Persons With Haemophilia Research Articles

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

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. 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. 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 657g [403-954g] 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 ≥40years) compared to younger PwH (aged ≤29years; p<.05). Lean mass did not differ between age groups. 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.

Proactive systematic hemophilia carrier screening: a step toward gender equity in hemophilia care

AbstractDespite numerous efforts to raise awareness, many hemophilia carriers and female persons with hemophilia (PWHs) remain undiagnosed. Between May 2021 and April 2023, we identified potential and obligate carriers of hemophilia A (HA) and hemophilia B (HB) by updating pedigrees of all PWHs followed at the Cliniques universitaires Saint-Luc, Brussels. Retrospective data on previously screened females were collected, including bleeding history, coagulation factor levels, and testing for the proband’s pathogenic variant. In addition, a proactive approach involved sending 125 invitation letters to unscreened or incompletely screened individuals, through related PWHs. In pedigrees of 287 male PWHs (226 HA and 61 HB) and 7 female index patients from 236 families (184 HA and 52 HB), a total of 900 female individuals were identified. Of those, 454 were obligate and/or genetically proven carriers, and 118 were noncarriers. Genetic testing was conducted in 133 obligate, 237 potential, and 4 sporadic carriers, with 190 obligate and 328 potential carriers remaining untested. Among carriers with known factor levels (261/454), 42 HA (23.0%) and 23 HB carriers (29.5%) had a factor level <40 IU/dL. Carriers with a factor deficiency were screened on average 6 years earlier than other females (P = .034). This study, to our knowledge, represents the first systematic effort to identify potential carriers among families of all PWHs within a single center, emphasizing the challenges in comprehensive screening for female individuals genetically linked to one or more PWHs. Such initiatives are vital for achieving equitable access to hemophilia care for all potentially affected individuals, irrespective of gender. This trial was registered at www.ClinicalTrials.gov as #NCT05217992.

Application of Artificial Intelligence and Machine Learning Was Not Able to Reliably Predict Poor Outcomes in People With Hemophilia.

Background Artificial intelligence (AI) and machine learning (ML) are currently used in the clinical field to improve the outcome predictions on disease diagnosis and prognosis. However, to date, few AI/ML applications have been reported in rare diseases, such as hemophilia. In this study, taking advantage of the ATHNdataset, an extensive repository of hemostasis and thrombosis data, we aimed to demonstrate the application of AI/ML approaches to build predictive models to identify persons with hemophilia (PwH) who are at risk of poor outcome and to inform providers in clinical decision-making towards helping patients prevent long-term complications. Materials and methods This project was carried out in two steps. First, the data were mined from ATHN 7, a subset study of the ATHNdataset, to determine markers that defined "poor outcome." Second, we applied multiple AI/ML approaches on the ATHNdataset to validate our findings and to develop predictive models to identify PwH at risk of poor outcomes. The classical regression-based predictive model was used as a reference to evaluate the performance of various AI/ML models. Results Our models included features similarly distributed to response variables of interest, resulting in a limited ability to distinguish poor outcomes. Low recall (<53%) resulted in no single model reliably predicting poor outcomes out of all actual positive cases. Our results suggest that, to build a more useful AI/ML model, we may need a larger dataset size along with additional features. Furthermore, our results showed that most of the AI/ML models outperformed the classical logistic regression model in both model accuracy and precision. Conclusions Our AI and ML model showed limited ability to predict poor outcomes in people with hemophilia.

Reconstruction of the historic time course of blood-borne virus contamination of clotting factor concentrates, 1974-1992.

Factor VIII and IX clotting factor concentrates manufactured from pooled plasma have been identified as potent sources of virus infection in persons with hemophilia (PWHs) in the 1970s and 1980s. To investigate the range and diversity of viruses over this period, we analysed 24 clotting factor concentrates for several blood-borne viruses. Nucleic acid was extracted from 14 commercially produced clotting factors and 10 from nonremunerated donors, preserved in lyophilized form (expiry dates: 1974-1992). Clotting factors were tested by commercial and in-house quantitative PCRs for blood-borne viruses hepatitis A, B, C and E viruses (HAV, HBV, HCV, HEV), HIV- types 1/2, parvoviruses B19V and PARV4, and human pegiviruses types 1 and 2 (HPgV-1,-2). HCV and HPgV-1 were the most frequently detected viruses (both 14/24 tested) primarily in commercial clotting factors, with frequently extremely high viral loads in the late 1970s-1985 and a diverse range of HCV genotypes. Detection frequencies sharply declined following introduction of virus inactivation. HIV-1, HBV, and HAV were less frequently detected (3/24, 1/24, and 1/24 respectively); none were positive for HEV. Contrastingly, B19V and PARV4 were detected throughout the study period, even after introduction of dry heat treatment, consistent with ongoing documented transmission to PWHs into the early 1990s. While hemophilia treatment is now largely based on recombinant factor VIII/IX in the UK and elsewhere, the comprehensive screen of historical plasma-derived clotting factors reveals extensive exposure of PWHs to blood-borne viruses throughout 1970s-early 1990s, and the epidemiological and manufacturing parameters that influenced clotting factor contamination.

