Exercise-based telerehabilitation for the management of chronic pain in people with severe haemophilia: a mixed-methods feasibility study.

BACKGROUND: Chronic pain is reported by between 30 and 71% of people with haemophilia (PWH). Exercise is shown to be effective for pain management in other arthritides, but it remains unclear if such an approach is effective or acceptable to PWH. The aim of this study was to evaluate the feasibility and acceptability of a telerehabilitation exercise intervention for PWH living with chronic pain. METHODS: This was a multisite, non-randomised, pre-post feasibility design, with a nested qualitative study. People with severe haemophilia > 18 years, living with chronic pain, were recruited. The intervention comprised 12 low-impact/moderate intensity, individualised exercise sessions and 3 knowledge-sharing and discussion sessions. Primary objectives assessed according to predefined progression criteria were as follows: (a) recruitment rate (5 participants enrolled per site over 8 weeks), (b) adherence (≥ 75% participants would adhere to ≥ 75% of sessions), (c) follow-up rate (≥ 75% completion of self-reported measures), (d) fidelity (intervention delivered as described in protocol) and (e) safety (≤ 30% participants would report adverse events). Acceptability was evaluated from thematic analysis of post-intervention participant interviews. Preliminary evaluation of self-reported pain, function and quality of life (QoL) was a secondary objective. Results were reported using descriptive statistics integrated with qualitative findings. RESULTS: Ten PWH were recruited and completed the intervention. Nine agreed to be interviewed post intervention. Attendance at individual sessions was 84.5% compared to 52.1% for the group sessions. Outcome measures were successfully completed for 100% at baseline, 70% at intervention end and 60% at 3-month follow-up. No serious adverse events were recorded. Group median values in outcome measures (pain, function, QoL) showed minimal change post intervention. Participant interviews highlighted high levels of enjoyment, confidence in continuing exercises independently and positive views of virtual delivery and condition-specific exercise. CONCLUSIONS: Recruitment rate and safety met the predefined progression criteria. Fidelity partially met the progression criteria, but the follow-up rate for self-reported measures did not. The study was acceptable to both participants and physiotherapists. Further intervention development is needed to review approaches to outcome measure collection and refine the usefulness of the knowledge-sharing sessions. TRIAL REGISTRATION: The study was prospectively registered on 9 July 2021: International Standard Randomised Controlled Trial Number ISRCTN 17454597.

Development of the World Federation of Hemophilia Shared Decision-Making Tool.

INTRODUCTION: The use of shared decision-making (SDM) in clinical settings is becoming more prevalent. The evolving and increasingly complex treatment landscape of haemophilia management has augmented the need and desire for SDM between patients and their healthcare team. SDM tools have been used in other chronic conditions and can be an effective form of education for patients and clinicians. AIM: The World Federation of Hemophilia (WFH) partnered with people with haemophilia (PWH), patient advocacy groups, and healthcare practitioners to form an expert working group to develop an educational tool for PWH and their caregivers. The primary objectives included educating PWH on the available prophylactic treatments and facilitating discussion between PWH and their healthcare team. METHODS: The tool was proposed and developed by the expert working group, workshopped at conference round tables, and evaluated in two focus groups. RESULTS: The interactive WFH SDM Tool guides users through the SDM treatment journey and provides an opportunity for reflection on current disease impact and treatment preferences, educational fact sheets and videos, and a comparison between treatment classes. Two forms of the SDM Tool are available: an online platform with a summary page that may be printed and shared and a printable workbook. All evidence in the tool is based on the prescribing information or phase III clinical trial publications. The Tool will be updated twice each year. CONCLUSION: The WFH SDM Tool is the first available resource that translates published guidance on SDM in haemophilia into a practical, user-friendly tool aimed at facilitating patient-centred treatment decisions.

Current Diagnosis of Bleeding Disorders in Lower Income Countries.

