World Federation Of Hemophilia Research Articles

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.

Perioperative Pain Management in Hemophilic Patient Undergoing Orthopedic Surgery: A Narrative Review

Background: Hemophilia type A and B is associated with spontaneous bleeding in muscle tissues and joints. Acute hemarthrosis, representing 70–80% of all bleedings in severe hemophilia patients, is extremely painful. When surgical procedures are needed in hemophiliac patients, perioperative management should be planned with a multidisciplinary team. Our narrative review, through a rigorous analysis of the current literature, focuses on pain management in hemophiliac patients. Methods: The report synthesizes a literature review on hemophilia, adapting PRISMA guidelines. It identifies a research question on surgical procedures and perioperative pain management. Various sources, including electronic databases, are utilized. Study inclusion criteria are defined based on the research question. Forty studies are included. A detailed study selection is illustrated. Results: Guidelines for managing acute postoperative pain in the general population advocate for a multimodal analgesic administration to enhance synergistic benefits, reduce opioid requirements, and minimize side effects. Recent recommendations from the World Federation of Hemophilia (WFH) for postoperative pain management in hemophilia patients suggest tailoring treatment based on pain levels, in coordination with anesthesiologists. Conclusions: Pain management in hemophiliac patients undergoing orthopedic interventions requires a multidisciplinary approach, with further research needed to define a reliable global standard of treatment.

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

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. 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. The tool was proposed and developed by the expert working group, workshopped at conference round tables, and evaluated in two focus groups. 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. 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.

The management of liver disease in people with congenital bleeding disorders: guidance from European Association for Haemophilia and Allied Disorders, European Haemophilia Consortium, ISTH, and World Federation of Hemophilia

People with bleeding disorders (PWBD) have been exposed to the risk of developing chronic viral hepatitis and cirrhosis after replacement therapy. Today, the advent of new pharmacologic strategies for the control of hemostasis and the efficacious antiviral therapies against hepatitis C virus and hepatitis B virus have significantly reduced this risk. However, the real success for liver health in this clinical setting is based on other risk factors, such as the severity of liver disease at the time of hepatitis B virus/hepatitis C virus antiviral therapy and the exposure to highly prevalent factors of chronic liver damage (eg, metabolic dysfunction and/or alcohol) that can cause a residual risk of complications such as hepatocellular carcinoma, portal hypertension, and liver insufficiency. With this background, a group of experts selected among hepatologists, PWBD treaters, and patient representatives produced this practical multisociety guidance for the protection of liver health and the prevention and management of liver complications in PWBD based on the most updated protocols of care.

The importance and evolution of bleeding disorder registries.

Registries are excellent sources of data to address questions that are typically not evaluated in randomized clinical trials, including natural history, disease prevalence, treatment approaches and adverse events, and models of care. Global and regional registries can provide data to identify differences in outcomes and in haemophilia care between countries, economic settings, and regions, while facilitating research and data sharing. In this manuscript, we highlight five bleeding disorder registries: Country registries from Australia and China, Paediatric Network on Haemophilia Management (PedNet) data on children who have received emicizumab, data from the European Haemophilia Safety Surveillance (EUHASS) system, and data on women and girls with haemophilia from the World Federation of Haemophilia (WFH) registries. Data from these and other bleeding disorder registries have been and will continue to be used to advance patient care, understand treatment patterns and adverse reactions, and identify areas of increased need and focus.

Riding the wave of change: Providing solid ground to support nursing with patient transitions to novel haemophilia therapies.

Haemophilia nursing practice has experienced a shift in the past decade, as the historic chief focus on factor infusions shifted to extended half-life products, bispecific antibody therapies and other non-replacement therapies. This evolution has driven a need for changes in nursing practice in many haemophilia treatment centres. This article intends to provide insights to the haemophilia nurse to champion practice changes at their haemophilia treatment centres. Two popular change theories, Lewin's three-step change model and Kotter's eight-step change model are discussed as a framework for haemophilia nurses to think, structure and be leaders in change. Examples of these models in practice could give guidance and examples to reflect on for haemophilia nurses needing to make changes in their practice settings. These models of change, alongside existing haemophilia nurse competencies and tools such as the shared decision-making tool from the World Federation of Hemophilia, can assist the nurse to be a capable change agent to usher in these new innovations.

Prevalence of Hemophilia and Clinicodemographic Characteristics of Hemophilic Patients Aged ≤ 18 Years in Thi-Qar, Iraq.

