Persons With Haemophilia Research Articles

Pain assessment and management in Italian Haemophilia Centres.

Although the widespread use of factor VIII/IX replacement therapy has significantly reduced the severity of arthropathy in persons with haemophilia (PWH), some develop degenerative joint changes, associated with significant pain. The aim of this survey was to investigate the management and perception of pain among Italian physicians who treat PWH. Between September and October 2017, a questionnaire was distributed to 35 Italian haemophilia treatment centres (60 physicians). Fifty-three haemophilia specialists completed the survey. We found that there was good agreement (98.1%) on the need to investigate pain at each clinical visit, but there was heterogeneity in the opinions of haemophilia specialists with regards to the availability of validated guidelines (35.8%) and whether pain specialists should be a part of the comprehensive care team in daily clinical practice (58.5%). Haemophilia specialists also agreed pain should be evaluated using a rating scale validated in PWH (88.7%). Pain was mainly managed by the haemophilia specialists themselves, supported by a physiatrist and physiotherapist, while a pain specialist was only involved in 26.4% of cases. The combination of paracetamol with tramadol or codeine was the most common first-line treatment, while cyclo-oxygenase-2 inhibitors, non-steroidal anti-inflammatory drugs, and opioids were less commonly used. There are some unmet needs in Italy regarding pain management for PWH and the management of pain in these patients by haemophilia specialists. There is a lack of evidence-based guidelines for these specialists to use, as well as a reluctance to involve pain specialists. The lack of spontaneous reporting of pain by PWH, despite using pain relief, highlights the need for clinicians to actively ask patients about any pain they may be experiencing.

Reimbursing the value of gene therapy care in an era of uncertainty.

Early-stage gene therapy (GT) clinical trials are demonstrating exciting results for persons with haemophilia (PWH), with the first products possibly licenced over the next few years for haemophilia A and B. These new treatments offer the possibility of a one-off approach to the treatment of haemophilia, with demonstrated increases in factor level expression and substantial reductions in both bleeds and factor utilization. However, clinical trial participants have demonstrated variable expression in factor levels, including decreases, over time, suggesting in some cases the effect may not last. The consequence of this uncertainty has led to challenging discussions on value and reimbursement. In most national healthcare systems, the relatively high cost of paying for GT on a one-off basis may be prohibitive, resulting in a lack of access and less post-marketing data generated, ultimately keeping these performance uncertainties high for payers. Economic models have demonstrated the cost-effectiveness of GT in haemophilia based on current clinical trial inputs, but it is in the certainty of these inputs and concomitant budget impacts where the lack of available data will be a concern for payers. To overcome the 'chicken and egg' discussion in relation to reimbursement and data, GT will necessitate new pricing and reimbursement models that share the risk between the manufacturer and the payer. New models have been described for other conditions. The aim of this paper is to propose illustrative concepts of haemophilia reimbursement models that may be further considered in the assessment of a less predictable therapeutic such as GT.