There have been considerable advances in diagnosing and treating bleeding disorders. But the scenario remains dismal in resource-constrained settings in low and lower-middle-income countries (LMICs). Seventy-five percent of the patients with inherited bleeding disorders do not get diagnosed in LMICs. In resource-constrained settings, infectious disease and malignancies take the major focus. Bleeding disorders do not get prioritised in LMICs, and this leads to underdiagnoses and suboptimal treatment. There are various challenges like financial status, inadequacy of health care infrastructure, lack of patient registry and lack of awareness across medical staff, general population and government stakeholders. The lack of skilled laboratory personnel and laboratory infrastructure for optimal bleeding disorder diagnosis adds on to the problem. World Federation of Hemophilia (WFH) has been at the forefront in developing strategies to overcome some of these inadequacies; however, more active participation of the stakeholders including patients, medical professionals and policy makers is the need of the hour. This review highlights the different challenges in LMICs in diagnosing bleeding disorders, the gap between high-income countries and LMICs and the possible strategies in closing the gap.

Haemophilia testing of young girls in Canada: Describing the current recommendations for factor level and genetic testing and the experiences of Canadian parents.

INTRODUCTION: It is widely acknowledged that haemophilia affects women and girls, yet current testing recommendations for factor level and genetic testing vary and do not universally incorporate updated research. Canadian parents have expressed frustration at inconsistent recommendations and reported instances where delayed testing led to missed diagnosis and preventable bleeding. AIM: Study aim was to explore and describe the practice of haemophilia-related testing of young girls in Canada. METHODS: A mixed methods study was carried out with two populations: (1) Nurses working in haemophilia care completed a survey regarding the current testing recommendations of their Haemophilia Treatment Centre (HTC), (2) Parents of obligate or potential haemophilia carriers completed a structured interview with questions about their family experience of haemophilia and testing decisions for daughters. RESULTS: Twenty-six survey responses were received and showed wide variation in the usual recommendations of Canadian HTCs. Different factor level testing recommendations may be given to obligate and potential carriers despite no difference in bleeding risk. Only a minority of HTCs currently recommend an early baseline factor level (< 10 years) to obligate carriers (27%) or potential carriers (15%). For genetic testing of potential carriers, 70% of HTC would approve a family request for genetic testing of a minor with specific conditions. The majority of parents interviewed felt dissatisfied with their testing experience (58%) and highlighted many issues related to delayed testing recommendations. CONCLUSION: Updated, nationally affirmed testing recommendations are needed that align with research on bleeding in women and girls affected by haemophilia.

Evaluating the benefits of emicizumab prophylaxis for haemophilia A with inhibitors: A cost-effectiveness and budget impact analysis in Thailand's upper-middle income setting.

BACKGROUND: In Thailand, an upper-middle-income country, managing haemophilia A (HA) with inhibitors poses significant challenges, often necessitating bypassing agents (BPAs) for bleeding control. This study evaluates the cost-effectiveness and budget impact of emicizumab, a novel prophylactic agent, as an alternative to both episodic and prophylactic BPA treatments from a societal perspective. METHODS: A Markov model was employed to estimate the lifetime societal costs and outcomes of emicizumab prophylaxis for HA patients with inhibitors. Treatment efficacy, cost, and epidemiological data were obtained through a comprehensive literature review and incorporated into the model. A 5-year budget impact analysis complemented the cost-utility analysis, with a 3% annual discount rate applied to future costs and outcomes. RESULTS: In the base-case scenario, emicizumab prophylaxis in HA patients aged 2 years and above demonstrated superior cost-effectiveness, yielding 18.1 quality-adjusted life years (QALYs) per patient over a lifetime and resulting in cost savings of 138 million Thai Baht (THB) compared to BPA prophylaxis. Compared to episodic BPA treatment, emicizumab yielded 30.5 QALYs and saved 25 million THB per patient. The 5-year budget impact was projected at 1775 million THB. CONCLUSIONS: Emicizumab offers a cost-saving approach for HA treatment with inhibitors in Thailand, promising significant health benefits and budgetary savings. This supports its potential inclusion in Thailand's National List of Essential Medicines to enhance haemophilia care access. HIGHLIGHTS: Managing haemophilia A (HA) with inhibitors in Thailand, an upper-middle-income country, faces challenges due to limited access to effective treatments or newer drugs for bleeding management. Emicizumab prophylaxis found to as a cost-effective and viable alternative to traditional treatments, effectively preventing bleeding in Thai HA patients over 2 years old with inhibitors. Demonstrating improved clinical outcomes and reduced costs, emicizumab prophylaxis outperforms episodic BPA treatments, positioning it as a superior treatment option for HA patients with inhibitors in Thailand.

