Physical activity patterns in people with haemophilia with and without arthropathy: A cross-sectional study using wearable sensors

Physical activity patterns in people with haemophilia with and without arthropathy: A cross-sectional study using wearable sensors | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Physical activity patterns in people with haemophilia with and without arthropathy: A cross-sectional study using wearable sensors Yuya Mawarikado, Midori Shima, Naoki Matsumoto, Asuka Sakata, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8217815/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background In haemophilia, recurrent joint bleeding often results in joint destruction, which in turn leads to reduced physical activity (PA) and decreased quality of life (QOL). While maintaining high PA levels is important in the care of people with haemophilia (PwH), it remains unclear whether PwH without joint disease can maintain adequate activity levels. Aim This descriptive cross-sectional study sought to compare moderate-to-vigorous physical activity (MVPA) levels among PwH with haemophilic arthropathy (HA), PwH without HA, and non-PwH. Methods A total of 46 males wore a triaxial accelerometer (wGT3X-BT, ActiGraph) during daily activities for seven consecutive days. A bout of MVPA was defined as at least 10 consecutive minutes of moderate-intensity or higher activity. MVPA was assessed as the percentage of wear time during MVPA and the total number of MVPA bouts. Results Both PwH groups demonstrated significantly lower MVPA percentages and fewer MVPA bouts than the controls (p < 0.01). No MVPA bouts were recorded among 52.6% of PwH with HA versus 25% of PwH without HA. No significant differences were observed in sedentary or light activity between the PwH groups. Conclusions PA levels were significantly reduced in PwH, regardless of joint status, suggesting that factors beyond joint damage, such as fear of bleeding or behavioural avoidance, may play a role. These findings highlight the need for individualized, evidence-based interventions to safely promote physical activity and improve long-term health outcomes in PwH. haemophilia A haemophilia B joint diseases Figures Figure 1 Figure 2 Figure 3 Background Haemophilia is a disorder that is linked to the X chromosome and causes qualitative or quantitative abnormalities in coagulation factor VIII or IX [1]. Abnormalities in coagulation factors can cause unprovoked or provoked bleeding, with joints being the most common bleeding sites [2]. Repeated intra-articular bleeding causes structural abnormalities in the joint, leading to functional impairment and pain. This joint abnormality is called haemophilic arthropathy (HA) and is one of the major complications observed among people with haemophilia (PwH). HA is responsible for chronic pain experienced by 32–50% of PwH, thereby reducing physical activity (PA) and functionality [1, 3-5]. In recent years, significant advancements have been made in haemophilia treatment, including improvements in treatment methods such as prophylactic therapy and the development of new therapeutic agents, including nonfactor agents. Therefore, the incidence of HA has decreased significantly [6], with a particularly marked trend observed among individuals receiving new treatments from an early age. Additionally, the reduction in bleeding episodes accompanied by painful symptoms has led to a decrease in the tendency to avoid participation in sports and other physically demanding activities. It has been well established that PA offers numerous benefits for PwH. A Cochrane review demonstrated that exercise interventions for PwH contribute to pain reduction, improved joint range of motion, increased muscle strength, and enhanced walking endurance [7]. Activities with a high risk of serious injury should be avoided; however, the benefits of maintaining high levels of PA are considered to outweigh the risks of bleeding associated with exercise, and achieving PA levels comparable to those of healthy individuals is important for maintaining joint health. It has been reported that PA levels are reduced among PwH with HA; however, to our knowledge, no studies have examined PA levels among PwH without HA. While there are reports suggesting an increasing trend in sports participation among young PwH without HA, our previous study reported that even in PwH without HA, walking speed was slower and gait was more impaired than in age-matched healthy controls [8]. These results are inconsistent with the assumption that PwH without HA have PA levels equivalent to those of healthy controls. While previous studies have evaluated PA levels on the basis of the severity of haemophilia or differences between paediatric and adult populations [9-11], no reports have focused on the presence or absence of HA. In this study, we hypothesized that PwH with HA would have lower PA levels. Therefore, the aim of this study was to compare PA levels between PwH and healthy participants. These findings