Clotting factor activity levels and bleeding risk in people with haemophilia playing sports.

BACKGROUND: Improved treatment options for people with haemophilia (PWH) have increased the possibilities for sports participation, but the risk of sports-induced bleeding (SIB) is still considered considerable by many. AIM: To assess sports associated injury- and bleeding risk in PWH and to assess clotting levels associated with safe sports participation. METHODS: Sports injuries and SIBs were prospectively collected for 12 months in PWH aged 6-49 without inhibitors playing sports at least once weekly. Injuries were compared according to factor levels, severity, joint health, sports risk category and sports intensity. Factor activity at the time of injury was estimated using a pharmacokinetic model. RESULTS: 125 participants aged 6-49 (41 children, 90% haemophilia A; 48% severe, 95% severe on prophylaxis) were included. Sports injuries were reported by 51 participants (41%). Most participants (62%) reported no bleeds at all and only 16% reported SIBs. SIBs were associated with factor levels at time of injury (OR: 0.93/%factor level (CI 0.88-0.99); p = .02), but not with haemophilia severity (OR: 0.62 (CI 0.20-1.89); p = .40), joint health, sports risk category or sports intensity. PWH with factor levels <10% during sports injury had a bleeding risk of 41% versus 20% in those with higher (>10%) factor levels. CONCLUSION: The results of this study emphasize the importance of clotting factor levels in prevention of bleeds. This information is vital for patient counselling and tailoring prophylactic treatment with clotting factors and non-replacement therapy.

Can motor proficiency testing predict sports injuries and sports-induced bleeds in people with haemophilia?

INTRODUCTION: Predicting the risk of sports injuries and sports-induced bleeds (SIBs) in people with haemophilia (PWH) may support clinical counselling. AIM: To assess the association between motor proficiency testing and sports injuries and SIBs and to identify a specific set of tests for predicting injury risk in PWH. METHODS: In a single centre, prospective study male PWH aged 6-49 playing sports ≥1x/week were tested for running speed and agility, balance, strength and endurance. Test results below -2Z were considered poor. Sports injuries and SIBs were collected for 12 months while 7 days of physical activity (PA) for each season was registered with accelerometers. Injury risk was analysed according to test results and type of physical activity (%time walking, cycling, running). Predictive values for sports injuries and SIBs were determined. RESULTS: Data from 125 PWH (mean [± SD] age: 25 [± 12], 90% haemophilia A; 48% severe, 95% on prophylaxis, median factor level: 2.5 [IQR 0-15]IU/dl) were included. Few participants (n = 19, 15%) had poor scores. Eighty-seven sports injuries and 26 SIBs were reported. Poor scoring participants reported 11/87 sports injuries and 5/26 SIBs. The current tests were poor predictors of sports injuries (Range PPV: 0%-40%), or SIBs (PPV: 0%-20%). PA type was not associated with season (activity seasonal p values > .20) and type of PA was not associated with sports injuries or SIBs (Spearman's rho < .15). CONCLUSION: These motor proficiency- and endurance tests were unable to predict sports injuries or SIBs in PWH, potentially due to few PWH with poor results and low numbers of sports injuries and SIBs.

Association between Sports Participation, Factor VIII Levels and Bleeding in Hemophilia A.

BACKGROUND: Little is known on how sports participation affects bleeding risk in hemophilia. This study aimed to examine associations between sports participation, factor VIII (FVIII) levels and bleeding in persons with hemophilia A. METHODS: In this observational, prospective, single-center study, persons with hemophilia A who regularly participated in sports were followed for 12 months. The associations of patient characteristics, FVIII levels, and type/frequency of sports participation with bleeding were analyzed by repeated time-to-event modelling. RESULTS: One hundred and twelve persons (median age: 24 years [interquartile range:16-34], 49% severe, 49% on prophylaxis) were included. During follow-up, 70 bleeds of which 20 sports-induced were observed. FVIII levels were inversely correlated with the bleeding hazard; a 50% reduction of the baseline bleeding hazard was observed at FVIII levels of 3.1 and a 90% reduction at 28.0 IU/dL. The bleeding hazard did not correlate with sports participation. In addition, severe hemophilia, prestudy annual bleeding rate, and presence of arthropathy showed a positive association with the bleeding hazard. CONCLUSION: This analysis showed that FVIII levels were an important determinant of the bleeding hazard, but sports participation was not. This observation most likely reflects the presence of adequate FVIII levels during sports participation in our study. Persons with severe hemophilia A exhibited a higher bleeding hazard at a similar FVIII levels than nonsevere, suggesting that the time spent at lower FVIII levels impacts overall bleeding hazard. These data may be used to counsel persons with hemophilia regarding sports participation and the necessity of adequate prophylaxis.