Objectives. This study aims to determine the prevalence of hemophilia in Thi-Qar, Iraq and study clinical and demographic characteristics of patients with hemophilia. Methods. In this cross-sectional study, data were obtained by reviewing all patient medical records and interviewed with the patients and their parents in 2022. The total number of patients enrolled for this study was 110 children. Results. The prevalence of hemophilia in Thi-Qar was 9.5/100 000 population (18.7/100 000 males). Factor VIII inhibitors were positive in 13.1% of patients with hemophilia A (HA). Target joints were developed among 41.4% and 27.3% of patients with HA and hemophilia B, respectively. Hepatitis C virus was positive in 3% of those with HA. Inhibitors development and arthropathy were more among those with severe disease (22% and 46.3%, respectively). Conclusion. Hemophilia prevalence in Thi-Qar was higher than the total prevalence in Iraq reported by World Federation of Hemophilia in 2022.

Factor First: An Assessment of Emergency Department Care of Patients with Hemophilia

Background: With the establishment of hemophilia treatment centres (HTCs) and home infusion programs for factor replacement therapy, emergency department use among patients with hemophilia occurs less frequently, with patients often presenting for significant bleeding events only. As a result, the management of patients with hemophilia can represent a challenge to emergency department (ED) physicians and staff. Both delays in diagnosis of a bleeding event, and timely administration of hemostatic therapy have been associated with patient morbidity and mortality. The World Federation of Hemophilia, in addition to other organizations, emphasize the importance of timely receipt of clotting factor replacement therapy, providing treatment at the time a bleed is suspected. If a patient with hemophilia is registered with a HTC, they often carry a wallet card, or have a formalized treatment plan, outlining their diagnosis and emergency treatment of bleeding recommendations to ensure timely access to hemostatic therapy. The aim of this study was to describe ED management of patients with hemophilia at a single Canadian HTC, with a focus on use of individualized emergency bleeding management protocols, and time to receipt of hemostatic therapy within the ED. Methods: Adult patients with hemophilia A or B (FVIII or FIX ≤40%), of any severity, followed at the Southern Alberta Rare Blood and Bleeding Disorders Comprehensive Care Program, were identified for inclusion. ED health utilization and ED encounter management data for each of the four hospital sites in Calgary, AB was obtained from the electronic health record for the cohort, through to 2022. Results: A total of 191 patients with hemophilia A and B were identified for study inclusion. 153 patients with hemophilia A (mild 64.7%; moderate 5.9%; severe 28.8%) and 38 patients with hemophilia B (mild 44.7%; moderate 36.8%; severe 18.4%). Males comprised 77.5% of the patient cohort. A total of 393 ED visits occurred over the study period. Less than a third of ED visits were associated with receipt of hemostatic therapy (either desmopressin or clotting factor concentrate). The median time from triage to ordering of hemostatic therapy was 2.9 hrs (IQR 2.3-3.2), and median time from triage to administration of hemostatic therapy was 4.2 hrs (IQR 3.1-4.2). For ED visits due to suspected bleeds, the proportion of patients who received either coagulation factor replacement or desmopressin within two hours of ED triage is depicted in Figure 1. Time to receipt of hemostatic therapy did not significantly differ whether desmopressin or clotting factor concentrate was administered. The number of ED visits in which the individualized emergency bleeding management protocol was accessed is depicted in Figure 2. Among those accessed in 2022, the proportion of protocols that were updated within the last 365 days was 86.8%. Less than 20% of ED visits were associated with a hematology consultation. Conclusions: Increasing utilization of individualized emergency bleeding management protocols for patients with hemophilia was observed; however, significant delays in timely receipt of hemostatic therapy remains, with infrequent involvement of hematology in consultation. Time to receipt of potentially life-saving hemostatic therapy for our cohort falls outside of hemophilia care standards. This data provides a better understanding of the experience of patients with hemophilia in the ED and provides an opportunity to define further quality improvement interventions to ensure quality care metrics in this population are met.