are expected to increase knowledge regarding PA levels among PwH and promote the development of appropriate PA strategies tailored to the modern PwH population, who experience less frequent bleeding due to advancements in treatment. Methods Study design and participants This study adopted a descriptive cross-sectional design to quantitatively compare PA levels across three groups: the PwH with HA group, the PwH without HA group, and the non-haemophilic (non-PwH) group. Male participants were recruited from Nara Medical University Hospital in Japan between 1 September, 2022 and the end of December 2024. The inclusion criterion for PwH was the ability to walk independently. The exclusion criteria were as follows: the presence of orthopaedic disorders other than HA; or any neuromuscular conditions affecting mobility. The exclusion criterion for non-PwH individuals was the presence of orthopaedic or mobility-impairing disorders. Additionally, participants who engaged in high-activity occupations, such as athletes or firefighters, were excluded from this study. The severity of HA in each joint was assessed radiologically using the Arnold–Hilgartner staging (AHS) system [12]. An orthopaedic surgeon specializing in HA diagnosed the presence or absence of HA in the knee or ankle joints. Stages 4-5 indicated HA, and stages 0-3 indicated the absence of HA. All participants were given a clear and comprehensive explanation of the study in accordance with the Declaration of Helsinki. The participants subsequently signed informed consent forms. Ethical approval for the study was obtained from both Nara Medical University (ID: 1979) and Chugai Ethics Committees (ID: E20019). Background characteristics The following data were collected from the patients’ electronic medical records: age, height, weight, body mass index (BMI), severity of haemophilia on the basis of their factor levels in plasma (severe: ≤1%; moderate: 1%−5%; and mild: >5% to ≤40%), and information on their treatment regimen (formulation name of coagulation factor concentrates and infusion interval of the concentrates). Measurement of physical activity The participants were instructed to wear a triaxial accelerometer – the wGT3X-BT (ActiGraph LLC, Pensacola, FL, USA) – on either side of their waist continuously for seven days except for during sleep and aquatic activities (Figure 1a). The data were processed using ActiLife version 6.13.4 (ActiGraph LLC). The criterion for adopting data was that valid data were obtained for at least five days. The epoch for count sampling was set to one minute. On the basis of the criteria of Sasaki et al. [13], the percentage of time spent engaging in moderate to vigorous physical activity (MVPA) was calculated (relative to total wear time). Sedentary, light, and more intense activity levels were distinguished from MVPA. The wear time was calculated in minutes. MVPA episodes lasting at least 10 consecutive minutes were defined as one bout (i.e., a single continuous session of at least moderate- intensity activity). This approach enabled the calculation of the ability to sustain at least 10 minutes of MVPA. For participants who did not complete a bout of MVPA, the number of bouts was recorded as zero. Statistical analysis The data were analysed descriptively by calculating the mean and standard deviation (SD) via statistical software. All the statistical analyses were performed using SPSS software (SPSS, Inc.; SPSS version 26.0 for Windows), and the threshold for statistical significance was set to 5%. The Shapiro‒Wilk test was performed to assess the normality of the data. One-way ANOVA and the Kruskal‒Wallis test were used to compare parameters among the three groups (PwH with HA vs. PwH without HA vs. non-PwH). Then, all pairs of groups were contrasted within each factor to search for any significant heterogeneity detected by ANOVA. If a significant difference was found via one-way ANOVA, multiple comparisons were performed via Tukey's test. If a significant difference was found via the Kruskal‒Wallis test, multiple comparisons were performed via the Steel–Dwass test. Results Background of PwH Nineteen PwH with HA, 12 PwH without HA, and 15 non-PwH were enrolled. The severity of PwH, the AHS of the ankle and knee joints, and the methods of treatment are shown in Table 1. In the PwH with HA group, 15 participants had haemophilia A, and 4 participants had haemophilia B. In the PwH without HA group, 9 participants had haemophilia A, and 3 participants had haemophilia B. There were 16 severe cases, 1 moderate case, and 2 mild cases of haemophilia in the PwH with HA group and 8 severe cases, 2 moderate cases, and 2 mild cases of haemophilia in the PwH without HA group. In the PwH with HA group, 12 participants received prophylaxis via regular clotting factor agents (factor prophylaxis), 6 participants received prophylaxis via emicizumab (emicizumab prophylaxis), and one participant received on-demand treatment. In the PwH without HA group, 9 participants received factor prophylaxis, 