Risk of Hypertension in Hemophilia Patients with a History of Inhibitors

Hemophilia is an X-linked bleeding disorder characterized by deficiencies of Factor VIII or IX. Hypertension in persons with hemophilia (PWH) appears to be more prevalent compared to the general population. A major complication of hemophilia remains the development of neutralizing antibodies (inhibitors) against infused clotting factor. It tends to occur within the first 50 exposure days and therefore mostly in children with severe hemophilia. Since inhibitor development is associated with high mortality and morbidity, their eradication with high dose clotting factor concentrates is critical and successful in the majority of patients. Recently a cohort study showed a positive association between presence of inhibitors in elderly patients and cardiovascular disease, although a small number of patients with inhibitors were included in that study (Sood SL, Blood Advances 2018). To date, the link between a history of inhibitors and hypertension has not been established. The primary purpose of our study was to evaluate the relationship between hypertension in PWH and a history of inhibitors, with the additional goals of investigating the association between hypertension and hemophilia type and viral status. In a retrospective review, clinical records were extracted for PWH aged 18 to 79 between 2003 and 2014 from four Hemophilia Treatment Centers in North America: Los Angeles Orthopaedic Hospital, University of California San Diego, Tulane University and University of British Columbia. We extracted demographic information on age and ethnicity, weight, height, hemophilia type and severity, inhibitor history, Hepatitis C (HCV; by serology) and Human Immunodeficiency Virus (HIV) status or reported history thereof and medication history. Primary outcomes were prevalence of hypertension stratified by inhibitor status, hemophilia type, and presence of viral coinfection. Blood pressure measurements were taken for the three clinic visits closest to the evaluation date. We fitted generalized additive models with a non-parametric spline function for age. The outcomes were hypertension (with a binary logit), systolic blood pressure (SBP) and diastolic BP (DBP). The models were adjusted for logBMI, type of hemophilia, severity, race/ethnicity, HCV and HIV. We plotted standardized curves generated by the models to compare trends in each outcome. A total of 691 PWH were included. Forty-four (6%) had a history of inhibitors, 533 had hemophilia type A (77%) and 157 had hemophilia type B (23%). HCV was positive in 419 patients (61%) and HIV in 128 patients (19%). There was no difference in the risk of hypertension between patients with or without a history of inhibitors. SBPs and DBSs were only analyzed for patients not on anti-hypertensives, and were not associated with a history of inhibitors (Fig. 1A). However, risk of hypertension was considerably higher among patients with Hemophilia B compared to patients with Hemophilia A (Fig. 1B). Hemophilia B patients were more likely to be categorized as hypertensive because both SBPs and DBPs were higher, especially in patients between 40 and 60 years of age. Finally, risk of hypertension was higher among those coinfected with both HCV and HIV (Fig. 1C). This large-scale study found no evidence that inhibitor history influenced the risk for hypertension or elevated BPs in PWH. Interestingly, Hemophilia B was associated with a higher risk of hypertension and higher BPs, similar to prior studies showing Hemophilia B had 1.87-fold higher odds of hypertension compared to Hemophilia A (von Drygalski A, Hypertension, 2013). Inhibitor development in Hemophilia B is very rare, which provides additional support that factors other than inhibitors play a role. Finally, our study showed coinfection with HIV and HCV was associated with higher hypertension risk, adding clarity to inconsistent findings on the association between hypertension and blood transmitted viral diseases in PWH. While there was no evidence that patients with a history of inhibitors have a higher risk of hypertension, our observations add to the continued efforts to elucidate the etiology of the hypertension in hemophilia and confirm that patients with Hemophilia B and/or viral infections may be at higher risk. These findings continue to inform medical care and also pave the way for additional studies to address physiological factors inherent to hemostasis and vascular pathology. Disclosures Kruse-Jarres: NovoNordisk: Other; CSLBehring and Genentech/Roche: Research Funding; Biomarin, Chugai, CSLBehring, and Genentech/Roche: Consultancy. Quon:Orthopaedic Institute for Children: Current Employment; Bayer: Honoraria; Shire/Takeda: Speakers Bureau; Genentech, Inc./F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Octapharma: Honoraria; Novo Nordisk: Honoraria, Speakers Bureau; Bioverativ/Sanofi: Honoraria, Speakers Bureau; Biomarin: Honoraria, Speakers Bureau. Jackson:Octapharma, Takeda, Bayer, Roche and Pfizer: Honoraria; Bayer: Research Funding; Sanofi: Research Funding. von Drygalski:Hematherix Inc: Membership on an entity's Board of Directors or advisory committees, Other: Cofounder; superFVa; Joint Activity and Damage Examination (JADE) Ultrasound measurement tool: Patents & Royalties; Biomarin, Bioverativ/Sanofi-Genzyme, Novo Nordisk, Pfizer, Uniqure, Takeda: Consultancy.

Management and Outcomes of Persons with Hemophilia Undergoing Endoscopies: A Single Hemophilia Treatment Center Experience

INTRODUCTION The need for factor concentrate (FC) prior to uncomplicated endoscopies in persons with hemophilia (PWH) is not well characterized. Infusion of FC is time consuming, costly, and increases risk of inhibitor development. There is no general consensus on management of PWH undergoing endoscopies and the incidence of bleeding is not well established. At our Hemophilia Treatment Center (HTC), our standard of care (SOC) for many years was to manage PWH with an infusion of FC prior to any endoscopy for any indication regardless of severity of hemophilia. In November 2017, we changed our SOC for persons with mild hemophilia (factor VIII or IX >5%) to use only antifibrinolytics pre-endoscopy for those in whom no procedural intervention was anticipated, followed by infusion of FC post-endoscopy if a biopsy or polypectomy was performed or if there was bleeding associated with the procedure. Persons with moderate or severe hemophilia (factor VIII or IX ≤5%) continued to receive infusion of FC prior to all endoscopies. We report our experience managing PWH of all severities undergoing EGD and colonoscopy between 2008 and 2019. We compare incidence of bleeding, cost of medical care, and outcomes before and after the change in SOC for persons with mild hemophilia. METHODS Subjects were identified from a database of patients treated at our HTC. Those with factor VIII inhibitors were excluded. Cost of FC and antifibrinolytics were determined from average wholesale pharmacy prices in 2019. Gastrointestinal (GI) bleeding was assessed by review of medical records within 30 days after endoscopy. Documentation of any patient or clinician reported hematemesis or rectal bleeding, requiring or not requiring medical attention or treatment, was recorded as GI bleeding. Adequacy of hemostasis, as assessed by review of medical records, was classified as poor if the subject had unexpected hypotension, required intensive or intermediate care, or transfusion; fair if unplanned doses of FC were required, but the event did not meet criteria for poor hemostasis; and excellent for events that did not meet any of the above criteria. RESULTS Sixty-seven subjects met eligibility criteria; 12 were excluded due to inadequate records of endoscopies. Data were collected on 110 endoscopies performed in 55 subjects, range 1 to 5 per subject. Subject demographics are noted in Table 1. Endoscopy characteristics and outcomes are shown in Table 2. GI bleeding occurred within 30 days after 10 endoscopies prior to the change in SOC. This included 7 endoscopies performed because of preexisting bleeding due to esophageal varices, or gastric, duodenal, or colonic ulcers. In addition, post endoscopy bleeding occurred in one patient after colonoscopy following the use of hot snare cautery resection of polyps, and in another after resection of a rectal polyp by cold snare following an EGD with colonoscopy. No GI bleeding occurred within 30 days of the endoscopies performed after we changed our SOC. FC was used prior to 97.1% of 68 endoscopies performed before we changed our SOC, compared to 73.8% of 42 endoscopies performed after. Hospital stay of 2 days was equivalent across all groups when subjects with preexisting bleeding were excluded. Hemostasis was excellent in 79.4% of endoscopies before we changed our SOC and 100% of endoscopies after. Endoscopy characteristics and outcomes in subjects with mild hemophilia before and after we changed our SOC are shown in Table 3. Reasons for using FC pre-endoscopy in these subjects included preexisting bleeding, planned intervention, or anticipated complex procedure. Treatment costs in subjects with mild hemophilia are noted in Table 4. CONCLUSION We describe our HTC's experience with endoscopies in PWH. In our cohort of persons with mild hemophilia, we demonstrate that the use of antifibrinolytics rather than FC pre-endoscopy did not result in any difference in adequacy of hemostasis or development of GI bleeding within 30 days post endoscopy. This practice was associated with significant cost-savings and no difference of hospitalization rate or length of stay. We conclude that persons with mild hemophilia, who are not actively bleeding or undergoing complex procedures, can be safely managed with antifibrinolytics alone pre-endoscopy. However, patient-specific and procedure-specific factors must be considered when determining the appropriate pre-endoscopy treatment for bleeding prophylaxis in PWH. Disclosures Eyster: Novo Nordisk: Research Funding; SPARK: Research Funding; Sanofi: Research Funding; Baxalta/Shire: Research Funding.