Emicizumab Efficacy in Severe Hemophilia (A): Experience in Ecuador

Introduction: In Ecuador, there are 1708 cases of hemophilia in a population of 17,643,060 habitants; according to the World Federation of Hemophilia (WFH) Annual Global Survey Report 2020 released in October 2021. Eleven patients use emicizumab in Ecuador (ten patients under ministerial authorization, and one patient through private insurance); being the first administered in June 2021. Objectives: To describe the demographic characteristics of patients receiving emicizumab in Ecuador. To determine efficacy and response with emicizumab: based on annual bleeding rate (ABR), performance status assessment, activity, and participation. Methods: Population: Pediatric Severe Hemophilia A (PwHA) patients (<12 years) and adults/adolescents (>12 years), both from the public and private health sector. Study design: Retrospective, multicentric study, with a case-report research design. The sources of information were the medical records of the patients. Efficacy variables: ABR was calculated by: (number of bleeds/number of days times 365.25). Body structure and function was assessed with the Hemophilia Joint Health Score 2.1 (HJHS). Activity and participation were assessed with the Functional Independence Score in Hemophilia (FISH). Statistic analysis: Shapiro-Wilk test to know the distribution of the sample, t-Test paired tests (parametric), Wilcoxon statistic (non-parametric); Descriptive statistics: relative frequencies, measures of central tendency and dispersion, column graphs. Analysis and results: Ten patients with an average (Q1,Q3) age of 11.5 years (7.15) were registered. The youngest patient was one year old and the oldest, fifty years old. 90% (n:9) had hemophilia A with high-response inhibitors. Prior to starting emicizumab: 20% (n:2) presented Central Nervous System bleeding, 30% (n:3) had muscle bleeding, and 10% (n:1) developed catheter-associated infection. The mean ABR was 10 pre-emicizumab events, and 0.3 post-emicizumab events (p=0.002), with follow-ups at 22 months (n: 2), 17 months (n:2), 3 months (n:2 ), 4 months (n: 3), 5 months (n: 1). The mean HJHS (±SD, n) was 20.9 (± 20,096, 10) pre-emicizumab, and 9.7 (± 16.52, 10) (p=0.003) The mean by FISH (±SD, n) was 16.2 (± 8.59, 10) pre-emicizumab, and from 22.6 (± 11.62, 10) with the use of emicizumab. The use of the t-Test for paired samples determined that there are statistically significant differences between the pre-emicizumab and post-emicizumab groups for the variables ABR, HJHS and FISH (95% confidence level). Conclusion: The use of Emicizumab allowed better control of joint bleeding; and it contributed favorably in the evolutionary course of both the functional state and the activity. It is essential to corroborate these results with a longer follow-up and a larger sample size. Bibliography: 1. Alvarez Roman M: Spanish guidelines for the management of hemophilia. 2022, 1-190. 2. Callaghan M, Negrier C, Paz-Priel I, Chang T, Chebon S y col: Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies. Blood. 2021;137(16):2231-2242 3. Carcao M, Escurriola C, Santagostina E, Oldenburg J, Liesner R y col: The changing face of immune tolerance induction in haemophilia A with the advent of emicizumab. Haemophilia. 2019;25:676-684. 4. Ellsworth P, Ma A: Factor-mimetic and rebalancing therapies in hemophilia A and B: the end of factor concentrates?. Hematology Am Soc Hematol Educ Program. 2021, Dec 10;2021(1):219-225. 5. Young G: Management of children with hemophilia A: How emicizumab has changed the landscape. Journal of Thrombosis and Haemostasis. 2021 Jul;19(7):1629-1637

Overcoming Hurdles in Hemophilia Care: The Impact of World Federation of Hemophilia Humanitarian Aid on Arthroplasties and Orthopedic Surgeries in Low-Middle-Income Setting