Adherence and Quality of Life in Adult Patients With Haemophilia A, Haemophilia B and Von Willebrand Disease: A National Cross-Sectional Survey.

BACKGROUND: New treatments for patients with bleeding disorders (PWB) have emerged, including products with extended half-life and subcutaneous administration. These less frequent treatments can potentially enhance quality of life (QoL), but adherence becomes critically important. AIM: To investigate adherence and QoL among PWB and explore the correlation between treatment adherence and QoL in adult patients with haemophilia A (HA), haemophilia B (HB) and Von Willebrand disease (vWD) in Denmark. METHOD: This survey used disease-specific patient-reported questionnaires: Veritas-PRO and Veritas-PRN to measure adherence, and Haemo-A-QoL and VWD-QoL to assess QoL. RESULTS: Responses were obtained from 149 patients with HA, 32 with HB and 118 with vWD. Adherence was reported by 87.1% of patients on prophylaxis and 71.2% of patients treated on demand, according to Veritas-PRO and Veritas-PRN cut-off scores. High QoL was generally reported, decreasing with age in HA and HB, but not in vWD. CONCLUSION: Danish patients with HA, HB and vWD reported high QoL and high adherence to prescribed treatments. There was no correlation between treatment adherence and QoL among the different patient groups. These findings highlight the need for further research to better understand adherence behaviours and identify opportunities to further improve QoL in PWB.

Value contribution of etranacogene dezaparvovec gene therapy in moderately severe and severe haemophilia B through multi-criteria decision analysis.

INTRODUCTION: The value of gene therapies for haemophilia needs to be assessed holistically. AIM: To determine the value of etranacogene dezaparvovec (ED) compared to current extended half-life (EHL) recombinant factors (rFIX), using multi-criteria decision analysis (MCDA). METHOD: MCDA EVIDEM methodology adapted to orphan drugs was used, with nine quantitative criteria and four contextual criteria. The MCDA framework was rated by 28 multidisciplinary experts. Descriptive statistics were performed for quantitative and qualitative criteria. RESULTS: Haemophilia B (HB) was considered a severe disease (mean ± SD: 4.3 ± 0.7) with some unmet needs (mean ± SD 3.3 ± 0.9). Experts found ED more effective (mean ± SD 2.0 ± 2.3) and provide better quality of life (QoL) (mean ± SD: 1.8 ± 1.5) than the comparative HB treatments but with safety uncertainties (mean ± SD -1.2 ± 1.8). ED could lead to medical cost and non-medical cost savings over time (mean ± SD: 1.6 ± 2.0 and 2.0 ± 1.5, respectively). The quality of the evidence was high (mean ± SD: 3.9 ± 0.9). ED was considered aligned with the priorities of the National Health System (NHS) and the specific interests of patients. ED's value contribution was 0.45 (+1 = highest value). CONCLUSIONS: ED brings added value in the treatment of moderately severe and severe HB (sHB) compared to current EHL rFIX, addressing the severity of the disease and increasing efficacy and patients' QoL especially related to the single dose and low bleeding rate. Concerns about long-term safety need to be addressed.

Invasive procedures and surgery following etranacogene dezaparvovec gene therapy in people with haemophilia B.

