[Educational needs of parents of hemophiliac children: An approach to comprehensive care]. / Necesidades educativas de padres de niños hemofílicos: Una aproximación hacia el cuidado integral.

INTRODUCTION: In Chile, hemophilia was incorporated into the System of Explicit Health Guarantees (GES), which ensures access to treatment and financial protection for these patients. To support patients and their families, educational programs have been proposed that focus on managing possible complications of the pathology, first aid, and prophylaxis, however, there are no educational instances focused on the needs of the patients. OBJECTIVE: To know the educational needs of parents with hemophilic chil dren and adolescents regarding contents, people, place, methodology, and stage of the illness. Sub jects and Method: Descriptive qualitative study of 15 parents with hemophilic children in outpatient care. For the data collection, we used a semi-structured interview with five open questions, aimed at the search for educational needs such as what (contents), how (methodology), when (moment), who (person), and where (place) is education needed. For data analysis, were used the Berelson's content analysis technique. To guarantee the scientific validity of the qualitative results, the methodological rigor criteria of Guba and Lincoln were used. RESULTS: The most frequent educational needs reported by parents include content such as venipuncture training, injury prevention, pathophysiological as pects of the disease, among others; with methodology developed in group workshops and guided by a peer; in a comfortable and familiar place; in three stages of the disease's development (diagnosis, blee ding events, and development of autonomous activities), and provided by professionals and peers. CONCLUSION: Knowledge of educational needs is the basis for the creation of an educational program that guides the comprehensive care of hemophilic children and their parents.

Real-World Utilisation and Bleed Rates in Patients with Haemophilia B Who Switched to Recombinant Factor IX Fusion Protein (rIX-FP): A Retrospective International Analysis.

INTRODUCTION: Despite the well-documented benefits of prophylaxis, treatment burden is still a barrier to adherence in patients with haemophilia. An extended half-life fusion protein linking recombinant FIX (rFIX) with human albumin (rIX-FP) has been developed for the treatment of patients with haemophilia B and is indicated for dosing up to every 14 days. This analysis evaluated real-world outcomes in patients switching to rIX-FP from the previous FIX product in Italy, Belgium and the UK. METHODS: Anonymised chart data were collected from the pre-existing medical records of patients with haemophilia B between May and September 2018. Patients were included in the analysis if they had been treated with rIX-FP for ≥ 8 weeks. Data were compared between rIX-FP and the patient's prior FIX product. RESULTS: Twenty-three HTCs from Italy (n = 13), Belgium (n = 3) and the UK (n = 7) provided data for 84 male patients, 92.8% of which had severe haemophilia B. The majority of patients were previously on prophylactic regimens with their prior FIX product (Italy, 44/49; Belgium, 7/10; UK, 22/25). The switch to prophylaxis with rIX-FP led to reductions in mean annualised bleeding rate of 94.3% in Italy, 93.9% in Belgium and 67.7% in the UK compared with prior FIX prophylaxis. Overall, 41% of patients experienced zero spontaneous bleeds prior to switching, compared with 88% following the switch to rIX-FP. The majority of patients had a reduction in dosing frequency following the switch, with 98.6% of patients dosing once weekly or less frequently compared with 9.6% of patients dosing at this frequency with their prior FIX. Mean weekly FIX consumption was reduced compared with prior FIX prophylaxis. CONCLUSION: This retrospective review of real-world evidence demonstrated that switching to rIX-FP from prior FIX was associated with improved haemostatic efficacy and reduced factor consumption in patients with haemophilia B from Italy, Belgium and the UK.

While clinical trials provide robust evidence as to the effectiveness and safety of a new drug, they are tightly controlled and so may not reflect some of the issues that may be discovered in clinical practice. Therefore, real-world analyses are important to determine how a product performs in patients in everyday settings. This study looked at the use of an extended half-life fusion protein linking recombinant FIX (rFIX) with human albumin (rIX-FP), which was designed to allow longer dosing intervals, in patients with haemophilia B in Italy, Belgium and the UK, and compared this with the patients' previous FIX product. Anonymous patient chart data were collected from participating centres and analysed in terms of bleeding rate, factor usage and dosing frequency for rIX-FP and previous FIX product. The results showed that after switching to rIX-FP, patients experienced lower bleeding rates, lower factor usage and less frequent dosing regimens compared with their previous FIX product. This is the first analysis to assess the real-world clinical benefits of switching to prophylaxis with rIX-FP from a prior FIX product in Italy, Belgium and the UK. This study further strengthens the results seen in clinical trials with rIX-FP, confirming that the effective bleeding prevention demonstrated in clinical trials is consistent with that seen in patients in real-world clinical practice.