Introduction: Hemophilia is a hereditary bleeding disorder characterized by the absence or deficiency of clotting factors, leading to prolonged bleeding and joint damage. In lower-middle-income countries (LMICs) like India, access to standard care for hemophilia has been limited, resulting in many children not receiving prophylaxis and developing severe joint disease in young adulthood. This significantly impacts their quality of life and productivity. Arthroplasty has offered hope for hemophiliacs with established joint disease, but its accessibility in LMICs faces numerous hurdles, including lack of laboratory diagnostics and monitoring facilities, shortage of hematologists, absence of advanced orthopedic surgical teams, limited insurance coverage, and inadequate access to clotting factor concentrates (CFCs) to support surgeries. Comprehensive care centers can address some challenges, but the availability of CFCs remains crucial for effective corrective arthroplasties and other orthopedic surgeries. Aim: This retrospective analysis aims to assess the impact of the World Federation of Hemophilia (WFH) humanitarian aid in facilitating effective corrective arthroplasties and other orthopedic surgeries at a comprehensive care center in a lower-middle-income country. Methods: The study was conducted at a comprehensive care center in India that previously lacked access to CFCs until the initiation of WFH humanitarian aid. Clinical data of patients with hemophilia who underwent major orthopedic surgeries and received CFC support from WFH humanitarian aid between November 2017 and June 2023 were reviewed. Patients with inhibitor-positive status were excluded. Patients were assessed in a comprehensive clinic prior to the elective arthroplasty. The analysis evaluated the utilization of CFCs in orthopedic surgeries, immediate surgical outcomes, and the effect of regulating CFC dose guided by lab monitoring. Additionally, the study audited the impact on CFC utilization when performing two surgeries in one sitting. Data analysis was performed using SPSS version 20.Continuous variables are depicted as mean±SD or median with range. Percentages represent categorical variables. Results: The study included 21 patients with Hemophilia {19 Hemophilia A(90%) and 2 Hemophilia B(10%)} who underwent orthopedic surgeries with CFC support from WFH humanitarian aid.There were 18(85%) patients with severe Hemophilia.Elective arthroplasty was done in 17 patients (81%) and 4 patients(19%) underwent emergency internal fixation. The median age of patients who underwent surgery was 31(range 18-75) years. Elective unilateral knee arthroplasty was done in 7(33%)patients, hip arthroplasty in 2(10%)patients and elbow arthroplasty in 1(5%)patient.Bilateral knee arthroplasty was done in a single surgical setting for efficient CFC utilization in 7 (33%) patients. Extended Half-life (EHL)CFC was used in 10 patients (48%), Standard half-life (SHL) CFC in 2 patients (10%), while the others received a combination of both. Mean use of CFC was 410(Range 270-767) units/kg in Hemophilia A and 650(range 500-800)units/kg in Hemophilia B. The mean EHL FVIII utilization in Bilateral TKR was 400 (Range 322-536) units/kg. None of the patients experienced major intraoperative bleeding or post-operative thromboembolism.No patient developed inhibitor positivity when tested post operatively. Notably, CFC utilization in all patients was found to be less than the empirically recommended levels in WFH guidelines for resource-constrained settings. Table 1 demonstrates the demographics, Type of surgery, CFCs used and immediate outcomes of orthopaedic surgeries done using WFH Humanitarian Aid. Conclusion: The findings of this retrospective analysis demonstrate the transformative impact of WFH humanitarian aid in a comprehensive care center for hemophiliacs in a lower-middle-income country. With access to CFCs, effective corrective arthroplasties and orthopedic surgeries were made possible, providing hope and improved quality of life for patients with established joint disease. The study underscores the vital role of WFH humanitarian aid in enhancing care outcomes for hemophiliacs in resource-limited settings and emphasizes the need for continued support and collaboration to advance hemophilia care globally.

PB1254 A New Tool to Assist in Treatment Selection - The World Federation of Hemophilia (WFH) Shared Decision-Making (SDM) Tool

PB1254 A New Tool to Assist in Treatment Selection - The World Federation of Hemophilia (WFH) Shared Decision-Making (SDM) Tool

Bridging the gap: Survey highlights challenges and solutions in outreach and identification of people with inherited bleeding disorders.

Inherited bleeding disorders (IBD) are genetic conditions that affect blood clotting, leading to complications such as prolonged or spontaneous bleeding into muscles or joints. Early identification and treatment are crucial to prevent complications and improve outcomes. However, effective patient outreach and identification programs for IBD face significant challenges globally. This study aimed to identify successful patient outreach initiatives for IBD, barriers encountered during implementation, and approaches used to overcome them. The World Federation of Haemophilia (WFH) conducted a survey of its national member organizations and other patient associations, totalling 153 organizations, to identify common strategies, barriers to their implementation, and solutions for outreach and the identification of people with IBD. The survey consisted of both closed-ended and open-ended questions, and the data were analysed using descriptive statistics and thematic analysis. Common challenges included resource and sustainability-related aspects such as financial constraints, limited lab equipment for diagnosis, and inadequate government commitment. Significant barriers also encompassed physical/geographical challenges like difficulty accessing remote areas, and inadequate logistical support and transportation. Seven themes emerged to enhance patient outreach: resource mobilization; awareness-raising and advocacy; knowledge and capacity building; collaboration and partnership; decentralization of services; improved logistical support and infrastructure; utilization of technology and innovation; and financial aid and incentives. Multistakeholder collaboration, coupled with secured government commitment, is crucial for improving global outreach, diagnosis rates, and access to care for individuals with IBD. Customized outreach programs should consider regional contexts, financial constraints, and prioritize innovation.

Von Willebrand Disease: Gaining a global perspective.