BACKGROUND: Little information regarding the management of invasive procedures in people with haemophilia B (HB) after undergoing gene therapy is available. Here, we report the management of invasive procedures in people with severe or moderately severe HB who had previously been treated with etranacogene dezaparvovec in the Phase 2b and Phase 3 HOPE-B clinical trials (NCT03489291, NCT03569891). METHODS: This retrospective analysis included invasive procedures performed within 3 and 2 years following a single infusion of 2x1013 gc/kg of etranacogene dezaparvovec in participants in the Phase 2b and HOPE-B trials, respectively. Data for FIX dosing, duration of postoperative FIX use, FIX activity prior to invasive procedures, and postoperative bleeds were collected and analysed. RESULTS: The analysis included 64 procedures in 29 participants: nine major surgeries, 24 minor surgeries, 11 endoscopies, three endoscopies with biopsy/polypectomy, and 17 dental procedures. Uncontaminated endogenous FIX activity corresponded to mild haemophilia or normal levels prior to 98% of all procedures, with a median endogenous FIX activity of 43.8 IU/dL (range 3.1-113 IU/dL). All major surgeries were managed with exogenous FIX, 67% with ≤4 days of FIX infusion. Most minor surgeries (88%), endoscopies (82%), and dental procedures (94%) were managed with no or a single FIX infusion. Postoperative bleeds occurred after one minor surgery and four dental procedures. There were no symptomatic thrombotic events or FIX inhibitor developments. CONCLUSION: Etranacogene dezaparvovec has the potential to facilitate perioperative management in people with HB by reducing the need for perioperative exogenous FIX and its associated risks.

MR Imaging of Hemosiderin Deposition in the Ankle Joints of Patients with Haemophilia: The Contribution of a Multi-Echo Gradient-Echo Sequence-Correlation with Osteochondral Changes and the Number and Chronicity of Joint Bleeds.

We aim (a) to introduce an easy-to-perform multi-echo gradient-echo sequence (mGRE) for the detection of hemosiderin deposition in the ankle joints of boys with haemophilia (b) to explore the associations between the presence and severity of hemosiderin deposition and the other components of haemophilic arthropathy, the clinical score, and the number and chronicity of joint bleeds. An MRI of 41 ankle joints of 21 haemophilic boys was performed on a 3 T MRI system using an mGRE sequence in addition to the conventional protocol. Conventional MRI and mGRE were separately and independently assessed by three readers, namely, two musculoskeletal radiologists and a general radiologist for joint hemosiderin. We set as a reference the consensus reading of the two musculoskeletal radiologists, who also evaluated the presence of synovial thickening, effusion, and osteochondral changes. Excellent inter-reader agreement was obtained using the mGRE sequence compared to the conventional protocol (ICC: 0.95-0.97 versus 0.48-0.89), with superior sensitivity (90-95% versus 50-85%), specificity (95.2-100% versus 76.2-95.2%), and positive (95-100% versus 71-94.4%) and negative predictive value (91.3-95.5% versus 87-63%). Hemosiderin deposition was associated with osteochondral changes, synovial thickening, clinical score, and the total number of ankle bleeds, while it was inversely related with the time elapsed between the last joint bleed and MRI. (p < 0.05). The application of an mGRE sequence significantly improved hemosiderin detection, even when performed by the less experienced reader. Joint hemosiderin deposition was associated with the other components of haemophilic arthropathy and was mostly apparent in recent joint bleeds.

Emergency-Driven Multiple Simultaneous Invasive Procedures in Haemophilia.

Despite the controversies regarding the appropriateness and justification of simultaneous bi- and multi-concomitant surgical procedures, this operative technique is increasingly undertaken for economic reasons. This paper discusses three cases of simultaneous interventions: two involving osteoarticular procedures and one involving a complex approach encompassing general and plastic surgery. The indications in emergency-driven cases are mandatory, life-saving, and limb-saving, and not subject to debate.

Determination of body composition by dual x-ray absorptiometry in persons with haemophilia.