Effects of exercise in people with haemophilia: An umbrella review of systematic reviews and meta-analyses.

INTRODUCTION: There is considerable evidence to indicate that exercise can have a positive impact on the treatment of people with haemophilia (PWH). However, there is a requirement for in-depth and comprehensive studies. AIM: This study aimed to analyse the evidence regarding the effects of exercise in PWH through an umbrella review of existing systematic reviews and meta-analyses. The secondary objective was to analyse the quality of the evidence. METHODS: This umbrella review followed the PRISMA guidelines and was documented in the PROSPERO registry (CRD42019140785). We searched the PubMed, Web of Science, SPORTDiscus, Scopus, CINAHL and Cochrane Library databases. The methodological quality of the systematic reviews was assessed using AMSTAR 2. RESULTS: Out of a total of 1030 systematic reviews, 10 fulfilled the criteria. Only one study was classified as high quality, and half of the selected studies were classified as low or critically low quality according to AMSTAR 2. Furthermore, most reviews investigated the effects of strength training and aquatic training, with positive results associated with low adverse events. Range of motion, strength and pain were the most investigated variables. All reviews showed overlapping studies. CONCLUSION: Exercise is an effective way to treat haemophilia and has a low incidence of related adverse events. However, caution is needed in the interpretation of the results due to half of the selected reviews showed low or critically low quality and only one have high quality.

Nutritional status of children and adolescents with haemophilia in Basra, Iraq.

INTRODUCTION: Patients with haemophilia are at increased risk of being overweight or obese, which in turn may have a profound effect on morbidity and quality of life. AIMS: To assess the nutritional status of paediatric patients with haemophilia and identify possible risk factors that may adversely affect their nutritional status. METHODS: A case-control study was performed on 63 haemophilia patients and 135 control subjects aged 5-18 years. For all participants, weight, height and body mass index Z (BMIZ) score were assessed. Physical activity (PA) was assessed using the International Physical Activity Questionnaire and the Children's Physical Activity Questionnaire for participants ≥15 years and 5-14 years old, respectively. RESULTS: The frequency of overweight and obesity was 36.29% among the control group compared with 23.81% among patients, while thinness was higher in patients with haemophilia (19.05%) compared with 9.63% in the control group, P = .042. Low PA was reported in 22.73% of haemophilia patients aged 5-14 years compared with 2.06% in the control group, P < .001. However, no difference in PA was reported among participants aged ≥15 years. There were no significant differences in the frequency of nutritional problems among patients with respect to age, type of haemophilia, disease severity and hepatitis C seropositivity. Regression analysis revealed a negative association between paternal educational level and high BMIZ in patients ≥15 years, P = .028. CONCLUSIONS: Paediatric patients seem to have lower BMIZ than the control group. In addition, most of the studied factors were not found to predict either high or low BMIZ among studied patients.

Physical activity and its related factors in Japanese people with haemophilia.