Recent guidelines for von Willebrand Disease (VWD) highlighted the challenges in diagnosis and management. Identifying the number of persons with VWD (PwVWD) internationally will help target support to aid diagnosis of PwVWD. To examine international registration rates of PwVWD, the influence of income status, geographical region and the age and sex profile. Cumulatively, these data will be used to inform future strategy from the World Federation of Haemophilia (WFH) to address unmet clinical and research needs. Data from the 2018/2019 WFH Annual Global Survey (AGS) were analysed, providing a global perspective on VWD registration. Registration rates are lowest in South Asia (0.6/million population) and highest in Europe/Central Asia (50.9/million population, 0.005%), but below the expected prevalence rate (0.1%). National economic status impacted VWD registration rates, reflecting variation in access to optimal healthcare infrastructure. Females represented the majority of PwVWD globally, however, in low-income countries (LIC) males predominated. Age profile varied, with markedly higher rates of paediatric registrations in North America, Middle East and North Africa and South Asia. Rates of type 3 VWD registrations were significantly influenced by economic status (81% of VWD diagnoses in LIC), suggesting only the most severe VWD types are diagnosed in resource limited settings. Significant variation in registration rates of PwVWD exist internationally and is influenced by income status and the presence of HTC networks. Improved understanding of registration rates will enable targeting of advocacy to improve awareness, diagnosis and support for PwVWD internationally. Registration rates of People with Von Willebrand Disease (PwVWD) vary internationally and are influenced by national income status Although females represent the majority of PwVWD globally, in low income countries (LIC) males predominated, possibly related to stigma surrounding gynaecological bleeding. Rates of type 3 VWD registration were significantly influenced by economic status (81% of VWD diagnoses in LIC), suggesting only the most severe VWD types are diagnosed in resource limited settings.

Commentary on Laffan et al expert consensus for equitable care for VWD.

In a recent issue of Haemophilia, Laffan et al. report ‘An expert consensus to define how higher standards of equitable care for von Willebrand disease can be achieved in the United Kingdom and Republic of Ireland.’’1 This project aimed to generate recommendations to improve equitable access to care for VWD patients. A modified Delphi approach was used and clear criteria for stopping and consensus were defined. Ultimately, eight recommendations were derived and include four that specifically address standardised and improved history taking about bleeding events, especially heavy menstrual bleeding, as well as additional recommendations focused on care delivery, better evidence for prophylaxis, and equity in terms of time to diagnosis and quality of life assessments. The expert authors are to be applauded for this effort and their focus on gender bias in the bleeding disorder community. A few points raised by this study merit additional discussion. The health care providers included were predominantly Haematologists, with Nurse Specialists as the second most common group; only one Obstetrician was included. Most respondents were from England and Ireland. Notably, a very high level of consensus was achieved after only one round of voting, which while reassuring, is not surprising given the relative homogeneity of the group. VWD patients interact with many parts of the health care system, and as a community, we need to turn our focus outward to other providers if we intend to truly improve the time to diagnosis and care. We also need to consider the specific challenges facing those living in low and middle-income countries, as the solutions must be tailored to the available resources and cultural settings. Certainly, the foundation of change needs to involve rejecting sexist attitudes towards individuals with bleeding disorders and valuing the lived experiences of patients. Along those lines, the patient voice must be included in future efforts directed at improving equitable access to care. We need to listen to patients and patient organizations to understand their priorities and tailor our approaches appropriately. Failure to do so could perpetuate the current state of inequity, no matter how well-meaning the intentions. As an example, the ongoing focus of many national and international organizations on hemophilia (as evidenced by the very names of these organisations) creates a barrier for VWD patients and healthcare providers. Women have been telling us for years that they feel poorly represented within Hemophilia Treatment Centres and by Hemophilia-focused patient organisations.2-4 It is time we listen and act. Of note, the recommendation with the lowest consensus at 80% was ‘Patients should always be involved in treatment options for their VWD’—clearly, there is work left to do to truly achieve patient-centred care. The authors include a detailed discussion of the barriers to care, which are many, especially at the primary care level. Engaging with primary care practitioners (PCP), who are often the first point of contact for someone with bleeding symptoms, seems an additional critical step in creating a functional and integrated system to diagnose and manage these patients. The value of multi-disciplinary clinics has been recognised, but in contrast to these being specialist centred, the inclusion of PCP in these models of care could be considered. Lastly, as highlighted by the authors, the quality of evidence for critical aspects of the care of VWD patients, such as prophylaxis, is poor. Although there are many barriers to performing these studies including the multiple types and subtypes of VWD as well as the numerous bleeding symptoms experienced by patients, the need for high-quality evidence is clear. In the recently published ASH (American Society of Hematology) ISTH (International Society on Thrombosis and Hemostasis) NHF (National Hemophilia Foundation) WFH (World Federation of Hemophilia) VWD Management Guidelines, all 12 recommendations were conditional, due to the lack of high-quality evidence.5 Laffan et al. appropriately identify the need for future studies to further develop the evidence base on which we base management decisions for VWD patients. Paula James receives research funding from Bayer and consultancy fees from Band/Guardian Therapeutics and Star/Vega Therapeutics. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Haemophilia item bank based on International Classification of Functioning, Disability and Health: a systematic review