Humanistic burden of haemophilia A without inhibitors: A cross-sectional analysis of the HemoLIFE study.

To evaluate the impact of haemophilia A without inhibitors on humanistic outcomes in patients and caregivers. Herein, we report a cross-sectional analysis of the baseline data of persons with haemophilia (PWH) participating in the prospective study HEMOLIFE. These data are part of a prospective, observational, and multicentre study currently being conducted in 20 hospitals in Spain by haematologists. We included subjects 12 years or older diagnosed with haemophilia. The evaluations included the Maladjustment Scale, Haemophilia-Specific Quality of Life Questionnaire for Adults (HaemoQol)/HaemoQol Short Form (Children), haemophilia-specific version of the Work Productivity and Impairment Questionnaire plus the Classroom Impairment Questionnaire (WPAI+CIQ:HS), Haemophilia Activity List (HAL)/Paediatric Haemophilia Activities List (pedHAL), visual analogue scale (VAS) for evaluating pain, Coping Pain Questionnaire-Reduced (CAD-R), and Hospital Anxiety and Depression Scale (HADS). A total of 81 PWH were recruited at 18 centres; 66 PWH were ≥18 years (i.e., adults), and PWH 15 were <18years (i.e., paediatric patients). Out of the 79 evaluable subjects, 16 (20%) showed an impact of haemophilia on daily life, and the areas most affected were "leisure time" (58% showed maladjustment) and "work/studies" (47% showed maladjustment). Patients reported a higher impact of haemophilia on quality of life (mean [SD] of the transformed score) in the dimensions of "sport" (49.4 [28.6]), "physical health" (40.5 [25.8]) and "future" (37.7 [28.9]). In adults, according to HAL scores, greater impairment of function was observed in "lying/sitting/kneeling/standing," "function of legs" and "leisure activities and sports," with mean normalized scores of 64.7, 65.1 and 69.0, respectively. Productivity was mostly impacted by presenteeism. The pain was infrequent and moderate. According to the HADS scores, nine (11.5%) patients had clinical anxiety and depression. PWH without inhibitors exhibited impairments in adjustment, quality of life and functionality, especially related to leisure and sports activities, and exhibit relevant levels of anxiety and depression.

Haemophilic arthropathy: Diagnosis, management, and aging patient considerations.

Gene therapy and universal use of safer, more effective, and personalised prophylactic regimens (factor, and nonfactor) are expected to prevent joint bleeding and promote joint health in persons with haemophilia (PwH). Growing evidence suggests that subclinical bleeding, with active and inactive synovial proliferation, continues and haemophilic arthropathy remains a major morbidity in PwH despite early institution of joint prophylaxis. Joint health assessment is evolving with physical examination scores complementing imaging scores. Point-of-care ultrasound is emerging as a safe, cost-effective, and readily available tool for acute determination of musculoskeletal abnormalities, serial evaluation of joints for sonographic markers of haemophilic arthropathy, and in providing objective insight into the efficacy of new therapies. In acute haemarthrosis, arthrocentesis expedites recovery and prevent the vicious cycle of bleed-synovitis-rebleed. When synovial proliferation develops, a multidisciplinary team approach is critical with haematology, orthopaedics, and physiotherapy involvement. Synovectomy is considered for patients with chronic synovitis that fail conservative management. Non-surgical and minimally invasive procedures should always be offered and considered first. Careful patient selection, screening and early intervention increase the success of these interventions in reducing bleeding, pain, and improving joint function and quality of life. Chemical synovectomy is practical in developing countries, but radioactive synovectomy appears to be more effective. When surgical synovectomy is considered, arthroscopic/minimally invasive approach should be attempted first. In advanced haemophilic arthropathy, joint replacement and arthrodesis can be considered. While excited about the future of haemophilia management, navigating musculoskeletal challenges in the aging haemophilia population is equally important.

