haemophilia is a rare congenital bleeding disorder that presents significant physical and psychological challenges, especially for young people, with limited real-world evidence about their experiences in the UK. AIM:This study sought to understand the perspectives and challenges of young people living with haemophilia in the UK by analysing social media conversations. METHODS:A retrospective qualitative study using social media listening was conducted, analysing publicly accessible UK-based posts from September 2021-September 2024. Data collection and thematic analysis focused on posts from people with haemophilia and their caregivers, with particular attention to the 13-25 age groups. RESULTS:Out of 47,239 relevant posts identified, 839 were selected for in-depth qualitative analysis. An artificial intelligence-powered natural language processor, CoLoop, was used to identify five main themes: 'care and management' (83.54% of posts in the 13-25 cohort), 'living with haemophilia' (61.59%), 'social aspects of haemophilia' (31.10%), 'advancements and future outlook' (11.59%), and 'genetic considerations and family planning' (7.93%). Overall, the results demonstrated that young people with haemophilia in the UK seek greater independence, emotional resilience, and tailored support, highlighting the value of patient-centred care, digital engagement, and policy reforms to address both clinical and psychosocial needs. CONCLUSION:This study underscores the importance of supporting healthcare professionals in deepening their understanding of their patients' lived experiences of haemophilia to provide comprehensive care. Social media listening offers a novel, measurable approach for identifying the challenges and unmet needs faced by patients with haemophilia.
INTRODUCTION:The severity of haemophilia A is classified by the degree of factor VIII (FVIII) deficiency, rather than by clinical manifestations. However, FVIII activity alone does not necessarily accurately reflect clinical severity such as bleeding tendency, and patients with mild-to-moderate haemophilia A can experience significant disease burden. AIM:This narrative review explores the clinical relevance of non-severe haemophilia A (focusing on moderate disease), and examines the profile of patients with, and the evidence supporting the use of prophylaxis to manage, this disease form. METHODS:A PubMed search was conducted (no language/date limits), using terms including 'hemophilia' or 'haemophilia', and 'moderate', 'nonsevere' or 'non-severe', with the names of prophylactic agents. RESULTS:Some patients with moderate haemophilia A experience significant disease burden (in terms of bleeding frequency and joint damage), diminished health-related quality of life and marked economic impact. In addition, variation in bleeding phenotype across disease severity levels has been recognised, such that patients with moderate disease may have a severe phenotype and experience more frequent spontaneous bleeds than those with a mild phenotype. Few studies have specifically assessed outcomes associated with prophylaxis in patients with moderate haemophilia A. However, available data suggest that prophylaxis with FVIII concentrates and non-factor treatments (i.e. emicizumab) provides beneficial effects in terms of bleeding frequency and joint health. CONCLUSION:Severity classification alone is insufficient to predict bleeding tendency, and joint bleeding and joint injury are observed in patients with moderate disease. As such, routine prophylaxis may be recommended for some patients with moderate haemophilia A.
INTRODUCTION:Real-world data on health-related quality of life (HRQoL) and its predictors in people with haemophilia (PWH) are crucial to evaluate the effect of comprehensive management. It may be useful for clinicians and interdisciplinary teams to better target their interventions. We aimed to characterise global HRQoL and its associated factors in PWH within the Colombian health system. METHODS:A cross-sectional study on PWH included in the Colombian Registry of Haemophilia and other Coagulopathies (CRHOC) from November 2021 to April 2022. Global HRQoL was measured using culturally validated versions of HemoLatin-QoL (adults) and CHO-KLAT 2.0 in children and their parents. A descriptive analysis and simple and multiple linear regressions were used to identify the factors associated with global HRQoL. RESULTS:Five hundred and eighty-three participants were analysed (452 adults and 131 children). A total of 93% were men with a median age of 36 years (IQR: 27-51) in adults and 12 years (IQR: 9-15) in children. Most people were affiliated with the contributory insurance scheme, 98% of children were students, and 63% of adults were employed. A total of 79% had haemophilia A, 44% of adults and 63% of children had a severe form, and prophylaxis was the most used treatment. Median HRQoL was 83 points (IQR: 65-95) in adults and 72 points (IQR: 63-81) in children. In both subpopulations, experiencing pain, haemarthrosis and belonging to the subsidised insurance scheme worsened HRQoL. In adults, higher education, being employed or a student, physical activity, and being treated with Emicizumab significantly improved HRQoL. Prophylaxis had a significant protective effect in adults with severe disease. CONCLUSION:Pain, haemarthrosis and being affiliated with the subsidised scheme negatively modified HRQoL in adults and children. Prophylaxis improved HRQoL in severe cases. These findings help clinicians to better focus interdisciplinary management according to patient self-reported outcomes.