ABSTRACTBackground and ObjectivesHaemophilia comprises a continuum of blood disorders that often include joint and muscular dysfunction, which may lead to a constellation of activity limitations and participation restrictions. However, there is scant research incorporating functional assessment scales into the common language provided by the International Classification of Functioning, Disability and Health (ICF). This study aims to identify the ICF categories to include in an item bank of functioning aspects relevant for haemophilia.Design and MethodsA systematic search was carried out in July 2021 based on the PubMed MEDLINE, CLINICAL, and Cochrane databases for qualified articles, investigating haemophilia-specific scales and the scales recommended by the World Federation of Haemophilia (WFH) linked to ICF categories between 2001 and 2021. Well-trained healthcare professionals in the haemophilia field and ICF evaluation conducted group discussions to determine the ICF items for haemophilia.ResultsA total of 112 out of 176 items measuring function were collected for the haemophilia ICF item bank, including 32 items for body function (b), 45 items for activity and participation (d), 27 items for environmental factors (e), and 8 items for body structure(s).Interpretation and ConclusionsWe recommend that future haemophilia research use the haemophilia-specific ICF item bank, which could capture a whole spectrum of functional measurements and facilitate multidisciplinary and worldwide communication. This study also indicates that further development and analysis of the psychometric properties of the 112 haemophilia-related ICF items is warranted.

Pain assessment and management in the Moroccan haemophilia population: a prospective descriptive study

Abstract Introduction For people with haemophilia (PwH) who live in developing countries, haemophilia continues to be a condition with serious medical and social consequences. In Morocco, the efforts of patient associations and medical teams have led to the creation of a national programme for haemophilia care since the end of 2012, and the country is no longer solely reliant on World Federation of Hemophilia (WFH) donations for access to factor products. There is growing recognition of the impact of the pain experienced by PwH. To continue to improve treatment for PwH in Morocco, it is important to ensure that they are also able to manage haemophilia-related pain. Aims This study aims to describe the prevalence, characteristics, and effects of pain experienced by PwH in Morocco for the first time, in order to increase understanding, and to support consideration of interventions and improvements in care. Methods We conducted a prospective, descriptive survey of the experience of pain in PwH attending the Department of Clinical Hematology and Pediatric Oncology in Casablanca, using the Multidimensional Hemophilia Pain Questionnaire (MHQP) approved by the WFH. All PwH with mild, moderate or severe haemophilia and over 18 years of age who presented to the department during the study period were included; consent was obtained. The data collection period lasted 6 months from October 2020 to April 2021. Results 60 PwH completed the questionnaire (51 haemophilia A, 9 haemophilia B; 38 severe, 22 moderate). All respondents had experienced pain, 90% during the previous year and 75% during the last 3 months. 60% reported the occurrence of pain more than once a week. 65% reported that the right knee was the most painful site in the past year, followed by the right ankle (58%). The right knee was also the site of pain with the most negative impact in the past year. 58% responded that the evening was the time of most intense pain. The therapeutic strategies used against pain were pharmacological and non-pharmacological. 60% of respondents reported using analgesics and 50% reported using coagulation factor substitution for pain relief. Regarding non-pharmacological strategies, rest was reported by 40%, elevation of the painful site/change of position by 20%, and ice by 10%. The majority reported being satisfied or very satisfied with the current treatment of their pain by health professionals. Conclusion This study shows that pain is still very present in PwH treated at our haemophilia centre, with a significant impact on different areas of life. There is a need for action to standardise treatment approaches and develop protocols for pain management in PwH.