INTRODUCTION: In the general population, benefits of physical activity (PA) include improvement of physical function, prevention of lifestyle diseases and improvement of bone mineral content and quality of life. PA is recommended for patients with haemophilia (PwH), especially for those receiving advanced haemostatic treatment. We hypothesised many PwH engage in insufficient PA. AIM: This study aimed to clarify PA levels and the associated factors in Japanese PwH. METHODS: Physical activity was assessed using the International Physical Activity Questionnaire short version, and basic data, activities of daily living (ADLs) and self-efficacy were also collected. RESULTS: A total of 106 questionnaires were completed. The average age of participant was 40.8 years. The median PA was 693.0 metabolic equivalent-min/wk. More than half of the participants (59.4%) were classified into the low activity group. PA showed a significant inverse correlation with age (P = 0.022) and a positive correlation with self-efficacy (P = 0.018). However, PA did not show a significant relationship with haemophilic severity, prophylactic treatment, annual intra-articular bleeding frequency, body mass index and ADL. In PwH receiving guidance in sports, such as activities that are safe to participate in or performing prophylaxis prior to a physical activity, self-efficacy was significantly higher (P = 0.033), ADL was better (P < 0.001), and mean age was younger (P = 0.01) than in those not receiving guidance in sports. CONCLUSION: As for PA level, 60% of the subjects showed low activity. To promote PA in PwH, improvement of self-efficacy and appropriate guidance may be necessary.

Safety of recombinant coagulation factors in treating hemophilia.

INTRODUCTION: During the last decade, new FVIII/IX concentrates have been developed for the treatment of patients affected by hemophilia A/B. Significant progress has been achieved regarding their half-life, but the old issue of immunogenicity and new concerns about safety need to be addressed. AREAS COVERED: After the implementation of virucidal methods, both plasma-derived and recombinant clotting factor concentrates achieved a very safe profile. The development of anti-FVIII antibodies is the major adverse event of replacement therapy with both FVIII concentrates. Furthermore, the new extended half-life concentrates, protein fused or pegylated, raised some concerns about their side effects. EXPERT OPINION: The treatment of hemophilia A with inhibitors by induction of immunotolerance and using by-passing concentrates, improved the quality of life of patients but did not allow them to have a life expectancy like that of patients without inhibitors. The new humanized monoclonal antibody (MAb) ACE910, mimicking FVIII function, seems to be able to reduce the bleedings of hemophilia A patients with inhibitors. The post-marketing surveillance will clarify if the adverse events observed during the phase III clinical trials and compassionate use were due to the association with a Prothrombin activated complex concentrate or to the prothrombotic effect of the drug itself.

Joint Mobility and Physical Function of Danish Hemophilia Patients: A Three-Wave Panel Study Spanning 24 Years.

BACKGROUND: The positive effects of factor treatment of hemophilia are well established, but the long-term outcomes are not well documented. This panel study evaluated changes in bleeding frequency, joint mobility, physical function, and symptoms in Danish patients with moderate to severe hemophilia A or B over 24 years. METHODS: Three anonymous surveys were conducted in 1988, 2001, and 2012 targeting Danish patients with moderate to severe hemophilia, and the study participants, respectively, were 128, 156, and 164 male patients with hemophilia (PWH). The number of bleeding episodes, the use of factor concentrate, comorbidities, joint mobility, physical function, and symptoms were evaluated by means of self-reporting. Trends over time were analyzed using ordinal and multinomial logistic-regression models controlling for age group. RESULTS: The proportion of PWH in the oldest age group (55-88 years) increased from 4% in 1988 to 18% in 2012. In 1988, a high risk of bleeding episodes was primarily found in the age group of 16-34 years. In 2012, a high risk was primarily found in the age group of 35-54 years. Joint mobility and physical function increased significantly from 1988 to 2012 but showed a noticeable decrement in the older age groups, even in 2012. Pain in the extremities, anxiety, and depression decreased significantly, but back pain increased. No significant changes were found for 7 other symptoms. CONCLUSIONS: Significant improvements in joint mobility and physical function have occurred over the last 24 years, but PWH > 35 years still experience a decline in these areas with age. This decline underscores the importance of life-long treatment and continuous rehabilitation of PWH.

Impact of Exercise/Sport on Well-being in Congenital Bleeding Disorders.

Physical activity provides many benefits in patients with congenital bleeding disorders. Patients with hemophilia are encouraged to participate in exercise and sports, especially those patients receiving prophylaxis. Several publications and guidelines have explored this issue in hemophilia patients, evaluating in particular the impact of physical activity on patients' well-being and quality of life. The other rare congenital bleeding disorders are less studied; they are heterogeneous in terms of clinical bleeding phenotype, incidence of hemarthrosis, and arthropathy. Furthermore, prophylaxis in these patients is less common than in hemophilia patients, which must be considered when choosing the type of physical and sporting activity. In this review, the authors have analyzed the literature focusing their attention on those rare coagulation disorders that may be complicated by arthropathy and the role of exercise and sports in this context.