BACKGROUND: There is limited research on body composition in persons with haemophilia (PwH). The literature describes an increased body fat distribution and decreased lean mass in PwH compared to healthy controls using bioimpedance analysis. Using dual x-ray absorptiometry (DXA), which is known to be the most accurate method, this investigation aims to postulate reference data for body composition parameters within haemophilia severity phenotypes and age groups. METHODS: Persons underwent whole body DXA screening using Horizon. Body fat percentage, estimated visceral adipose tissue (VAT), appendicular fat and lean mass, and lean and fat mass in relation to body height were assessed. Haemophilia severity and five age groups were distinguished. RESULTS: Two hundred and one persons with mild (n = 44), moderate (n = 41), or severe (n = 116) haemophilia A/B (median age 40 [28-55; 1.IQ-3.IQ] years) were analysed. The median body fat percentage was 28.7% [25.5%-33.9%] and median estimated VAT was 657 g [403-954 g] with no significant difference between severity phenotypes (p = .474; p = .781). Persons with severe haemophilia had less lean mass compared to moderate and mild haemophilia (p = .013; p = .034). Total and appendicular fat is increased in older PwH (aged ≥40 years) compared to younger PwH (aged ≤29 years; p < .05). Lean mass did not differ between age groups. CONCLUSION: This study provides valuable reference data for body composition parameters in PwH. Persons with severe haemophilia show significantly less lean mass compared to persons with moderate or mild haemophilia. Body fat percentage and VAT did not differ between severity phenotypes, but increased with age.

Real-world effectiveness of eptacog beta in patients with haemophilia and inhibitors: A multi-institutional case series.

INTRODUCTION: The management of bleeding events (BEs) in haemophilia A (HA) and B (HB) patients with inhibitors necessitates the use of bypassing agents. The recombinant factor VIIa bypassing agent eptacog beta has demonstrated efficacy at treating BEs and managing perioperative bleeding in adults in phase three clinical studies. AIM: To provide real-world descriptions of eptacog beta use for BE treatment in patients on emicizumab or eptacog beta prophylaxis. METHODS: This is a retrospective case series of 14 patients who received eptacog beta at seven haemophilia treatment centres, with HA (n = 11) or HB (n = 3) and inhibitors or anaphylaxis to factor replacement. RESULTS: Twenty-four spontaneous and traumatic BEs are described (muscle hematomas, joint hemarthroses, port site, and epistaxis) involving 11 subjects. Eptacog beta was effective for acute bleed treatment as both first-line therapy and for treatment of BEs refractory to eptacog alfa in 23/24 events. When eptacog beta was used for prophylaxis, 2/3 patients reported a decreased frequency of breakthrough BEs compared with prophylactic eptacog alfa and one patient experienced a similar frequency of breakthrough BEs compared with prophylactic activated prothrombin complex concentrate. Eptacog beta provided effective bleed control for three subjects who underwent minor surgical procedures. Treatment with eptacog beta was estimated to be 46%-72% more cost-effective than eptacog alfa. No safety concerns or adverse events were reported. CONCLUSIONS: In this case series, eptacog beta was safe, effective, and economical as first-line therapy, treatment of refractory BEs, management of perioperative bleeding, or prophylaxis in haemophilia patients with inhibitors.

Proteomic exploration of potential blood biomarkers in haemophilic arthropathy.

Background and Aims: The pathophysiology of haemophilic arthropathy (HA) is complex and largely undefined. Proteomic analyses provide insights into the intricate mechanisms of the HA.Our study aimed to identify differentially expressed proteins in relation to the severity of HA, explore their pathophysiological roles, and evaluate their potential as HA biomarkers. Methods: Our cross-sectional observational study encompassed 30 HA patients and 15 healthy subjects. Plasma samples were pooled into three groups of 15 samples from those with severe haemophilic arthropathy (sHA), mild haemophilic arthropathy (mHA) and healthy controls. Proteomic analysis was performed using liquid chromatography-mass spectrometry. The severity of HA was assessed using the World Federation of Haemophilia Physical Examination Score and ultrasonography following the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) guidelines. Results: A total of 788 proteins were identified, with 97% of the uniquely identified proteins being expressed in all analysed groups. We identified several up and downregulated proteins across the groups that were mainly related to inflammatory and immunity-modulating processes, as well as joint degeneration. We highlighted ten proteins relevant for the development of HA: cathepsin G, endoplasmic reticulum aminopeptidase 2, S100-A9, insulin-like growth factor I, apolipoprotein (a), osteopontin, pregnancy zone protein, cartilage oligomeric matrix protein, CD44, and cadherin-related family member 2. Conclusion: Our analysis identified several proteins that shed further light on the distinctive pathogenesis of HA and could serve for biomarker research. However, these results need to be validated on a larger patient group.