Factors associated with delays in seeking treatment for acute bleeding among persons living with haemophilia in Uganda: a cross-sectional mixed methods study

Abstract Introduction Haemophilia is associated with a high tendency of acute bleeding episodes which can lead to severe morbidity and mortality in the absence of prompt care. Although delay in seeking care can lead to adverse outcomes, many people with haemophilia (PwH) in Uganda do not report to haemophilia treatment centres (HTCs) for treatment in the event of acute bleeding within the two hours recommended by the World Federation of Hemophilia (WFH). Information on factors associated with delays in seeking care is limited. A study among people with haemophilia presenting at five regional treatment centres across Uganda found transport costs is a major issue impacting treatment seeking for acute bleeds Aims This study aims to determine the extent and factors associated with delays in seeking treatment for acute bleeding among people with haemophilia (PwH) in Uganda to inform appropriate mitigating stratregies and hence improve health outcomes and quality and life. Methods The study was conducted in five haemophilia treatment centres (HTCs) across Uganda and used a cross-sectional design with mixed methods of data collection. PwH seeking care at the HTCs for acute bleeding episodes were consecutively sampled. A pre-tested questionnaire was used to collect data. Alongside this, qualitative interviews explored health workers’ perceptions of factors associated with delays in seeking treatment among patients. Health workers were purposively selected. The quantitative data were analysed using STATA version 16; qualitative data were analysed manually using inductive thematic analysis to generate codes, categories, sub-themes and themes. Multivariate modified Poisson regression analysis was used to determine factors associated with delay to seeking treatment at HTCs. Results 224 male PwH, aged 1 to 67 years (median 11 years) were included in the analysis. The time taken following an acute bleeding symptom to attending the HTC ranged between 1 and 65 hours, with a median of 9 hours. PwH were more likely to delay seeking treatment for acute bleeding episodes if they used public means of transport to the HTC (aPR 1.39; 95% CI 1.22-1.59). PwH who took immediate other actions on recognition of a sign of an acute bleeding episode were less likely to delay seeking treatment at the HTC (aPR 0.75; 95% CI 0.66-0.84). Conclusion Delays in seeking treatment among PwH in Uganda are the result of an interplay between individual and health system factors. Continued information and education programmes are needed to ensure PwH and caregivers understand the benefits of early treatment-seeking, alongside expanding HCP knowledge and capacity building. Mobile clinics and home therapy could reduce travel and waiting times for those needing to access treatment. Addressing these issues could help to provide a level of care for PwH that helps to ensure improved quality of life and better health outcomes.

Genotype Hemophilia Screening Program Identified 2 Novel Variants Including a Novel Variant (c.5816-2A > G) Causing a Pathogenic Variant of the Factor 8 Gene.

Establishing a national screening program for hemophilia patients is highly encouraged by the World Health Organization and the World Federation of Hemophilia. Hence, this study aimed to analyze the variant spectrum of F8 and F9 genes in Arab hemophilia patients. Molecular genetic and sequencing studies were performed on a cohort of 135 Saudi hemophilia patients. Out of all screened hemophilia patients (97 hemophilia A and 39 hemophilia B), 15 (11.1%) were positive for inversion 22 and 4 (3%) for inversion 1. Out of a total of 32 (23.7%) substitution/deletion mutations, 2 novel variants were identified: a novel splice acceptor site missense mutation (c.5816-2A > G) causing a pathogenic variant of the F8 gene and another splicing site point mutation in intron/exon 23 (g.164496G > A). The frequent F8 variants were (c.409A > C, p.T137P) in exon 4, (c.760A > G) in exon 6, and (c.1835G > C, p.R612P) in exon 12, while the frequent F9 variants were (c.580A > G) in exon 6 and (c.880C > T) in exon 8. These study data will enrich the spectrum of the genetic databases in the Arab population that could be applied in the future for national genetic counseling.

Usefulness of Emicizumab Associated with Immune Tolerance Induction in Patient with Hemophilia a and Inhibitors: Experience in Cuenca-Ecuador