Impact of Exercise on Hemophilia.

Sports and strenuous exercise have traditionally been discouraged for people with hemophilia (PWH) because of the perceived risk of bleeding. In this review, studies investigating the pros and cons of exercise are presented, and although most studies are of low validity, the randomized trials that do exist tell us that PWH benefit from exercise in terms of improved muscular function, endurance, and quality of life and that increased bleeding does not seem to be an issue. The authors also review the studies that have analyzed the current physical status of PWH compared with the general population in different countries. Finally, they review the current knowledge on the effect of exercise on specific coagulation factors as well as on global coagulation and demonstrate that exercise increases factor VIII levels in healthy persons, all persons with hemophilia B (HB) and in persons with mild and moderate hemophilia A (HA). Further, the authors did not find any evidence that the global coagulation capacity, measured with thrombin generation or thromboelastographic methods, increases after exercise in severe HA or HB.

Low bone mineral density and associated factors in patients with haemophilia in Colombia.

INTRODUCTION: Patients with haemophilia may have lower levels of bone mineral density (BMD) compared with the general population. Moreover, haemophilic patients have increased risk factors for low bone mineral density (LBMD) such as arthropathy and resulting immobility, increasing their risk for osteoporosis and fractures. AIM: To assess the prevalence of LBMD and associated risk factors among a group of Colombian haemophilic patients. METHODS: In this case-control study, 90 patients with haemophilia A and B, over the age of five, were recruited. Controls were healthy participants matched by age, gender, body mass index (BMI), socioeconomic status, and race. All participants underwent dual energy X-ray absorptiometry (DXA) and the Global Physical Activity Questionnaire. Blood tests were collected to evaluate LBMD determinants in cases. RESULTS: BMD was lower in cases than in the control group. BMD of femoral necks was 0.907 g/cm2 in cases vs. 1.020 g/cm2 in controls (P = .019), and BMD of hips 0.930 g/cm2 in cases vs. 1030 g/cm2 in controls (P = .019). The greater the severity of haemophilia, the lower BMD in spine, femoral neck, and hips. Elevated C-protein levels were found in 44.1% of patients with LBMD and 14.8% with normal BMD (P = .003). The study found an adjusted prevalence ratio of 2.11, indicating that haemophilic patients are two times more likely to have LBMD (CI95% = 1.43-3.11 P < .001). CONCLUSION: Results from the present study showed that haemophilia was associated with a higher frequency of LBMD. Severity of haemophilia, haemophilic arthropathy, and elevated C-reactive protein levels was directly associated with LBMD.

Methodologies for data collection in congenital haemophilia with inhibitors (CHwI): critical assessment of the literature and lessons learned from recombinant factor VIIa.

AIMS: To systematically review the effectiveness of on-demand treatment with recombinant coagulation factor VIIa (rFVIIa) in congenital haemophilia with inhibitors and, if feasible, perform a meta-analysis of the data. MATERIALS AND METHODS: Publications from Embase® , MEDLINE® , MEDLINE® In-Process and the Cochrane Central Register of Controlled Trials were searched. Selected publications were reviewed for inclusion by two independent expert reviewers. Discrepancies were reconciled by a third independent reviewer. Data from selected studies were extracted using a predefined grid to ensure uniform and comparable results were captured. RESULTS: A systematic search (cut-off date of 2 May 2016) identified 20 studies (13 observational; seven randomized controlled trials). All studies were of sufficient quality to include in this analysis and comprised 1221 participants, with 5981 bleeds in 746 individuals treated with rFVIIa. Haemostatic overall effectiveness of the individual studies identified ranged from 68% to 100% at ≤12 hours, 86% to 96% at 13-24 hours and 76% to 99% at 24-48 hours with rFVIIa <100 µg/kg, with similar rates reported for the ≥250 µg/kg dose. However, heterogeneity between the studies precluded pooling of results. CONCLUSIONS: Data from the individual studies confirmed that rFVIIa is an effective therapy for the on-demand treatment of bleeds in congenital haemophilia with inhibitors. However, the high levels of heterogeneity between studies precluded pooling of results for a valid, reliable or precise summary measure. There remains a need to implement standardized clinical definitions and measurements for the effectiveness and safety of haemophilia therapies in future clinical trials.