Differences and similarities in patient-reported outcomes among men and women with haemophilia.

INTRODUCTION: Both men and women can be diagnosed with haemophilia and the experience with haemophilia may be different between men and women. AIM: This study aimed to compare patient-reported outcomes in men versus women with haemophilia. METHODS: This cross-sectional study is a post-hoc analysis of data collected as part of the Haemophilia-related Distress Questionnaire validation study. Adults aged ≥18 years with haemophilia A or B were recruited from one of two haemophilia treatment centres between July 2017 and December 2019. Outcomes included quality of life, measures of mental and physical health, and overall health. Unadjusted and multivariable linear regression models were used to examine potential mediators of sex-based differences in outcomes. RESULTS: Of the 139 study participants included (21 women, 118 men), the mean age was 36.9 years and most (89.2%) had haemophilia A. Approximately 85.7% and 26.3% of women and men had mild haemophilia, respectively.  PHQ-9 depression and PROMIS-29 Profile anxiety and fatigue scores were significantly higher in women than men in unadjusted and adjusted analyses. There were no statistically significant differences in other outcomes. CONCLUSIONS: Women with haemophilia are more likely to experience depression, anxiety, and fatigue than men with haemophilia. This study highlights the need for mental health services to be integrated into the care of women with haemophilia. Future research is needed to understand whether women with haemophilia are more or less likely to experience depression, anxiety, and fatigue than women without haemophilia as well as determine the impact of reduced mental health on clinical outcomes.

Clinical and Humanistic Burden of Non-inhibitor Haemophilia A in Five European Countries: Insights from the CHESS II Study.

INTRODUCTION: Haemophilia A (HA) is a congenital bleeding disorder caused by a deficiency/absence of factor VIII (FVIII) and characterised by frequent, acute and prolonged spontaneous or traumatic bleeding events, often leading to haemophilic arthropathy and progressive joint deterioration. HA severity is characterized by endogenous FVIII activity: mild (> 5-40%), moderate (1-5%), or severe (< 1%). HA poses a substantial clinical and socioeconomic burden on people with HA (PWHA), their caregivers, and society. This analysis evaluates clinical and patient-centric outcomes of a cohort of individuals with non-inhibitor HA sampled from France, Germany, Italy, Spain, and the UK in the 'Cost of Haemophilia in Europe: A Socioeconomic Survey II' (CHESS II) study. METHODS: CHESS II was a cross-sectional burden-of-illness study collecting clinical and socioeconomic data on adult (≥ 18 years) individuals with haemophilia A or B of any severity with or without inhibitors from eight European countries. Descriptive analyses were conducted examining physician-reported demographics, clinical and health resource utilisation information. PWHA-reported health-related quality of life (HRQoL) using the EQ-5D-5L and Work Productivity and Activity Impairment (WPAI) were also examined. Outcomes were stratified by HA severity and reported at country level. RESULTS: Demographics and clinical characteristics of the cohort (N = 880) were generally consistent across countries. Individuals with severe HA experienced more frequent bleeding events and joint disease despite broad use of factor replacement therapy long-term prophylaxis. A minority of those with mild or moderate HA also experienced such challenges. HRQoL and workforce participation diminished, and chronic pain increased, with increasing HA severity. CONCLUSION: This analysis provides up-to-date insights on the impact of HA across five European countries. Increasing HA severity was generally associated with worse clinical outcomes, HRQoL and workforce participation. These findings suggest a place for continued evidence-based tailored treatment and clinical management approaches in addressing the residual burden of HA.

Retroperitoneal and lower extremities muscle bleeding in acquired haemophilia A (AHA): Risk factors and implications in disability and survival.