Promoting physical activity for people with haemophilia in the age of new treatments.

Haemophilia treatment has seen great advances in recent years with an accompanied reduced risk of physical activity (PA) related bleeds. Based on its known health benefits, people with haemophilia (PWH) are currently encouraged to regularly engage in PA. However, this may not always translate to increased levels of PA. In this narrative review we aim to provide a brief overview of what is currently understood regarding PA levels and influences for the three broad age groups of children and adolescents, adults and older adults. We also provide recommendations for members of the haemophilia team on important aspects related to promotion of PA in their clinical practice. We highlight that PA behaviour is multifactorial and that many PWH still have limited access to adequate care. Whilst some still face unique challenges to being more physically active, overall, the barriers and facilitators to activity are very similar to that of the general population.

Predicting Individual Changes in Terminal Half-Life After Switching to Extended Half-Life Concentrates in Patients With Severe Hemophilia.

Predicting individual effects of switching from standard half-life (SHL) to extended half-life (EHL) FVIII/FIX concentrates is pivotal in clinical care, but large-scale individual data are scarce. The aim of this study was to assess individual changes in terminal half-life (THL) after switching to EHL concentrates and identifying determinants of a clinically relevant THL extension in people with severe hemophilia. Data from participants with pharmacokinetic studies on both SHL and EHL were extracted from the Web-Accessible Population Pharmacokinetics Service (WAPPS) database and stratified according to hemophilia type and age groups (children/adults). A 30% increase in THL was considered clinically relevant. Predictors of a relevant increase were identified using logistic regression. Data from 688 persons with severe hemophilia (2174 infusions) were included: 89% hemophilia A; median age: 21.7 (interquartile range [IQR]: 11.5-37.7); positive inhibitor history: 11.7%. THL increased by 38% (IQR: 17%-67%) and 212% (139%-367%) for hemophilia A and B, respectively. All EHL-FIX concentrate users showed clinically relevant THL extension. However, 40% (242/612) of people with hemophilia A showed limited extension or decrease in THL after switching. Relevant FVIII-THL extension was predicted by short baseline THL and blood group non-O in both children and adults. In conclusion, clinically relevant THL extension was observed in all 75/76 participants switching to EHL-FIX, and in 60% of 612 switching to EHL-FVIII. Short THL on SHL-FVIII and blood group non-O were identified as predictors for a relevant THL increase after switching to EHL-FVIII. Individualized pharmacokinetic assessment may guide clinical decision-making when switching from SHL to EHL-FVIII.

Similar sports participation as the general population in Dutch persons with haemophilia; results from a nationwide study.

INTRODUCTION: Although sports participation is advocated in people with haemophilia (PWH), detailed data concerning sports participation in Dutch PWH is lacking. AIM: to assess sports participation in Dutch PWH (6-65 years) compared to the Dutch general population (GP). METHODS: Data from a nationwide, cross-sectional study in PWH were analysed. Sports participation (type, duration, frequency) was assessed by the Modifiable Activities Questionnaire (MAQ), limitations in activities using the (Paediatric) Haemophilia Activities List ((Ped)HAL). Sports in the two highest categories according to the National Hemophilia Foundation classification were considered high-risk sports. Groups were compared using Chi-square testing. RESULTS: A total of 524 Adult PWH (median age: 45 (IQR: 30-55); 37% severe) and 126 paediatric PWH (median age: 11 (IQR: 8-14); 52% severe) were included. Sports participation was higher in adults (70%) than the GP (58%) and similar to the GP in children (PWH: 68%, GP: 72%). High-risk sports participation decreased with age in PWH: from 65% (6-12 years) to 17% (50-65 years), which was also observed in the GP. Sports participation in children was independent of severity (non-severe: 67% vs. severe: 65%; P = 0.97), but not in adults (non-severe: 75%, severe: 62%; P < 0.01). Non-severe PWH played more high-risk sports than severe PWH: children at 65% vs. 48% (P = 0.05), adults at 25% vs. 15% (P = 0.07). DISCUSSION: These results suggest that sports participation in PWH was comparable to the GP. Sports participation was dependent of haemophilia severity in adults. Children were more involved in high-risk sports than adults. More studies on sports-related injury-risk are needed for adequate counselling.

Terminal half-life of FVIII and FIX according to age, blood group and concentrate type: Data from the WAPPS database.