Muscle function deterioration in patients with haemophilia: Prospective experience from Costa Rica.

INTRODUCTION: In haemophilia, recurrent joint bleeds are responsible for the development of chronic joint damage, because blood induces biochemical changes in joint structures. Joint degeneration is a long process, and structural damage is often preceded by joint dysfunction, which is represented by quantitative and qualitative changes in the contraction pattern of muscles around the joints. Muscle function in patients with haemophilia is still poorly investigated. AIM: The aim of this 2-year prospective study was to assess the changes in muscle function of lower limbs in a group of patients affected with haemophilia in San José, Costa Rica. METHODS: Muscle function of lower limbs was assessed by means of surface electromyography (sEMG) accomplished at study enrolment and after 2 years of follow-up. Gluteus medius, vastus medialis, biceps femoris, gastrocnemius and tibialis anterior were examined. All patients underwent concurrent clinical examination using Haemophilia Joint Health Score (HJHS). RESULTS: Sixty patients aged 2-43 years with severe haemophilia underwent clinical and sEMG evaluation. Thirty-two patients (53%) had target joints. sEMG parameters were altered in all patients and were not correlated to the presence of target joints and/or an abnormal HJHS. Muscle function deterioration was observed after 2 years of follow-up despite an unmodified HJHS. CONCLUSIONS: Muscle function of lower limbs as detected by means of sEMG was impaired in patients with haemophilia irrespective of the presence of overt joint damage. sEMG is a simple and sensitive assessment tool able to detect muscle dysfunction and so favouring the implementation of early rehabilitation therapy.

Evaluation of bone mineral density (BMD) and indicators of bone turnover in patients with hemophilia.

A decrease in bone mass is observed in hemophilic patients. The aim of this study was to evaluate bone mineral density (BMD), parathyroid hormone (PTH), 25-hydroxy vitamin D (vitamin D), and a bone formation and resorption marker, procollagen type I N-terminal propeptide (PINP) and urinary N-terminal telopeptide (uNTX) respectively, in hemophilic patients and healthy controls. Laboratory parameters related to the pathogenesis of bone loss such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were also evaluated. Thirty-five men over 18 years of age, with severe hemophilia (A and B) and receiving secondary prophylaxis, were included in the study. The same number of age-, sex-, and ethnicity-matched healthy controls were evaluated. Anthropometric, biochemical, and hormonal parameters were determined in both groups. No significant difference in anthropometric parameters was found between the two groups. The BMD was low in 34% of hemophilic patients. Vitamin D, calcium, and free testosterone levels were significantly lower (p < 0.001, p = 0.011, p < 0.001, respectively), while PTH, PINP, and activated partial thromboplastin time (aPTT) levels were significantly higher (p < 0.014, p = 0.043, p < 0.001, respectively), in hemophilic patients compared to controls. There was no significant difference between the two groups in NLR, PLR, phosphorus, thyroid-stimulating hormone, and uNTX level. The reduction of bone mass in hemophilic patients may be evaluated using the markers of bone formation and resorption, enabling early detection and timely treatment.

Reliability and clinical features associated with the IPSG MRI tibiotalar and subtalar joint scores in children, adolescents and young adults with haemophilia.