Hematology Utilization Group Studies Part VII (HUGS VII): Costs and Impact of Disease in Older Persons with Hemophilia

BACKGROUD Improved care and prophylactic factor replacement therapy have lengthened life expectancy for persons with hemophilia (PWH). These advancements have created a new hemophilia cohort of senior persons not seen since the previous human immunodeficiency viruses (HIV) years, and little is known about their age-related health outcomes. OBJECTIVES We describe the impact of hemophilia on comorbidities, joint problems, healthcare utilization and health related quality of life (HRQoL) from the HUGS VII baseline data. METHODS HUGS VII prospectively examines the cost and burden of hemophilia, including HRQoL, arthropathy, and economic impact in persons with hemophilia A or B age ≥ 40 years who obtained care from three US Hemophilia Treatment Centers. Participants completed a standardized interview to collect clinical and sociodemographic characteristics, hemophilia treatment regimen, pain, joint problems, comorbidities, and HRQoL using EQ-5D-3L. Clinical chart reviews documented hemophilic severity and treatment. Participants' characteristics were compared between two age groups: 40-49 years and ≥ 50 years using Chi-square tests for categorical variables and T-tests for continuous variables. RESULTS This analysis includes a total of 70 male with hemophilia, 64.3% aged ≥50 years, 75.7% with hemophilia A. Individuals ≥ 50 years had higher rates of being married or with a partner (71.11% vs. 56.0%, P=0.20), retired/not employed (66.7% vs. 28.0%, P=0.002), and having mild or moderate hemophilia (68.9% vs. 40.0%, P=0.02) than those 40-49 years old. Use of prophylaxis was similar among age groups in severe hemophilia but lower for older mild/moderate PWH. Among persons with mild/moderate hemophilia, those ≥ 50 years old reported a higher rate of joint pain (83.8% vs 70.0%, P=0.37) or range of motion limitation (73.3% vs, 60.0%, p=0.45) than the younger group, although the differences were not statistically significant. Compared to those 40-49 years old, individuals ≥ 50 years old reported fewer emergency room visits (4.6% vs. 20.8%, P=0.03), and physical therapy visits (16.0% vs. 41.7%, P=0.06). The older age group had significantly higher rates of self-reported myocardial infarction (11.6% vs. 0%, P=0.08) and diabetes (24.4% vs. 4.0%, P=0.03) than those 40-49 years. Self-reported comorbidities were measured by asking "Has a doctor ever told you that you have certain conditions?" The most frequently reported comorbidities were hepatitis C infection (75.7%, 79.3% of persons with infected hepatitis C had been treated and, 82.7% cleared the hepatitis C virus), hypertension (47.1%), depression (23.2%) and anxiety (21.7%). Mean covariates adjusted EQ-5D index score was lower in older persons (0.79 vs. 0.87, P=0.09). CONCLUSIONS Older PWH are over-represented by individuals with mild/moderate disease, potentially due to premature death among those with severe disease. Although this group included a larger proportion of mild disease than younger PWH, it presented prevalent comorbidities both of aging and of hemophilic arthropathy, despite lower rates of healthcare utilization and use of preventive therapies. Disclosures Curtis: USC Hemophilia Utilization Group Study (HUGS): Consultancy; Patient Reported Outcomes, Burdens and Experiences: Consultancy; Bayer: Consultancy; Novo Nordisk: Consultancy. Konkle:Pfizer: Consultancy, Research Funding; Roche: Consultancy; BioMarin: Consultancy; Sigilon: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Takeda: Research Funding; Uniquire: Research Funding; CSL Behring: Consultancy; Baxalta: Research Funding; Spark: Consultancy, Research Funding. Kulkarni:Sanofi/ Bioverativ, Bayer, Biomarin, Shire/Takeda, Novo Nordisk, Freeline: Other: clinical trial research grants ; Bioverativ/Sanofi, BPL, Genentech, Kedrion, Novo Nordisk, Octapharma, Pfizer, Takeda, Catalyst Bioscience Bayer: Membership on an entity's Board of Directors or advisory committees. Wu:Baxalta US Inc., Bannockburn, IL (a Takeda Company), CSL Behring L.L.C., and Octapharma USA, Inc.: Research Funding. Tran:Takeda: Consultancy; Novo Nordisk: Consultancy; Bayer: Consultancy; Bioverativ: Consultancy. Nichol:Global Blood Therapeutics: Research Funding; CSL Behring: Research Funding; Octapharma: Research Funding; Genentech Inc.: Research Funding; Baxalta US Inc., Bannockburn, IL (a Takeda Company): Research Funding; Pfizer: Research Funding.