Unresolved hemostasis issues in haemophilia.

Despite rapid technological advancement in factor and nonfactor products in the prevention and treatment of bleeding in haemophilia patients, it is imperative that we acknowledge gaps in our understanding of how hemostasis is achieved. The authors will briefly review three unresolved issues in persons with haemophilia (PwH) focusing on the forgotten function that red blood cells play in hemostasis, the critical role of extravascular (outside circulation) FIX in hemostasis in the context of unmodified and extended half-life FIX products and finally on the role that skeletal muscle myosin plays in prothrombinase assembly and subsequent thrombin generation that could mitigate breakthrough muscle hematomas.

How much prophylaxis is enough in haemophilia?

Prophylaxis has become standard of care for all persons with haemophilia (PWH) with a severe phenotype. However, 'standard prophylaxis' with either factor or non-factor therapies (currently only emicizumab available) is prohibitively expensive for much of the world. We sought to address the question of 'How much prophylaxis is enough?' and 'Can it be individualized?' and specifically 'Can emicizumab be individualized?'. We reviewed the literature on prophylaxis in haemophilia since its inception in the 1950s to the present, the development of more and less intense factor prophylaxis regimens and their outcomes and additionally the published outcomes of prophylaxis with low dose emicizumab. What these experiences collectively show is that low dose emicizumab does result in significant benefits to patients whilst being much less expensive than a "one size fits all" emicizumab prophylaxis approach. We also took note that some non-factor therapies still in development are individualized given that high doses of these can potentially put patients at risk. Prophylaxis is now clearly accepted as standard of care for PWH with a severe phenotype but now in a very short time a large assortment of different treatment options for prophylaxis have become/are becoming available and the haemophilia community will need to determine how to best use these recognizing that no 'one treatment fits all'.

Defining success in haemophilia care - Are we doing it right?

Transformational advances have occurred in the management of haemophilia in the last decade leading to much better outcomes. However, a detailed and critical examination of its assessment and reporting show gaps in many aspects. These are discussed in this review. The relevant literature related to different aspects of management of haemophilia was reviewed to identify gaps which need to be addressed. These include detection and diagnosis of haemophilia, documentation and reporting of joint bleeding, its management and methods of reporting in clinical trials and practice, aspects of personalizing care as well as access to therapeutic products and the need for and organization of comprehensive care. Current diagnostic approaches have more than doubled the identified number of persons with haemophilia (PWH) over the last 25 years but still constitute only ∼30% of the expected number. Joint bleeding is the primary indicator of disease severity and treatment efficacy, but there is lack of consistency and standardization in the way it is recorded and reported. Its continued use as an efficacy measure of modern treatments which maintain steady state factor levels or equivalence of>5% will lack sensitivity. The treatment of acute haemarthrosis has focussed on haemostasis and pain control, ignoring the role of inflammation in joint damage. Phenotypic heterogeneity of severe haemophilia has recognized clinical and laboratory variations based on haemostasis but not differences in local response to blood in the joint. At the organizational level, IU/capita provides a relevant measure of access to therapeutic products when the detection rate is ∼100% but is fallaciously low when detection rates are very low. With highly effective modern therapies for haemophilia and nearly no bleeding, the concept of comprehensive care team will need modifications. As haemophilia care advances, a deeper dive is needed into the details of various aspects its management to ensure consistency and contemporary relevance.

Non-surgical correction of knee flexion deformity in persons with haemophilia: A staged multidisciplinary approach.