BACKGROUND: Real-life data on pharmacokinetics of factor (F) VIII/IX concentrates, especially extended half-life (EHL), concentrates in large cohorts of persons with hemophilia are currently lacking. OBJECTIVES: This cross-sectional study aimed to establish reference values for terminal half-life (THL) for FVIII/IX concentrates according to concentrate type, age, blood group and inhibitor history. PATIENTS/METHODS: Data were extracted from the Web-Accessible Population Pharmacokinetics Service database. Groups were compared by nonparametric tests. THL was modelled according to patient characteristics and concentrate type. RESULTS: Infusion data (n = 8022) were collected from 4832 subjects (including 2222 children) with severe hemophilia (age: 1 month-85 years; 89% hemophilia A; 34% using EHL concentrates, 9.8% with history of inhibitors). THL of FVIII-EHL was longer than of FVIII standard half-life (SHL; median 15.1 vs. 11.1 h). FVIII-THL was dependent on age, concentrate type, blood group, and inhibitor history. THL of FIX-EHL was longer than of FIX-SHL (median 106.9 vs. 36.5 h). FIX-THL increased with age until 30 years and remained stable thereafter. FVIII-THL was shorter in subjects with blood group O. THL was decreased by 1.3 h for FVIII and 22 h for FIX in subjects with a positive inhibitor history. CONCLUSIONS: We established reference values for FVIII/IX concentrates according to patient characteristics and concentrate type in a large database of hemophilia patients. These reference values may inform clinical practice (e.g., assessment of immune tolerance success), economic implications of procurement processes and value attribution of novel treatments (e.g., mimetics, gene therapy).

Sports participation and sports injuries in Dutch boys with haemophilia.

INTRODUCTION: Sports participation in children with hemophilia is generally considered to be associated with increased injury risk, which is generally considered highest in severe hemophilia. AIM: To assess sports participation according to age and severity in children with hemophilia and its association with sports injuries. METHODS: In a retrospective single-center study, sports participation, injuries, and bleeding data from three consecutive annual clinic visits were collected for young patients with hemophilia (PWH, aged 6-18). Sports in categories 2.5 and 3 of 3 according to the National Hemophilia Foundation classification were considered high-risk. Groups were compared using chi-square testing. RESULTS: 105 PWH (median age: 13(IQR 10-14); 53% severe; bleeding rate: 1/y) were identified; three were unable to perform sports and were excluded. The majority of PWH (77%) played sports weekly, of which 80% high-risk sports. Sports participation (median 3.0x/wk), and the proportion of injured PWH was similar in severe (42%) and non-severe (33%) PWH. Sports injuries were rare (65% no injuries in 3 years, median 0/y (IQR 0-1)). Annually, PWH did not report more injuries (15%) than age-matched boys (28%). Sports injuries were not associated with frequency and type of sports. DISCUSSION: This retrospective study showed high sports participation (including high-risk sports) and low injury rates. Sports participation was similar across severities and injury rates were not higher than among the general population. Injuries were not associated with frequency or type of sports. A prospective study with objective assessment of sports participation and injuries is warranted to confirm these findings and avoid recall bias.

Sports participation and physical activity in adult Dutch and Swedish patients with severe haemophilia: A comparison between intermediate- and high-dose prophylaxis.

INTRODUCTION: Differences in treatment and outcome have been reported for persons with haemophilia (PWH) on intermediate-dose (Dutch) and high-dose (Swedish) prophylaxis, but the potential influence of sports participation has not been considered. AIM: To compare sports participation and clinical outcome between adult Dutch and Swedish PWH. METHODS: Self-reported sports participation (type and frequency per week), physical functioning (SF-36PF : 100-0), joint status (HJHS: 0-144), perceived limitations (HALsum : 100-0) and physical activity (IPAQ) were recorded. Sports were classified according to National Haemophilia Foundation classification (5 categories, highest two were classified as high-risk sports). Sports participation and clinical outcome were compared according to country and age (18-22, 23-29, 30-40 years) using non-parametric tests and Spearman correlations (rho). RESULTS: Seventy-one adult PWH (NL: 43, SWE: 28) completed sports questionnaires (mean age: 26 years). All participants engaged in sports, including 59.2% in high-risk sports (33.9% twice weekly). Dutch PWH showed a significant age-related decline in (high-risk) sports participation (7x/wk in PWH 18-22 years to 2x/wk in PWH 30-40 years, P < 0.05), joint health (HJHS: median 2-15.5, P < 0.01) and physical functioning (SF-36PF : median 100 to 77.5, P < 0.01), while Swedish did not. Sports participation was not associated with bleeding (Spearman's rho = -0.119). CONCLUSION: All participants reported sports participation, including 59.2% in high-risk sports. Dutch PWH treated with intermediate-dose prophylaxis showed an age-related decline in sports participation, joint status and physical functioning, whereas Swedish PWH on high-dose prophylaxis did not. Sports participation was not associated with bleeding.