Long-Term Follow-Up of a Portuguese Single-Centre Cohort of Persons with Haemophilia and Hepatitis C Virus Infection

Introduction: Persons with haemophilia (PWH) used to represent a population with a high prevalence of hepatitis C virus (HCV) infection due to the use of contaminated blood products. Although the goals of antiviral therapy are the same as the general population, long real-life follow-up data regarding their outcomes are still scarce. Our aim was to report the outcomes of HCV infection and the results of antiviral therapy in PWH. Methods: A retrospective analysis was performed in a single-centre cohort of PWH with positive HCV antibody. Outcomes registered were rate of spontaneous clearance of HCV, sustained virologic response (SVR) achievement, development of end-stage liver disease, and all-cause and liver-related mortality. Results: Out of 131 PWH, 73 (55.7%) had positive HCV antibody. During a median follow-up time of 22 years, 46 patients (63.9%) developed chronic hepatitis C, of which 16 (34.8%) developed cirrhosis. Treatment was pursued in 34 PWH. Most (n = 32) were first treated with interferon (IFN)-based regimens with SVR rates of 40.6%. Direct-acting antivirals were used in 14 IFN-experienced and 2 naïve patients, with an overall SVR rate of 100%. Overall, 17 patients (23.3%) died during the follow-up, only 4 related to liver disease. Of these, none had achieved SVR. Conclusions: We describe the outcomes of a cohort of Portuguese PWH and hepatitis C exposure after two decades of follow-up, with a lower mortality than previously described. Our response rates to HCV treatment were comparable to those in the general population and stress the importance of early treatment.

Biomarkers of bone disease in persons with haemophilia.

Persons with haemophilia (PwH) have abnormally low bone density and increased risk of fractures. We previously demonstrated decreased skeletal health in factor VIII (FVIII)-deficient mice. Thus, we hypothesized factor deficiency is an independent risk factor for decreased skeletal health. We seek to identify differences in bone-related cytokine expression among PwH and healthy controls. We evaluated plasma samples from 79 participants with severe FVIII deficiency and 51 age-matched healthy controls. Plasma samples were assessed for RANKL and OPG, cytokines that regulate bone metabolism, and CTX-1, a biomarker for bone resorption, as well as 10 bone-related cytokines. CTX-1 is higher among samples from FVIII-deficient participants compared to controls (P<.01) but not among participants with recent factor use (within 24hours of sample collection) (P=.21). Among PwH greater than 16years of age (PwH≥16), OPG is increased with recent factor use (P<.01) but not without (P=.34). Lower levels of TNF-α (P<.01), interleukin (IL)-12 (P<.01) and IL-10 (P<.001) were found among samples from PwH. Controlling for subject age, IL-12 and IL-10 levels are lower in PwH≥16 (P<.01, P<.001) but not PwH under 16 (PwH<16) (P>.05). Levels of TNF-α were lower among PwH<16 only (P<.05). These differences are not observed in participants with recent factor use. In PwH, markers of bone metabolism and circulating cytokine levels are abnormal. Recent factor use reverses many of these differences suggesting FVIII replacement ameliorates this pathology. This study suggests bone disease present in PwH is intrinsic to FVIII deficiency.

Unravelling the knowledge, beliefs, behaviours and concerns of Persons with Haemophilia and their carriers in Senegal.