Flexion deformity of the knee is a common complication following recurrent haemarthrosis in persons with haemophilia (PWH) on episodic factor replacement therapy, restricting independent mobility. There is limited literature on the comprehensive management of this condition. This report provides the outcome of a staged multidisciplinary approach for the correction of knee flexion deformity (KFD) even in limited resource settings. The data of 49 consecutive PWH who were treated for KFD were analysed. The approach included graded physical therapy (PT), followed by serial casting and/or mobilisation under anaesthesia (MUA). MUA was done in carefully selected knees. Surgical correction was opted when non-surgical methods failed. Of the 49 patients (55 knees), with a median KFD of 40 degrees (range: 10-90), 26/55 (47%) were corrected by graded PT. With serial casting, 9/19 (47%) knees had their KFD corrected. MUA was done for 11 knees of which five achieved correction (45%). Surgical correction was required for only seven knees (12.7%). Following this approach, KFD improved from 40 degrees (range: 10-90) to 15 degrees (range: 0-40), with only minor loss of flexion from 105 (range: 60-155) to 90degrees (range: 30-150). Out of 55 KFD, 46 (83.6%) KFD were corrected; non-surgical, 39 (70.9%) and surgery, seven (12.7%). The remaining patients (nine KFD; 16.4%) were able to achieve their functional goal despite not meeting the correction criteria. This study shows that in PWH, functionally significant KFD correction can be achieved in about 71%, through non-surgical methods, even without prophylactic factor replacement.

Coping Patterns and Psychosocial Distress in Hemophilia Patients: A Cross-sectional Study from South Gujarat, India

Abstract Introduction: Hemophilia is hereditary genetic disorder with defects in normal blood clotting mechanisms. It is characterized by a chronic course requiring lifelong treatment. Persons with hemophilia (PWH) are known to have significant stress due to socio-occupational impairments caused due to the illness. It affects the treatment outcomes adversely. There are few studies from India that have looked at the factors and prevalence of psychiatric comorbidities in this population. Aim: To study coping patterns, perceived stress, anxiety, and depression profiles in adult patients of hemophilia. Materials and Methods: A purposive sample of 52 PWH was collected. We used a semi-structured questionnaire to obtain demographic data, illness profiles, and experience of complications and concerns of the participants. Scales used were Beck’s depression inventory, Anxiety scale, Holmes and Rahe Social Readjustment Rating Scale scale, and COPE questionnaire. Results: About 41% of the individuals had depression and 26.92% of individuals had trait anxiety. The state-dependent anxiety was seen in 69%. About 50% were found to be susceptible to stress-related illness. The adaptive coping style, namely, problem-focused coping, was associated with lower scores on the screening instruments. The presence of certain complications was associated with higher use of maladaptive coping strategies like the use of emotion and avoidance-focused coping. Conclusions: Considering the impact and morbidity, screening for psychological distress and analysis of coping styles of PWH should be a part of routine care.

Proactive Systematic Hemophilia Carrier Screening: A Step Towards Gender Equity in Hemophilia Care

Introduction Despite multiple awareness-raising initiatives, and in contrast with male persons with hemophilia (PwH), a considerable number of carriers and female PwH still go undiagnosed. We here present the findings of a proactive and extensive hemophilia carrier screening project. Methods From May 2021 until April 2023, potential and obligate carriers of hemophilia A (HA) and B (HB) were identified by updating family trees of all PwH regularly followed at the Cliniques universitaires Saint-Luc. Data from previously screened female individuals (bleeding history, coagulation factor assays and testing for the index patient's pathological genetic variant) were collected retrospectively through electronic medical records (EMRs). Female individuals who had not been previously screened or with missing data were provided with a total of 125 invitation letters by related index hemophilia patients. The study protocol received approval of the local ethics committee. Results All 287 male PwH (226 HA, 61 HB) from 228 families (180 HA, 48 HB) were included in the analysis. Seven female PwH (3 HA, 4 HB) were considered as index cases in their families. In total, based on the family trees, there were 900 females, among which 454 were obligate and/or genetically proven carriers of hemophilia and 118 were found to be non-carriers (Figure 1). Mean age at diagnosis was 30.7 years (range 1-82) in families with HA and 30.1 years (range 0.5-93) in families with HB, without significant difference between these two groups (p=0.809) or between families with severe, moderate or mild hemophilia (p=0.535). Genetic testing for pathological variants has been conducted in 133 obligate, 237 potential and 4 sporadic carriers, and remains to be performed in 190 obligate and 328 potential carriers. Eight females were obligate non-carriers. The group of mothers, sisters and daughters of PwH comprised 543 females, of which at least 178 (35.7% of those with known date of birth) were of reproductive age (18-49 years). Seventy-three percent of females in the latter group have had genetic testing. The proportion of female individuals genetically tested did not significantly differ between families of different severities of HA (p=0.132). In families with moderate HB, female individuals were more likely to be tested (genetic status known in 59.4%) than in other HB severity groups (p=0.01), yet this may be attributed to the presence of one large family comprising 6 male persons with moderate HB and 22 female individuals, of whom a large proportion (n=18, 82%) has had genetic testing. Among carriers with known coagulation factor levels (261/454), 42 (23.0%) and 23 (29.5%) carriers of HA and HB, respectively, had a factor level below 40 IU/dL, and 65 (35.5 %) and 32 (41.0%) had a factor level below 50 IU/dL. The proportion of carriers with a factor level below 40 IU/dL did not significantly differ between families with severe, moderate and mild hemophilia (22.6%, 34.7% and 22.7% respectively, p=0.213), neither did mean coagulation factor levels in carriers with a factor deficiency in these groups (26.2, 30.4 and 27.1 IU/dL in families with severe, moderate and mild HA and HB, p=0.344). Carriers with a coagulation factor deficiency of less than 40 IU/dL were screened earlier than other female individuals (mean age at diagnosis 25.8 and 31.8 years, respectively, p=0.034). Conclusions This study represents the first reported attempt to systematically identify all (potential) hemophilia carriers within families of all PwH followed at a single hemophilia treatment center. To date, this initiative has allowed 44% of the entire cohort to be screened, and carrier status to be genetically confirmed in 73% of mothers, sisters and daughters of PwH who are of childbearing age, based on the date of birth documented in their EMR. Although original and promising, these data reflect the major challenges and difficulties in reaching out and providing appropriate screening to all women genetically linked to one or more PwH. The carrier screening efforts that have been initiated in our center, and which should ideally be replicated across the hemophilia community globally, appear as a critical step towards providing equal access to haemophilia diagnosis and care to all potentially affected individuals, regardless of their gender.