INTRODUCTION:Various extended half-life recombinant factor VIII (EHL-FVIII) products have been designed to improve the pharmacokinetic properties of FVIII, allowing prolonged haemostatic coverage and reducing the injection burden in people with haemophilia A. Nevertheless, the influence of direct molecular attachment on fibrin clot formation and stability remains to be investigated. AIM:To investigate the stability and architecture of fibrin clots in the presence of various types of EHL-FVIII. METHODS:Three EHL-FVIII products with direct attachment modifications (damoctocog alfa pegol, efraloctocog alfa, and rurioctocog alfa pegol) and two standard FVIII (turoctocog alfa and rurioctocog alfa) were added to FVIII-deficient whole blood and plasma at various concentrations for functional comparison. Under whole-blood conditions, functional assays were performed using rotational thromboelastometry (ROTEM) and a microchip flow-chamber system (T-TAS). Under plasma-based conditions, fibrin fibres were directly observed by electron microscopy and coagulation function was assessed using clot waveform analysis (CWA). Anticoagulant and fibrinolytic activities were evaluated by CWA with the addition of activated protein C and tissue plasminogen activator, respectively. RESULTS:At equivalent activity levels, none of the assays revealed significant differences among the three EHL products or the two standard products. All contributed comparably to fibrin clot formation and stability, as well as to anticoagulation and fibrinolysis functions. CONCLUSION:Direct modification by PEGylation or IgG-Fc fusion to impart EHL characteristics preserves the functional properties of native FVIII. PLAIN LANGUAGE SUMMARY:People with haemophilia A require treatment with factor VIII (FVIII) to prevent or control bleeding. Some FVIII products are designed to remain active in the body for a longer time, which can reduce the number of injections needed. This extended half-life is achieved by chemically or biologically modifying FVIII, for example by attaching polyethylene glycol (PEG) or the Fc portion of immunoglobulin G. These treatments are known as extended half-life FVIII (EHL-FVIII) products. However, it has not been fully established whether these modifications affect how blood clots form and remain stable. In this study, we compared three EHL-FVIII products with two standard FVIII products using FVIII-deficient blood and plasma. We evaluated clot formation and stability using several laboratory techniques, including whole-blood assays and scanning electron microscopy. We also examined potential differences in anticoagulant and fibrinolytic properties. At comparable FVIII activity levels, we observed no major differences between the EHL-FVIII products and the standard FVIII products in any of the assays performed. These findings suggest that PEGylation or Fc fusion, which are used to extend the half-life of FVIII, do not impair its functional properties related to fibrin clot formation and stability.
INTRODUCTION:Haemophilia B (HB) associates with deleterious variants in F9. HB management with FIX-concentrate infusions may be ineffective in 3%-9% patients who develop FIX-inhibitors. AIM:To present our HB-series (n = 136) including all Argentinean patients with FIX-inhibitors (n = 13). To estimate F9-genotype-associated FIX-inhibitor risks from our series (GMH), and HB-international databases, FIX-UCL and EAHAD. METHODS:F9-genotyping was performed by conventional protocols; or by short-read-NGS on a new F9-panel. FIX-inhibitor risks were estimated by case(inh+)/control(inh-) studies using OR(95%CI). RESULTS:The spectrum of F9-genotypes from our GMH-series resulted similar to the one compiled in international databases, prevailing missense (45%), and nonsense (21%) in severe-HB and missense defects (> 80%) in non-severe-HB. Our set of HB-patients with FIX-inhibitors mostly included large-deletions and nonsense mutations, and 38.5% developed allergic reactions. Case/Control studies mainly aligned FIX-inhibitor risks in all three datasets. Considering severe-HB in GMH(n = 91)//FIX-UCL(n = 349)//EAHAD(n = 590), we observed a high-risk group that comprised entire-F9-deletions with highly-significant ORs of 24//12//35, all-large-deletions, 7//7//17 and nonsense mutations, 3//3//2; and a low-risk group confined to missense F9-variants with highly-significant protective ORs, 0.04//0.11//0.03, whilst other F9-variants did not differ from the null-hypothesis. Equal analysis from all-severities HB patients closely agreed with these results. An analysis of NS and FIX-inhibitor risks suggested the involvement of nonsense-mediated decay (NMD) in F9: nonsense (F9-exons_1-7) vs nonsense (F9-exon_8) resulted in highly-significantly incremented risks in both FIX-UCL(n = 124)//EAHAD(n = 171), ORs of 4(2-9)//4(3-6). CONCLUSION:Our study provides robust estimations of F9-genotype-associated FIX-inhibitor risks in HB-patients and exposed the involvement of NMD.