In many sub-Saharan countries, haemophilia exists in an environment of poor knowledge and poor access to treatment. To improve the quality of life of Persons with Haemophilia (PWH), understanding their unmet needs and the socio-cultural realities is essential. This study aims to explore disease knowledge, beliefs, behaviours and concerns of PWH and carriers as a way to find adapted solutions to address the unmet needs. Based on an interview guide, we performed a qualitative study with in-depth interviews of 26 PWH and 14 carriers. Eighty per cent of adult PWH were able to name the severity of haemophilia, but only 32% could describe with accuracy the mode of transmission of haemophilia. Only 23% of carriers were able to inform the severity of the disease. All carriers and adult PWH acknowledged at least one visit to a traditional healer. Acceptance of the disease through religion is the dominant coping strategy observed. High costs of treatment, fear of social rejection, difficulty of management of pain and bleeding at home were the main concerns. Results demonstrate important gaps in knowledge, especially within the carrier population, mothers in Africa playing particularly an important role in the survival and empowerment of PWH. Findings also indicate the important weight of cultural determinants in disease management and behaviours of PWH and thus their important role in the development of educational materials taking into account these determinants.

Management of comorbidities in haemophilia.

With the introduction of clotting factor concentrates in the early 1970s, significant improvements in quality of life and life expectancy of persons with haemophilia (PWH) were realized. Unfortunately, as a result of transmission of HIV and hepatitis C virus (HCV) by contaminated concentrates in the 1980s, many of these gains were lost. Now with four decades of PWH unexposed to contaminated factor products and current treatments capable of suppressing and eliminating HIV and HCV, respectively, the survival rate is once again increasing. In addition to the usual comorbidities associated with advanced age in the general population, several specific issues occur in patients with bleeding disorders. This manuscript explores the incidence and management of the comorbidities of the ageing PWH with a focus on cardiovascular disease and osteoporosis.

Physical activity levels in men with Haemophilia—A single centre UK survey

Historically persons with haemophilia (PWH) were not encouraged to participate in exercise due to the risk of bleeding and the lack of factor products available. This has now changed, and the availability of safe products allows PWH to be active and participate in sports. Studies have found that exercise has a positive effect on pain, joint health and movement with PWH. To record the amount and types of physical activity undertaken by a haemophilia population at a single treatment centre. An observational cross-sectional study to assess physical activity and quality of life of all registered patients over the age of 18 at the Oxford Haemophilia and Thrombosis Centre. Participants were posted questionnaires including the International Physical activity Questionnaire (IPAQ), Haemophilia Activity List (HAL), EQ-5D-5L and asked to list their physical activities. A total of 256 questionnaires were sent, with a 40% response rate for severe and 28% for mild patients. 85% met the UK physical activity guidelines. Sedentary behaviour for an average weekday was 6.4hours, and weekends were 5.3hours. Joint disease and severity type influenced the amount of activity undertaken, together with values for HAL and EQ-5D-5L. Twenty two types of activities were listed. It is encouraging to see the amount of physical activity PWH participate in, however, time spent in a sedentary state needs monitoring. PWH want to be active and the challenge for caregivers is to find activities they can do and strategies to maintain participation.

Health-Related Quality of Life, Treatment Satisfaction and Adherence Outcomes of Haemophilia Patients Living in a German Rural Region

In the context of the 'Mobile Haemophilia Outpatient Care (MHOC)' project we aimed to gather insights into the health-related quality of life (HRQoL), treatment satisfaction (TS) and adherence of persons with haemophilia (PWHs) who get treated at the Saarland University Hospital Haemophilia Treatment Centre (HTC). PWHs were visited at home at least twice (baseline, follow-up) by trained medical staff. Individual interviews were performed to measure patients' HRQoL and TS with validated questionnaires (Haem-A-QoL/Haemo-QoL and Hemo-SatA/Hemo-SatP). Socio-demographic and clinical data were collected. In total, 79 PWHs were enrolled; 56 adults with a mean age of 37.4 ± 16.4 years (17-78) and 23 children [mean age of 9.8 ± 4.2 years (3-16)]. In total, 62% were severely affected; 48.1% received prophylaxis. Patients reported good HRQoL (adults: 23.1 ± 17.1; kids: 24.3 ± 11.1). Patients (M = 11.2 ± 9.5) and parents (M = 14.3 ± 7.4) were very satisfied with their provided treatment. The majority of study participants were evaluated to have a good treatment adherence. After 1-year follow-up of the MHOC, a significant improvement in HRQoL was seen in adults (p < 0.033) and in proxy ratings of parents (p < 0.0001); TS remained high with no change by MHOC intervention. Patients reported good HRQoL and TS. Most of them were evaluated as having a good treatment adherence. After implementation of the MHOC, adult patients reported a better HRQoL. Such a mobile medical care service is considered beneficial for patients, especially with limited access to a HTC.

Guidelines for the prophylaxis of haemophilia A and B: new horizons and ambitions.

Guidelines for the prophylaxis of haemophilia A and B: new horizons and ambitions.

Movement behaviour patterns in adults with haemophilia.