Reporting of Race and Ethnicity and Representation in Hemophilia Clinical Trials

Background: Racial and ethnic representativeness in clinical trials is a crucial step to mitigate disparities in outcomes. In 2017, the United States (US) Food and Drug Administration (FDA) issued a final ruling requiring trial sponsors to report race/ethnicity data to the clinicaltrials.gov registry. Black and Hispanic persons are underrepresented in clinical trials for several diseases, including hematologic malignancies (Hantel, Luskin et al. 2021). However, the reporting and representation of race and ethnicity for hemophilia interventional trials is unknown. Congenital Hemophilia is a rare bleeding disorder for which there have been significant treatment advances leading to substantial gains in life expectancy and improvements in quality of life for those with access to treatment. The aims of the current study are to assess 1) the frequency of race and ethnicity reporting; and 2) the racial and ethnic distribution of participants in interventional clinical trials enrolling persons with hemophilia (PwH). Methods: In this cross-sectional study, the clinicaltrials.gov database was queried in April 2023. All studies with “hemophilia” as the condition, coded as “interventional” and with “results” were selected (n=157). The proportion of trials reporting race/ethnicity and the distribution of race/ethnicity based on the US Office of Budget Management Categories (OBM) was computed according to trial characteristics. The racial/ethnic distribution of trial participants (observed) was compared to what would be expected based on United States (US) hemophilia treatment center (HTC) data and census data from four countries (Brazil, Canada, United Kingdom, and US) with observed-to-expected ratios (O/E) and 95% Confidence Intervals (CI). Results: Of the 157 trials identified, 28 were excluded because they were prematurely terminated. Of the 129 completed trials, the completion year ranged from 2007 to 2022, the large majority were industry sponsored (94.6%), and included an average of 62 participants with an average age of 26.8 years. Overall, 52.0% (n=66) of trials reported race/ethnicity data, which increased from 41.0% before 2017 to 100% in 2017 or later (p-value=.001) (Table 1). Among the 66 trials that reported race/ethnicity data, 49 (74.2%) were conducted in two or more countries, and the most common sites included the US (n=42 trials, 63.6%), Italy (n=26, 39.4%), Poland (n=24, 36.3%), Germany (n=22, 23.3%), and France (n=22, 33.3%). In terms of race/ethnicity, 65.1% of trial participants were White, 22.6% were Asian, 5.0% were Hispanic, 3.9% were Black, 2.3% were other race/ethnicity, and 3.8% were missing data on race/ethnicity. The proportion of trial participants who were White was approximately 20% lower than the US HTC population (O/E=0.83, 95%CI 0.80, 0.86) and 10-20% lower than the total population of the US (O/E=0.85, 95%CI 0.82,0.87), United Kingdom (O/E=0.80, 95%CI 0.78, 0.82), and Canada (O/E=0.91, 95% CI 0.88, 0.94) (Table 2). The proportion of trial participants who were Black or Hispanic was approximately 75% lower than the US HTC and the US total population. The percentage of trial participants who were Asian was 1.6 to 3 times higher than general population in the US, Canada, and UK (Table 2). We were unable to assess the number of racial/ethnic minorities enrolled in the US as these detailed data are not reported in clinicaltrials.gov. Another limitation is that ethnicity definitions vary across country's censuses. Conclusions: Our study found that less than half of interventional hemophilia trials conducted before the 2017 FDA requirement to collect data on race/ethnicity did so, whereas all trials conducted in 2017 and later reported race/ethnic data. Compared to the US HTC and total population, Black and Hispanic people with hemophilia are especially underrepresented in hemophilia interventional trials. In 2020, the US FDA provided guidance on eligibility criteria, enrollment practices, and trial designs to increase diversity in underrepresented racial and ethnic participants. Rare diseases, including hemophilia, require additional efforts to improve diversity in clinical trials given the smaller patient population (The FDA, 2020). These efforts may include engaging patient advocacy groups in the trials process and leveraging international HTC networks.