OBJECTIVES: To assess the reliability of the IPSG MRI scale for tibiotalar (TTJ) and subtalar joint (STJ) changes in young haemophilic patients, correlating MRI findings with functional scores and 3D-rearfoot kinematics. METHODS: A total of 37 haemophilic patients underwent bilateral MRI of the footankle, clinical evaluation and quantitative assessment of their 3D-rearfoot kinematics during walking. TTJ and STJ soft tissues were assessed twice along with osteochondral changes by two radiologists using the IPSG MRI scale. Inter- and intra-observer reproducibility of MRI scoring were tested by means of kappa statistics. Correlational analyses were performed between MRI findings and the Haemophilia Joint Health Score 2.1 (HJHS) and 3D-rearfoot kinematic data. RESULTS: The intra-reader reliability of MRI scoring was good to excellent (Kappa: 0.62-1), whereas the inter-reader reliability was moderate to good (Kappa: 0.54-0.79). Weak yet significant correlations were found between the frontal plane rearfoot range of motion (ROM) during loading response of gait and STJ score, as well as between frontal plane rearfoot ROM during the terminal stance phase and the rearfoot osteochondral lesions. CONCLUSION: The IPSG score appears applicable to not only the TTJ but also the STJ. Contrary to TTJ lesions, those of the STJ do not correlate with the HJHS but do with 3D-rearfoot kinematic data.

Somatosensory profile of patients with haemophilia.

INTRODUCTION: Patients with haemophilia (PwH) suffer from an enhanced pain sensitivity due to repetitive joint bleedings. A comprehensive, quantitative examination of the somatosensory system has not been performed in this population to date. MATERIAL AND METHODS: Thirty patients with moderate or severe haemophilia A or B and 30 healthy controls were examined by means of Quantitative Sensory Testing to assess the function of the somatosensory system. Detection (DT) and pain thresholds (PT) were determined, amounting to a total of 13 parameters. Both knee joints and the hand as reference were examined in order to assess both joint-specific as well as general changes in the somatosensory profile. RESULTS: Analysing DT and PT, a significant main effect was found for group × stimulus interaction (P ≤ .001). Post hoc tests revealed significant differences in DT between PwH and controls for thermal stimuli across both knees (cold DT: P < .001; warm DT: P < .01) and the hand (cold DT: P < .01; warm DT: P < .05). Mechanical DT was increased in PwH at both knee joints (left knee: P ≤ .05; right knee: P ≤ .01). Furthermore, pressure PT was decreased in PwH at both knees (P ≤ .001). CONCLUSION: Haemophilic arthropathy leads to alterations of the somatosensory profile in PwH. Our results reveal initial evidence of a combination of peripheral sensitization, indicated by decreased pressure PT and mechanical DT at the knee joints, as well as general changes of the somatosensory system, shown by reduced thermal DT at affected sites and remote from these. Therefore, both mechanisms have to be considered regarding the pain management in PwH.

Economic Burden of Illness among Persons with Hemophilia B from HUGS Vb: Examining the Association of Severity and Treatment Regimens with Costs and Annual Bleed Rates.

OBJECTIVES: To determine US societal burden of illness, including direct and indirect costs and annual bleed rate (ABR), for persons with hemophilia B (HB), a rare and debilitating genetic disorder, and to examine associations of hemophilia severity and treatment regimens with costs and ABR. METHODS: From 2009 to 2014, the Hemophilia Utilization Group Studies Part Vb collected prospective data from 10 US hemophilia treatment centers. Participants with HB completed initial surveys on sociodemographic characteristics, clinical characteristics, and treatment patterns. During the 2-year follow-up, participants reported bleeding episodes, work absenteeism, and caregiver time quarterly. These data were used to calculate ABR and indirect costs. Direct costs were calculated using 1-year clinical chart records and 2-year dispensing records. RESULTS: Of the 148 participants, 112 with complete medical records and one or more follow-up survey were included. Total mean annual per-person costs were $85,852 (median $20,160) for mild/moderate HB, $198,733 (median $147,891) for severe HB, and $140,240 (median $63,617) for all participants without inhibitors (P < 0.0001). Mean ABR for participants with severe HB on prophylaxis (5.5 ± 7.9 bleeds/y) was almost half that of those treated episodically. Clotting factor and indirect costs accounted for 85% and 9% of total costs, respectively. Compared with episodic treatment, prophylaxis use was associated with 2.5-fold higher clotting factor costs (P < 0.01), low but significantly more missed parental workdays (P < 0.0001) and clinician (P < 0.001) or nursing visits (P < 0.0001), less part-time employment and unemployment, and lower hospitalizations costs (P = 0.17) and ABR (P < 0.0001). CONCLUSIONS: HB is associated with high economic burden, primarily because of clotting factor costs. Nevertheless, prophylaxis treatment leads to clinical benefits and may reduce other nonfactor costs.