Background:Joint bleeds are the hallmark of haemophilia, and can lead to disabling haemophilic arthropathy. Consequently, the movement behaviour of adults with haemophilia differs from that of healthy adults. It seems unlikely that a single outcome is able to reflect all relevant information regarding movement behaviour. The aim of the current study was to identify patterns of movement behaviour within persons with haemophilia (PWH) and compare clinical characteristics between patterns of movement behaviour.Methods:A total of 105 PWH [70% severe haemophilia; median age 43 years (30.0–54.0)] were included in the study. Hierarchical cluster analysis was used to identify patterns of movement behaviour. Clustering variables included seven parameters of movement behaviour: sitting, standing, walking, biking, running, frequency of active bouts and length of active bouts. Clinical characteristics included age, severity of haemophilia, joint health, physical functioning and pain. Clinical characteristics were compared between identified clusters by Kruskall–Wallis test. Movement behaviour was assessed with the Activ8 accelerometer, joint health was assessed on the Haemophilia Joint Health Score, physical functioning on the Haemophilia Activity List and the 40 m self-paced walk test and pain on the Numerical Pain Rating Score.Results:Cluster analysis identified three clusters, which were defined as: ‘sedentary’ (57%), ‘bikers and runners’ (22%) and ‘walkers’ (20%). The ‘bikers and runners’ showed better joint health and experienced fewer limitations in activities than the ‘walkers’ and the ‘sedentary’. The ‘walkers’ perceived fewer limitations in activities than the ‘sedentary’, with comparable joint health. We did not identify differences in pain, walking speed and age between the clusters.Conclusions:We identified three patterns of movement behaviour. The majority of PWH was identified as sedentary, whereas less sitting and regular walking during the day seemed to be more beneficial.

Pharmacoeconomic Analysis of Ideal Vs. Actual Body Weight-Based Treatment for Adult Persons with Hemophilia Α

Introduction: Clotting factor replacement therapy in the management of persons with hemophilia A (PwHA) is typically dosed using the following weight-based formula: Factor VIII (FVIII) Dose = Body weight (BW) in kg X desired FVIII increase (%) 2 This equation is based upon a FVIII in vivo recovery (IVR) of 2, which assumes that each FVIII unit per kg of BW infused will increase the circulating FVIII concentration by 2%. There have been a few studies demonstrating that IVR increases with increasing BW. A pharmacokinetic study performed using recombinant FVIII concentrate for pediatric PwHA &lt;6 years of age found that rising body mass index (BMI) resulted in a linear increase in IVR [Blanchette VS, et al. J Thromb Haemost 2008; 6: 1319-26]. Using data from eight pharmacokinetic clinical trials evaluating three recombinant FVIII concentrates in adult PwHA, Henrard et al. demonstrated that the IVR for an adult cohort consisting of 201 PwHA was 2.16. However, when these patients were stratified based on BMI: &lt;20.3 kg/m2, between 20.3 and 29.5 kg/m2, and &gt;29.6 kg/m2, each group had a significantly different and increasing IVR of 1.60, 2.14 and 2.70, respectively [Henrard S, et al. Haematologica 2013; 98: 1481-6]. As there are no guidelines for dosing of factor replacement therapy for obese PwHA, these studies suggest that ideal body weight (IBW) could be considered instead of actual body weight (ABW) in the dose calculations. With the prevalence of obesity in the hemophilia population now approaching that of the general population, dosing using IBW has potential economic ramifications [Wong TE, et al. Am J Prev Med 2011; 41: S369-75, Majumdar S, et al. Haemophilia 2011; 17: 717-8]. Objectives: 1) To estimate the prevalence of overweight and obese adult persons with hemophilia (PwH) in the state of Utah; 2) To estimate the cost savings for annual prophylactic clotting factor prescriptions if they were to be written using IBW vs. ABW for adult PwHA that are obese in the state of Utah. Methods: Adult PwH (≥18 years of age) who have been seen at least once in the past 3 years (January 1, 2016 to December 31, 2018) were identified from the Utah Center for Bleeding &amp; Clotting Disorders Registry. The following information was collected: Demographics; type of hemophilia; severity of hemophilia; height; weight; BMI. If BMI was not available, this was calculated based on the following equation, BMI = kilograms/meters2. Overweight was defined as a BMI 25 - 29.9 kg/m2. Obese was defined as a BMI ≥ 30 kg/m2. As there is limited data on the relationship between increasing BMI and IVR for factor IX concentrates, persons with hemophilia B were excluded in our cost savings analysis. For PwHA on clotting factor prophylaxis who were obese, the IBW was calculated using their height and the following equation for men: IBW (in kg) = 50 + 2.3 kg per each inch over 5 feet Using the prophylaxis schedule for each obese PwHA, an estimate of the annual cost was calculated using Wholesale Acquisition Cost and compared using both ABW and IBW. Results: A total of 87 adult PwH were seen with documented measurements of height and weight within the past 3 years. The patient characteristics are presented in Table 1. The mean and median age was 37.1 and 34 years, respectively (range: 19 - 75 years). The mean value for BMI was 28.1 and the median was 27.2 (range 17.3 - 46.0). Two patients had class III obesity (BMI ≥40 kg/m2). Almost two-thirds of adult PwH were overweight or obese (58/87; 65.5%). The prevalence of overweight and obese adult PwH in Utah based on age and severity of disease is shown in Figure 1. The estimated annual cost for each of the 12 adult obese PwHA based on their ABW vs IBW is shown in Figure 2. The difference in the total annual cost of treatment for the 12 adult PwHA on prophylaxis factor replacement therapy would be reduced by a total of roughly $2,100,000 if IBW was used rather than ABW; an average savings of $175,000 per adult PwHA per year. Conclusion: The relatively high prevalence of overweight and obesity in the Utah hemophilic population is similar to what has been reported in other states across the United States. The use of IBW in dose calculations has significant economic ramifıcations. Further studies performing individualized pharmacokinetic analysis for PwHA using IBW dosing must be coupled with close clinical monitoring to ensure safety of this dosing strategy before it can be adopted into routine clinical practice. Disclosures Rodgers: Pfizer: Consultancy; Octapharma: Consultancy; Novartis: Consultancy; Sanofi: Consultancy; AstraZeneca: Consultancy.