AIM: To assess risk factors of retroperitoneal and lower extremity musculoskeletal bleed in acquired haemophilia (AHA) and perform an objective assessment of disability and influence on survival. METHODS: We included 49 patients with AHA from November 2017 to May 2023. The occurrence of any retroperitoneal or/and lower extremities bleeding manifestation was investigated. On clinical follow-up, we search for compressive femoral neuropathy and quadriceps amyotrophy. The lower extremity functional scale (LEFS) was carried out one year after the last bleeding event in all AHA patients. RESULTS: A 61.2% of patients in our AHA cohort presented with any retroperitoneal and/or lower extremities musculoskeletal manifestation. Those patients had higher percentage of major bleeding EACH2/ISTH criteria (90% vs. 57%, p = .01), needs of blood transfusions (86% vs. 57% of patients, p = .03), and haemostatic by-pass products (90% vs. 63%, p = .02). Hypertension (HR 2.6, 95% CI 1.1-5.9, p = .02), presence of autoimmune disease (HR 13, 95% CI 1.7-99, p = .01), and inhibitor level > 20 BU (HR 2.6 95% CI 1.0-6.8, p = .04) significantly predicted retroperitoneal/lower extremities clinical manifestations. Most frequent sequelae were quad atrophy (30.6%) and femoral nerve palsy (20.4%). Quad atrophy and LEFS scores under 50 were associated with increased mortality (HR 3, 95% CI 1.1-8.6 and HR 12, 95% CI 3.3-45, respectively). CONCLUSION: AHA with retroperitoneal/lower extremities bleeding involvement is of greater severity and shows high disability and worst survival outcomes. Quadriceps atrophy and LEFS scale scoring under 50 predicted mortality in our AHA patients.

Bioclinical features of haemophilia patients in Benin in 2023: Towards better care.

OBJECTIVE: To analyse the demographic, clinical and laboratory data of Beninese patients with haemophilia. METHOD: A prospective survey was conducted in three different hospitals of Benin from April 2021 to March 2022, to analyse clinical and biological features of patients with haemophilia previously diagnosed or identified based on personal/family history. RESULTS: A total of 101 patients were studied, 97 with haemophilia A and 4 with haemophilia B, including 26 new cases identified after family investigation. Their median age was 11 years, and the most frequent initial manifestations were cutaneous-mucosal haemorrhages (29.70%) and post-circumcision haemorrhages (25.74%). Previous joint bleedings were present in 77% of them, with an arthropathy in 65 cases, which particularly affected the knees (75%), elbows (41%) and ankles (29%). Factor VIII (FVIII) levels combined with activated partial thromboplastin time (APTT) values did not always enable, as would be expected, the distinction between severe and moderate haemophilia, since they were >1 IU/dl in 31 of 74 patients with APTT > 80 s, and between 1 and 2 IU/dl in 26 other cases with previous joint haemorrhages, including 18 with chronic arthropathy. Therefore, for these patients, severe haemophilia could not be excluded, and this uncertainty probably reflects technical difficulties affecting the pre-analytical and analytical stages of the APTT and FVIII/IX assays. CONCLUSION: Our study proved that haemophilia is a significant reality in Benin, but also remains under-diagnosed in some districts of the country. In addition, more reliable biological tests are needed in the future to better define the severity of the disease and improve treatment of patients.

A long term outcomes analysis of severe haemophilia A boys receiving 4 years prophylaxis on the Chinese Haemophilia Individualized escalating low dose Prophylaxis (CHIPS).