Background: Referring to the World Federation of Hemophilia (WFH) 2020 Annual Global Survey Report published in October 2021: In Ecuador, with a population of 17,643,060 inhabitants, there are 1,708 cases of hemophilia, 99 cases of Von Willebrand disease, and 7 cases of other coagulation disorders. Within the hemophilia A group, 21 patients have active inhibitors, and there is a record of 2 new cases of inhibitors in relation to the previous notification. Emicizumab is a bispecific, humanized monoclonal antibody that binds activated FIX and factor X (FX) resulting in the generation of activated FX (FXa) which then catalyzes the formation of thrombin from prothrombin. Based on the HAVEN 1-4 clinical trials, the FDA and EMA approved the use of Emicizumab as prophylaxis in Hemophilia A (with and without inhibitors) in both adults/adolescents (>12 years) and pediatrics (<12 years). In both the primary analyzes and long-term follow-up, emicizumab produced statistically and clinically significant reductions in annual bleeding rates compared with Factor VIII prophylaxis (in patients without inhibitors); and with bypassing agents (in patients with inhibitors). These trials excluded patients in immune tolerance (ITI). Keywords: emicizumab, immune tolerance, hemophilia. Objectives: -Assess the usefulness of Emicizumab in immune tolerance in terms of bleeding control, osteoarticular health and functional activity Materials and Methods: 1) The evaluation was carried out in a 9-year-old patient (boy) with severe Hemophilia A and high titer inhibitors who, prior to the start of ITI, had predictive factors of high risk and poor prognosis (historical peak 234 UB, 5 years since inhibitor screening) with 4-8 joint bleeds per year. The ITI scheme used was with plasmatic Factor VIII 100 IU/Kg 3 times a week with management with bypass agents on demand (ITI duration: 3 years) and inclusion of emicizumab 2 years after starting the strategy 2) The analysis was determined based on periodic clinical evaluations, osteoarticular status was assessed through the Hemophilia Joint Health Score 2.1 (HJHS), Disease Activity Score (DAS28); and functional activity through Functional Independence Score in Hemophilia (FISH), and Health Assessment Questionnaire (HAQ). An analysis was made prior to the start of immune tolerance and after reaching immunological tolerance. Results: 1) This strategy contributed to better control of joint bleeding, and therefore to the inhibitor eradication process. 2) Improved the evolutionary course of his osteoarticular state: - Prior to ITI: DAS28: 4.26 (moderate activity), HJHS 33. Target joints: left knee and ankle. - After immunological tolerance: DAS28: 1.87 (clinical remission), HJHS 12. 3) Favorable progression of his functional status, despite slight limitation of his left knee in flexion (sequel to recurrent episodes of hemarthrosis): - Prior to the start of ITI: FISH 14, HAQ: 1.50 (severely affected functional capacity), functional scale IV (use of a wheelchair). - After immunological tolerance: FISH 27, HAQ: 1.00, functional scale II (able to carry out activities of daily living with slight difficulty). Conclusions: 1) Larger-scale studies and accumulated evidence are needed that allow us to establish the usefulness of Emicizumab in ITI and therefore corroborate these results. 2) We must establish the best clinical application profile and the economic impact of these therapies; especially in health systems like ours, in which accessibility to drugs is complex and optimization of resources is the norm. Bibliography: 1. Alvarez Roman M: Guías Españolas para el manejo de la hemophilia. 2022, 1-190. 2. Callaghan M, Negrier C, Paz-Priel I, Chang T, Chebon S y col: Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies. 2021;137(16):2231-2242 3. Carcao M, Escurriola C, Santagostina E, Oldenburg J, Liesner R y col: The changing face of immune tolerance induction 3. Hematology Am Soc Hematol Educ Program. 2021, Dec 10;2021(1):219-225. 4. Young G: Management of children with hemophilia A: How emicizumab has changed the landscape. Journal of Thrombosis and Haemostasis. 2021 Jul;19(7):1629-1637 Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Global epidemiology of factor XI deficiency: A targeted review of the literature and foundation reports.

Hereditary factor XI (FXI) deficiency is a rare coagulation disorder that may result in excessive bleeding requiring intervention to restore haemostasis. The aim of this review was to report the current knowledge of the worldwide incidence and prevalence of FXI deficiency. A targeted PubMed search using terms related to FXI deficiency was conducted to identify studies published from April 2002 through April 2022. A manual search supplemented the electronic search. Studies were eligible for data abstraction if they reported population-based incidence proportions/rates or prevalence proportions for FXI deficiency. The electronic and manual searches returned 253 publications. After applying exclusion criteria, seven publications were included in the analysis, including a global report from the World Federation of Haemophilia (WFH). Six publications provided information on the prevalence of FXI deficiency that included 74 countries and regions. The estimated prevalence of FXI in the WFH report ranged from 0/100,000 in several countries to 55.85/100,000 individuals in the United Kingdom. Prevalence estimates in the PubMed findings ranged from .1 to 246.2/1,000,000 inhabitants with varying methods of case identification and time periods of analysis. One study estimated the incidence of FXI deficiency in Yecla, Spain at 2% of blood donors and .09% of hospital inpatients/outpatients with activated partial thromboplastin time (aPTT) tests. FXI deficiency is rare across the world, but additional steps could be taken to improve incidence and prevalence estimation, for example, development of a consistent FXI deficiency definition and incorporating genetic testing into a clinical routine to better identify and characterise cases.