Hypertension and cardiovascular diseases in Swedish persons with haemophilia — A longitudinal registry study

IntroductionData on the prevalence of hypertension and cardiovascular diseases (CVD) among persons with haemophilia (PWH) vary. Sweden has a long tradition of maintaining population-based data registries, and there is extensive follow-up of haemophilia patients due to the use of prophylaxis over decades. We evaluated the prevalence of these diseases among Swedish PWH compared to matched controls using a longitudinal study design. MethodsData were obtained from the National Patient Registry and linked to records of persons with haemophilia enrolled in the haemophilia centres. For each subject, five gender and age matched controls were identified. ResultsWe identified 193 (19.7%) diagnoses of hypertension in PWH born in 1978 or earlier over ≥30 years compared with 550 (11.2%) among controls. The median ages and interquartile ranges were 60.0 (42.8, 69.9) and 57.2 (42.6, 70.6) years. The hazard rate (HR) for hypertension, PWH vs. controls, was 2.1, 95% CI: [1.8; 2.5], p < 0.001. The findings were similar in subgroup analyses of patients with non-severe and severe haemophilia with or without HIV and/or viral hepatitis. Angina pectoris was diagnosed in 69 (4.8%) of patients censored at age 75 compared with 311 (4.3%) in controls, and myocardial ischemia in 84 (5.9%) compared with 442 (6.2%). As a cause of death, the HR for myocardial ischemia, comparing PWH and controls, was 0.58, 95% CI: [0.42, 0.80], p = 0.001. ConclusionOur data support an increased prevalence of hypertension among persons with haemophilia. The prevalence of CVD seems to be similar to that of controls, but with lower mortality.

Screening urinalysis demonstrates that haematuria is a frequent finding in persons with haemophilia treated at a paediatric haemophilia treatment centre.

Haematuria is a recognized complication of haemophilia A and B (HA, HB). Adult persons with haemophilia (PWH) have a higher prevalence of renal disease than the general population. There is limited literature investigating the prevalence of haematuria in paediatric PWH. Our paediatric haemophilia treatment centre (HTC) had previously used quality improvement methods to increase the frequency of screening urinalyses at annual comprehensive visits. We retrospectively reviewed the data collected to determine the prevalence of haematuria and explore for associations in those with haematuria. Retrospective chart review to identify the frequency of haematuria on screening urinalysis in all male PWH ≥2years old. Haematuria was defined as ≥3 red blood cells (RBCs) per high power field. Univariate logistic regression was performed to evaluate for associations with haematuria. A total of 93 patients met eligibility criteria. Sixty-seven with HA (11 mild, 17 moderate, 39 severe) and 26 with HB (three mild, 16 moderate, seven severe). Forty-two of ninety-three (45%) patients were identified as having haematuria (median RBCs 7, mean RBCs 332). Of those with haematuria, 76% were identified by screening UA, as opposed to clinical symptoms, and 52% had recurrent haematuria. Older age and HA were associated with an increased likelihood of haematuria. Our study demonstrated that the prevalence of haematuria was high in PWH treated at our paediatric HTC. Future investigation is needed to determine the population-wide prevalence of haematuria in paediatric PWH and its impact on renal function.

Healthcare professionals in the 'tainted blood' era in Canada: Their forgotten emotions.

During the 1970s and early 1980s, Canada's comprehensive care haemophilic programs were established. Newer therapies led to a rapid increase in quality of life and expected life span for persons with haemophilia (PWH). The outlook was bright. However, beginning in 1982, the appearance of HIV/AIDS transmitted by treatment products led to the 'tainted blood' era with its devastating impact on PWH, recently highlighted in the Canadian Broadcasting Corporation mini-series 'Unspeakable'. What has received less notice is how the healthcare professionals (HCP) managing these patients then were affected. To report the emotional effects of that era on HCPs. In developing an oral history of haemophilic care in Canada we have interviewed 76 HCPs, the majority of whom had worked in haemophilic clinics during that era. During each interview, we asked the interviewee to reflect on what this did to haemophilic care and to him/herself. The interview responses were analysed. HCPs have been markedly affected by the events of the 1980s with feelings that persist more than 30 years later. Most related to the loss of so many of their patients and the inability to alter the rapidly changing course of events at the time. The 'tainted blood' era had persistent strong emotional effects on HCPs. They were helpless to stop or to mitigate the devastating epidemics. Wellness support programs were less well developed then. While the focus is in the Canadian context, we suggest that a parallel can be drawn within haemophilic communities in other countries.