Assessment of Haemophilia Patients' and Other Bleeding Disorders Needs of Psychosocial Support and Health Care Needs and Their Utilization in Haemophilia Treatment Centres (ILLUSTRATE Study)

Background: Psychological support for chronically ill patients as an integral component of medical care could improve health-related quality of life (HRQoL) of patients and contribute to a reduction in treatment costs. A meta-analysis including almost 3,000 patients revealed that persons with hemophilia (PWH) are at increased risk for depression, anxiety, and ADHD compared to the general population (Al-Huniti et al., 2020). Studies have shown that the self-efficacy, coping mechanisms, and HRQoL of parents of hemophilic children were improved by self-help programs, and depression, anxiety, and parenting stress were reduced. Although different psychological interventions have been used to help PWH to cope with their psychological problems, there is a gap between patients' need for psychosocial support from the perspective of health care professionals (HCPs) and their utilization by PWH. The aim of the ILLUSTRATE study was to assess the need for psychosocial support and medical care in patients with inherited bleeding disorders (IBD) and in HCPs and their use in hemophilia centers. Methods: Patients with IBD (PIBD) were invited by different German patient organizations (Deutsche Bluthilfe, DHG, IGH, Hämophilie 2000) to participate in an on-line surevey (from December 2022-June 2023). In addition, HCPs were asked to complete a similar on-line survey via the mailing list of the German Society for Thrombosis and Hemostaseology. A positive ethical approval for the study was obtained by the Local Psychological Ethics Committee at the University Medical Centre in Hamburg, Germany (LPEK-0578). The questionnaire for patients consisted of the following aspects: socio-demographic data, medical background, care services and psycho-social support, dealing with stress and difficult situations, dealing with special situations that may arise or be exacerbated by the bleeding disorder, offer of psycho-social counseling/support, and need for expansion. The questionnaire for HCPs contained the following themes: personal background, need of patients for psycho-social counseling/support (PSCS), supply of PSCS and need for expansion, utilization, and benefits of PSCS. Results: In total, 154 patients and parents of children with an IBD participated (72 PIBD,80 parents, 2 others) with a mean age of 41.06±13.3 years, 60.4% were female. In addition, 65 HCPs completed the respective survey (34 physicians, 27 nurses and 4 others) with a mean age of 48.11 ± 12.7 years, in average they worked since 13.1±10.8 years in haemostaseology, 78.5% worked in a hemophilia comprehensive care center (HCCC), 20% in a hemophilia treatment center (HTC) and 1.5% in a homecare service. In the IBD group (patients, parents) most were married (59.1%), lived with a partner (83.8%) and worked full- or part-time (66%). Most PIBD had hemophilia (74%) with a severe form (81.8%). 28.6% of the IBD group felt little to not at all supported to overcome psycho-social challenges. It was demonstrated that they had an intermediate stress resilience (14.76±3.1), with 1/3 showing a low resilience. When asking what coping strategies they used in stress situations, 26% mentioned that they ignore difficult situations and 16% compensated their stress with drugs and alcohol. 20% often to always felt helpless and overwhelmed due to their IBD and 31% rarely to never received support in these situations. 71% reported to have a need for PSCS, 57% wished more support services (69% mainly at the HTC), 71% felt not to have enough information about these services and 64% would use them more often if they were more accessible. 52% of HCPs found that the IBD group has a need of PSCS, they assumed that parents and adolescent patients would benefit most of these services and expected the highest advantage from psychological counseling. 60% thought that there is a need for information and education. The IBD group and HCPs preferred PSCS in presence, the IBD group would use services as well via phone or digital. Conclusions: Although offered psycho-social support programs are rarely used by patients, a large proportion of the IBD group and HCPs confirmed a need for it. Increased accessibility to PSCS and more information were identified as a factor for increased use of this support programs. Additional digital psycho-social support services were desired and represent a helpful alternative if services are not available on site.