Partnering to change the world for people with haemophilia: 7th Haemophilia Global Summit, Madrid, Spain 22-24 September 2016.

The 7th Haemophilia Global Summit was held in Madrid, Spain, in September 2016. With a programme designed, for the 6th consecutive year, by a Scientific Steering Committee of haemophilia experts, the aim of the summit was to share optimal management strategies for haemophilia at all life stages and to provide an opportunity for specialists from across the haemophilia multidisciplinary care team to engage in discussion and debate with leading international experts on current and future areas of research. Topics covered ranged from the optimisation of haemophilia management, emerging issues in clinical care, practical approaches and future perspectives, in addition to patient engagement and empowerment in modern haemophilia care.

Monitoring joint health in haemophilia: Factors associated with deterioration.

INTRODUCTION: Joint bleeds in patients with haemophilia may result in haemophilic arthropathy. Monitoring joint health is essential for identifying early signs of deterioration and allows timely adjustment of treatment. AIM: The aim was to describe changes in joint health over 5-10 years follow-up and identify factors associated with joint health deterioration in patients with haemophilia. METHODS: A post hoc analysis was performed from previous cohort studies in patients with moderate/severe haemophilia, ≥16 years. Joint health of ankles, knees and elbows was measured with the Haemophilia Joint Health Score (HJHS) from 2006-2008 (T0) to 2011-2016 (T1). Analyses were performed on patient level (ΔHJHS-total) and joint level (ΔHJHS-joint). Deterioration was defined as ΔHJHS-total ≥4 and ΔHJHS-joint ≥2. RESULTS: Sixty-two patients (median age 25, 73% severe haemophilia, median [interquartile range] 0.0 [0.0;2.0] joint bleeds between T0 to T1) were included. After median 8 years, HJHS-total deteriorated in 37% and HJHS-joint in 17%. Ankle joints (31%) showed deterioration more often than elbows (19%) and knees (3%). Deterioration of HJHS-total was only associated with severe haemophilia. Deterioration of HJHS-joint was weakly associated with a lower HJHS at baseline and more self-reported limitations in activities, and strongly with more joint bleeds between T0 and T1 and presence of synovitis. CONCLUSION: In 37% of patients with moderate/severe haemophilia and low joint bleeding rates, joint health deteriorated over 5-10 years. Ankle and elbow joints showed deterioration most frequently. Factors found in this study help to identify which joints need frequent monitoring in patients with haemophilia with access to early prophylaxis.

Adult males with haemophilia have a different macrovascular and microvascular endothelial function profile compared with healthy controls.

INTRODUCTION: Endothelial function has been identified as an independent predictor of cardiovascular risk in the general population. It is unclear if the haemophilia population has a different endothelial function profile compared to the healthy population. AIM: This prospective study aims to assess if there is a difference in endothelial function between haemophilia patients and healthy controls, and the impact of endothelial function on vascular outcomes in the haemophilia population. Baseline cardiovascular risk factors and endothelial function were presented. METHODS: Adult males with haemophilia A or B recruited from the British Columbia and Southern Alberta haemophilia treatment centres were matched to healthy male controls by age and cardiovascular risk factors. Macrovascular endothelial function was assessed by brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD), and microvascular endothelial function was assessed by hyperaemic velocity time integral (VTI). Multivariable linear regression was used to assess the association between haemophilia and endothelial function. RESULTS: A total of 81 patients with haemophilia and 243 controls were included. Patients with haemophilia had a similar FMD and NMD compared to controls, although haemophilia was associated with higher FMD on multivariable analysis. Haemophilia was associated with significantly lower VTI on univariate and multivariable analyses, regardless of haemophilia type and severity. CONCLUSIONS: Adult males with haemophilia appear to have lower microvascular endothelial function compared to healthy controls. Future studies to assess the impact of endothelial dysfunction on cardiovascular events in the haemophilia population are needed.