PS1109 DENTAL HEALTH STATUS IN PATIENTS WITH HEMOPHILIA. SINGLE CENTER EXPERIENCE IN ROMANIA

Background:Shortage of replacement therapy in haemophilia is responsible for the devastating consequences of uncontrolled bleeds, with unfavourable impact on the quality of life, strongly dependent on oro‐dental health.Aims:The objective of our study was to analyse the dental status in persons with haemophilia (PwH) in our treatment conditions, characterised by the introduction of on demand replacement in 1997 and of prophylaxis in 2014‐2015.Methods:This descriptive non‐interventional cross‐sectional study was conducted on 47 PwH (12 children, 35 adults), all with severe form of disease and on a control matched group of 47 persons. For each PwH were recorded laboratory data and history of replacement therapy. Oral health status evaluation was performed according to the criteria suggested by World Health Organization (WHO).Results:We assessed a very bad dental status in PwH with very high values for the majority of the parameters. In haemophilic children comparable to matched control group there were significant differences regarding the D index and PL index (p = 0.04, p = 0.01). Concerning the domain of decayed teeth in children we observed the existence of an age correlation (r = 0.47/0.81), unfortunately with a lowering appeal for dental care in children with haemophilia, the F index (0.2 ± 0.4) being decreased compared to the children from control group (2.2 ± 2.2), with significant difference (p = 0.003). The dental indexes in adult haemophiliacs were found high, significantly higher in the field of D and F than those belonging to the control group. F index was found significantly higher in the control group than in PwH, proving the low addressability for dental care in haemophiliacs. All these results, with the exception of Missing teeth and DMFT index (r = 0.63/r = 0.65), were not correlated with the age. Adult PwH, with mean age of 34.8 ± 9.81 years, had a dismal dental profile, only 7/35 had a complete denture, 7/35 missing 25%, and 3/35 missing more than 50% of their teeth.Summary/Conclusion:Lack of access to treatment or a low consumption, especially in young age, can influence and have a decisive impact on oral health status in PwH. Our results highlight the importance of an accessible dental care for this vulnerable group of patients in the frame of a comprehensive haemophilia care, including preventive dental treatment and an adequate replacement therapy.

The impact of haemophilia on the social status and the health-related quality of life in adult Lebanese persons with haemophilia.

Health-related quality of life (HRQoL) studies are increasingly needed to prevent and improve the medical care of persons with haemophilia (PWH). We assessed the impact of haemophilia on HRQoL and social status of adult Lebanese PWH compared to a reference population. In this case-control study, 60 severe and moderate PWH were compared to 112 healthy controls. Detailed socio-demographic data and disease characteristics were collected, and HRQoL was assessed using the SF-36 questionnaire. Age, body mass index and the percentage of married people were similar in PWH and controls. A greater proportion of controls attained a higher educational level than cases (88.4% vs 59.3%, respectively, P<0.001). PWH were more likely to have a job requiring physical activity than controls (55.9% vs 31.4%) and more likely to be unemployed (10.2% vs 1.0%), whereas more controls had higher socio-economic jobs (10.5% vs 1.7%). PWH had significantly (P<0.001) worse scores in all SF-36 domains except for energy/fatigue. Affected targeted joints (2.7±1.5) and monthly bleeding frequency (2.9±2.4) were inversely correlated with almost all SF-36 domains. Only 26.7% of PWH walk normally, and walking abnormalities were inversely correlated with all SF-36 domains except role-emotional and emotional well-being. As compared with controls, the majority of Lebanese PWH has difficulties in social integration, has severe physical limitations and psychological impairments.

Health Status of Persons with Hemophilia: A Pilot Survey from a Resource-Constrained Country.

Background:Most resource-poor countries are yet to develop standard hemophilia treatment center (HTC) despite improved outcome of health status of persons with hemophilia (PWH).Aim:This study aimed to evaluate the health status of PWH in Nigeria.Methodology:In this descriptive, cross-sectional study, modified prevalidated and pretested questionnaire (National health and Nutrition examination survey (NHANES) 2013 Health Status questionnaire (HSQ)) was consecutively administered to consenting PWH (pediatric and adult) attending the 2018 Annual General Meeting of the Haemophilia Foundation of Nigeria. The study's measurable outcome variables were calculated health status and its determinants. Association between the outcome variables and clinical characteristics of PWH was done using SPSS software version 22, and P < 0.05 was considered statistically significant.Results:Of the 36 PWH who participated in the survey, 50% had good health status, 38.9% had poor health status, while only 11.1% had excellent health status. A majority (88.9%) had access to HTC with <6 consultations in the past year. Nearly 47.2% were hospitalized for disease-related problem in the past year. There was nonsignificant difference between health status and disease type (P = 0.751) and severity (P = 0.086), treatment plan (0.496), type of treatment facility (P = 0.152), and access to a doctor (P = 0.67).Conclusion:Several PWH in resource-poor settings still suffer serious morbidity that impacts negatively on their health status. More robust (multicenter) research is needed to ascertain the true picture of health status of PWH in resource-poor countries.