BACKGROUND: The Chinese Haemophilia Individualized Prophylaxis Study (CHIPS), which was launched in 2016, reported a significant reduction in haemarthrosis over a one-year study. However, its long-term efficacy requires verification. This paper summarizes the clinical outcomes of 18 severe haemophilia A (SHA) patients who completed one year on the CHIPS and 3 more years of follow-up. METHODS: Clinical follow-up was based on the CHIPS protocol (from July 2018 to July 2021). Escalation was based on index joint bleeding, and serial ultrasound (greyscale and colour Doppler) examinations of the index joints (both sides of the ankles, knees and elbows) were conducted every 6 months via a scoring system. RESULTS: A total of 18 SHA patients completed the 3-year study. Fifteen patients dropped out due to the financial crisis during the COVID-19 pandemic in China. The median age was 5.4 (range 4.3-6.9) years. A significant reduction in haemarthrosis was achieved, with mean annual bleeding rates reduced from 18.9 ± 2.8 to 1.7 ± 0.4 (p < 0.001), annual joint bleeding rates from 3.1 ± 0.7 to1.2 ± 0.3 (p < 0.028). 5 out of 8 target joint resolved. Sixteen doses were escalated. At study exit, the heterogeneous treatment outcomes of the SHA boys were 5 at step 4 (20-25 lU/kg, every other day), 10 at step 3 (15-20 IU/kg, 3×/week), 2 at step 2 (10-15 lU/kg, 3×/week) and 1 at step 1 (10-15 lU/kg, 2×/week). The mean FVIII consumption was 2964 IU/kg/year, with savings. The quality of life improved, with Canadian Haemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT, Chinese Version 2.0) scores ranging from 68.8 to 78.8. There was no change in the ultrasound score. CONCLUSION: Our follow-up data on the 18 SHA boys after completing one year on the CHIPS verify the long-term efficacy of the CHIPS for haemarthrosis reduction, joint health preservation, improvement in the quality of life of the boys and cost savings.

Navigating the Asia-Pacific region plasma therapies landscape: Insights from the 2023 Asia-Pacific Plasma Leaders' Network meetings.

The Asia-Pacific Plasma Leaders' Network (APPLN) plays a crucial role in addressing the regional shortage of plasma-derived medicinal products (PDMPs), particularly in low- and middle-income countries (LMICs). It provides a platform for experts to share their expertise and drive multi-stakeholder collaborations. While several PDMPs are acknowledged by the World Health Organization (WHO) as life-saving therapeutics on the Model List of Essential Medicine for treating various chronic and acute life-threatening diseases, there are still many inadequacies in the availability and affordability of PDMPs. These challenges arise from insufficient domestic supplies of plasma suitable for fractionation, as well as a lack of technical and financial capabilities to implement contract or domestic plasma fractionation programmes. At two separate dialogue forums organized by the APPLN in 2023, experts discussed the unmet needs of PDMPs for individuals living with haemophilia and immunodeficiencies in the region. They also highlighted the limited access to early diagnosis and patient-centred care in several LMICs. To address these issues, there is an urgent need to increase the availability of high-quality domestic plasma for fractionation. Adopting a stepwise approach to utilize unused recovered plasma and establishing contract fractionation programmes could be viable strategies to potentially enhance PDMP availability in LMICs. However, achieving this goal requires improving existing domestic infrastructures for blood collection, implementing adequate policy reforms and fostering competent local leadership. Ultimately, there is no 'one-size-fits-all' strategy for securing safe plasma proteins for all patients in need. Collaborative efforts are essential for achieving progressive self-sufficiency in PDMPs.

Disease and treatment burden of patients with haemophilia entering the explorer6 non-interventional study.

OBJECTIVES: We aimed to characterise baseline disease and treatment burden in a large population with haemophilia A/B, both with (HAwI/HBwI) and without (HA/HB) inhibitors. METHODS: The prospective, non-interventional explorer6 study included patients ≥12 years old with severe HA, severe/moderate HB or HAwI/HBwI of any severity, treated according to local standard of care (excluding previous/current exposure to concizumab or emicizumab). Baseline characteristics and historical clinical data were collected and patient-reported outcomes, including treatment burden, were assessed. RESULTS: The explorer6 study enrolled 231 patients with haemophilia (84 HAwI/HBwI) from 33 countries. At baseline, patients with HA/HB treated with prophylaxis had the lowest median annualised bleeding rates (ABRs; 2.0), irrespective of haemophilia type; of these patients, 27.5% (HA) and 31.4% (HB) had target joints. Patients with HAwI/HBwI treated episodically reported the highest treatment burden. Of these patients, 28.5% (HAwI) and 25.1% (HBwI) performed sports activities in the month before screening. CONCLUSION: Despite receiving routine clinical care, historical and baseline information from patients enrolled in explorer6 showed that patients with HA/HB treated episodically and patients with HAwI/HBwI had higher ABRs, higher treatment burden and participated in sports less than those with HA/HB treated with prophylaxis. Emerging treatments could be beneficial in addressing these unmet medical needs.