Appraising Haemophilia Caregivers Burden in the Resource-limited Setting: A Nigerian Survey

Abstract Background: Inadequate management of haemophilia in a resource-limited setting may worsen the challenges that haemophilia caregivers face. Aim: The aim of the study was to evaluate the effect of the burden of caring for persons with haemophilia (PWH) on the quality of life of the caregivers. Methods: This was a cross-sectional national survey carried out among caregivers of PWH. A modified CarerQol-7D Questionnaire was distributed to consenting families with PWH. The association between clinicopathological characteristics of care recipients and these outcome variables was calculated by SPSS version 22. Results: One hundred and five families participated. The majority of the caregivers were immediate family members (101, 96.2%) and mothers (75, 71.4%) of patients. Caregivers were five times more likely to experience a lot of personal mental health problems when taking care of a PWH of severe phenotype (odds ratio [OR]: 4.55, 95% confidence interval [CI]: 1.13–18.32) and when rendering care to a recipient that experienced ≥6 serious bleeds a year (OR: 3.94, 95% CI: 1.02–15.18), respectively. Caregivers were also found to be 12 times more likely to experience a lot of physical health problems when taking care of wheelchair-bound PWH (OR: 12.00, 95% CI: 0.89–161.65). Conclusion: Improved treatment of haemophilia with the establishment of a support system may be key in easing the burden of caregivers in resource-limited settings.

Health and emotional regulation among persons with hemophilia

The psychosocial status of people with chronic ailments has garnered undivided attention in recent years, especially for diseases such as Aids, leukemia, and hemophilia. Numerous clinical and psychological issues associated with hemophilia have been found to attribute a significant increase in emotional distress. Due to the paucity of research on the psychosocial aspects of this inherited disorder. The aim of the research was to study emotional reappraisal, emotional suppression, and health among persons with hemophilia. A total of 50 patients participated in the study and were divided into 2 age groups (19-24) and (25-30). Standardized scales such as Emotion Regulation Questionnaire (Gross &amp; John, 2003) and Patient Health Questionnaire (Spitzer et. al, 1999) were used. The obtained results were tabulated, and correlation and independent t-tests were used to compare the means of two age groups. The total sample mean was found to be 18.10 and the standard deviation was 8.30 respectively. The correlation of health was found to be positive and significantly related to emotional reappraisal (r= 0.10) and emotional suppression (r=0.08). The result portrays there is no difference between the two age groups on emotional regulation and health. Despite much research on the genetic causes of this condition in India, there is a dire need to study the psychological challenges, social problems, and opportunities available to persons with hemophilia (PWH). Psychological and genetic counseling shall be promoted for the holistic well-being of hemophiliacs.

PB0177 An Examination of Access to Preventive Therapies for Persons with Hemophilia (PWH): A Pilot Survey on Behalf of the International Prophylaxis Study Group (IPSG)

PB0177 An Examination of Access to Preventive Therapies for Persons with Hemophilia (PWH): A Pilot Survey on Behalf of the International Prophylaxis Study Group (IPSG)

Mobilization under anaesthesia for correction of knee flexion deformity in haemophilia.

Haemophilia patients not treated with primary or secondary prophylaxis, often present with recurrent haemarthrosis. Knee is the most frequently involved joint leading to disabling knee flexion deformity (KFD). Here, we present a retrospective study of our experience on the role of mobilization under general anaesthesia in the correction of KFD. To study the effectiveness of mobilization under anaesthesia (MUA) for correction of knee flexion deformity (KFD) in persons with haemophilia (PWH). Outcome of all patients managed with MUA in our multidisciplinary haemophilia clinic from 2008 to 2019 were included for analysis. PWH with KFD>20 degree who underwent MUA were included in the study. Under general anaesthesia and cover of clotting factor replacement, gentle joint mobilization was done to achieve maximal correction in flexion deformity, followed by above knee casting in this position. The outcome measures assessed were reduction in knee flexion deformity following MUA and complications, if any. Thirty patients (34 knees) with knee flexion deformity were included in the study. Mean age of the study population was 14.23 years ± 8.3. Study population was analysed in two groups, Group 1 included patients who underwent single MUA and Group 2, patients who underwent two or more MUA. There was significant improvement in KFD correction in both groups. [Group 1; Mean difference: 22 ± 13.7, p value -0.01, 95% CI (16.4-27.5) and Group 2; Mean difference 48.8 ± 19.8, p value -0.00, 95% CI (34.2-64.5)]. MUA can be effective in the short-term correction of KFD in PWH particularly those below 15 years of age. It should be done judiciously when target correction is not achieved with other physical methods.

Evaluation of treatment and outcome for patients with haemophilia A and haemophilia B on extended half-life (EHL) factor products: A 12-month data analysis.

Extended half-life (EHL) factor VIII and IX concentrates as prophylaxis against bleeds have been available to selected persons with haemophilia (PWH) in Australia since March 2018. Preliminary analysis of switching to EHL demonstrated increased treatment adherence, fewer injections and improved bleeding outcomes. To characterise clinical practices regarding the use of EHL in Australia, to further evaluate treatment regimens and bleeding outcomes, and to analyse the influence of EHL product pharmacokinetics on clinical decision-making. A national, retrospective study was conducted using the Australian Bleeding Disorders Registry (ABDR). Patients on EHL products during the entire 2019 calendar year were included for analysis. A complete and validated dataset of 174 PWH was analysed, 115 Haemophilia A (HA) and 59 Haemophilia B (HB). Adherence to EHL therapy was 85.7% in HA and 87.2% in HB. About 63.5% of HA and 64.4% of HB PWH reported zero spontaneous bleeds over 12months. Ankles were the most frequent spontaneous bleed site. Approximately one-third patients underwent dose adjustments, with most frequent reasons being pharmacokinetics, body weight change and breakthrough bleeds. About 19.5% of PWH had target joint history, with spontaneous bleeds reported in 58% of that cohort on EHL. Multivariate regression showed significant impact of non-adherence, target joint history and short half-life on spontaneous bleeds in the HA cohort; however only short half-life had significant impact in the HB cohort. EHL usage in Australia shows excellent treatment adherence and bleeding outcomes. This study affirms the use and value of widely available population-based pharmacokinetics as a clinical tool.

Residual burden of liver disease after HCV clearance in hemophilia: a word of caution in the era of gene therapy

AbstractRuling out advanced fibrosis/cirrhosis is mandatory for persons with hemophilia (PWH) who are candidates for gene therapy. However, clinical evaluation and noninvasive tests (NITs) may be inaccurate after hepatitis C virus (HCV) clearance. We conducted a prospective hepatological screening to detect advanced fibrosis/cirrhosis in PWH after HCV clearance. Any risk factor of chronic liver damage was registered by using biochemical data, liver stiffness measurement (LSM), and ultrasound (US). A pre/post-HCV clearance analysis was conducted prospectively in a subgroup of patients who underwent LSM, US, and NITs for fibrosis. We evaluated 119 patients (median age, 53 years; range, 36-87 years) with a previous HCV infection (hemophilia A, n = 108; hemophilia B, n = 11). Ninety-six (81%) presented at least 1 potential risk factor of chronic liver damage. Metabolic risk factors were the most prevalent, with 51 patients (44%) having US steatosis. In 21 patients (18%), clinical, biochemical, liver morphology, and/or LSM were suggestive of advanced fibrosis/cirrhosis. Furthermore, 10 patients (8%) had esophageal varices and 3 (3%) had hepatocellular carcinoma. In 57 patients included in the prospective analysis, LSM and NITs were reduced after HCV clearance (P < .05), but US signs specific of cirrhosis remained unchanged. Overall, 23 of 80 patients (29%) with LSM <10 KPa had at least 1 US sign suggestive of advanced fibrosis/cirrhosis. A similar proportion (18%) was observed for LSM <8 KPa. Overall, risk factors of chronic liver damage are frequent after HCV clearance, but changes in LSM and NITs after clearance may be inaccurate to rule out advanced fibrosis/cirrhosis. A specific diagnostic workup is warranted to evaluate liver health in PWH in the era of gene therapy.