2 participants received emicizumab prophylaxis, and 1 participant received on-demand treatment. Four participants in the PwH with HA group experienced joint pain. No participants in the PwH without HA group experienced joint pain. All 19 participants in the PwH with HA group had AHS stage 4 or 5 arthropathy in the ankle or knee joints. None of the participants had a history of joint or intramuscular bleeding in the past year. Table 1. Severity, treatment information, pain location, and Arnold–Hilgartner stages of the ankle and knee joints in PwH and non-PwH. AHS Ankle Knee ID Age Type Severity Method of treatment Pain of lower limb Left Right Left Right PwH with HA 1 51 A Severe Emicizumab prophylaxis Right hip, Left knee 2 4 5 5 (n=19) 2 74 A Severe Emicizumab prophylaxis No pain 2 Arthrodesis 4 5 3 57 A Severe Emicizumab prophylaxis No pain 4 5 4 5 4 52 A Severe Factor prophylaxis Bilateral ankle 5 5 TKA TKA 5 60 A Severe Factor prophylaxis Bilateral ankle 3 4 5 5 6 64 B Mild On demand No pain 2 3 2 3 7 68 A Moderate Factor prophylaxis No pain 0 4 4 4 8 63 B Severe Factor prophylaxis Left knee 5 5 2 2 9 36 A inhibitor Emicizumab prophylaxis No pain 5 5 3 5 10 32 A Severe Emicizumab prophylaxis No pain 2 4 2 0 11 51 A Severe Factor prophylaxis No pain 5 4 4 4 12 27 A Severe Factor prophylaxis No pain 4 2 1 1 13 38 B Severe Factor prophylaxis No pain 5 1 0 0 14 28 A Severe Emicizumab prophylaxis No pain 5 1 4 4 15 36 A Severe Factor prophylaxis No pain 4 Arthrodesis 1 1 16 42 A Severe Factor prophylaxis No pain 5 5 2 5 17 44 A Severe Factor prophylaxis Left knee, bilateral ankle 5 Arthrodesis 1 1 18 68 B Severe Factor prophylaxis No pain 5 5 2 TKA 19 44 A Mild Factor prophylaxis No pain 5 5 5 1 PwH without HA 20 53 A Mild Factor prophylaxis No pain 0 0 1 1 (n=12) 21 50 A Moderate On demand No pain 0 0 0 0 22 27 A Severe Emicizumab prophylaxis No pain 0 0 0 0 23 19 A Moderate Factor prophylaxis No pain 0 0 0 0 24 18 A Severe Factor prophylaxis No pain 0 0 0 0 25 21 A Severe Factor prophylaxis No pain 0 0 0 0 26 21 B Severe Factor prophylaxis No pain 1 1 0 0 27 22 B Severe Factor prophylaxis No pain 1 1 0 0 28 21 A Severe Emicizumab prophylaxis No pain 0 0 0 0 29 17 B Mild Factor prophylaxis No pain 0 0 0 0 30 23 A Severe Factor prophylaxis No pain 1 1 1 1 31 21 A Severe Factor prophylaxis No pain 1 0 0 0 Non-PwH 32 28 No pain (n=15) 33 38 No pain 34 20 No pain 35 26 No pain 36 30 No pain 37 30 No pain 38 43 No pain 39 63 No pain 40 28 No pain 41 58 No pain 42 53 No pain 43 28 No pain 44 26 No pain 45 34 No pain 46 28 No pain Abbreviations: AHS, Arnold-Hilgartner staging; HA, haemophilic arthropathy; PwH, people with haemophilia; TKA, total knee arthroplasty [insert Table 1 near here] Differences in basic information and physical activity parameters among the three groups The participants’ descriptive statistics and the results of univariate analysis and multiple comparison tests are shown in Table 2. The mean ± SD age was 49.2 ± 14.4, 26.1 ± 12.2, and 35.5 ± 12.9 years for the PwH with HA, PwH without HA, and non-PwH groups, respectively. The mean ± SD heights were 165.5 ± 5.7, 175.8 ± 7.2, and 170.4 ± 8.4 cm for the PwH with HA, PwH without HA, and non-PwH groups, respectively. The mean ± SD weights were 65.0 ± 8.8, 73.3 ± 8.4, and 67.8 ± 12.0 kg for the PwH with HA, PwH without HA, and non-PwH groups, respectively. The mean ± SD BMIs were 23.7 ± 2.6, 23.8 ± 2.9, and 23.4 ± 4.5 kg/m² for the PwH with HA, PwH without HA, and non-PwH groups, respectively. The PwH without HA group was significantly younger and taller than the PwH with HA group. No significant differences in weight or BMI were observed among the three groups. Table 2. Parameters and statistical data for the three groups. PwH groups 3-arm comparison PwH with HA (n = 19) PwH without HA (n = 12) Non-PwH (n = 15) p value Statistic value Comparion among groups Age (years) 49.2 ± 14.4 26.1 ± 12.2 35.5 ± 12.9 0.001 11.454 †, ††† Height (cm) 165.5 ± 5.7 175.8 ± 7.2 170.4 ± 8.4 0.001 8.742 † Weight (kg) 65.0 ± 8.8 73.3 ± 8.4 67.8 ± 12.0 0.049 3.398 BMI (kg/m 2 ) 23.7 ± 2.6 23.8 ± 2.9 23.4 ± 4.5 0.969 0.031 Physical activity parameters Sedentary (%) 78.9 ± 12.5 78.8 ± 7.1 76.3 ± 5.8 0.549 0.612 Light activity (%) 16.7 ± 9.6 14.5 ± 3.4 12.4 ± 3.2 0.114 2.351 MVPA (%) 4.4 ± 5.2 6.7 ± 5.2 11.3 ± 3.4 0.001 11.117 ††, ††† MVPA bouts (bout) 3.3 ± 5.7 4.5 ±5.5 20.0 ± 10.2 0.001 16.148 ††, ††† Wear time (minutes) 4,846.5 ± 1,899.8 3,152.2 ± 1,619.2 4,835.6 ± 956.2 0.013 5.230 †, †† The data are expressed as the mean ± SD, with p < 0.05 indicating statistical significance. PwH: people with haemophilia, HA: haemophilic arthropathy, BMI: body mass index, MVPA: moderate to vigorous physical activity † significant difference between PwH with HA and PwH without HA, p < 0.05 †† significant difference between the PwH without HA and the non-PwH group, p < 0.05 ††† significant difference between the PwH with HA group and the non-PwH group, p < 0.05 The mean ± SD percentages of sedentary time were 78.9 ± 12.5%, 78.8 ± 7.1%, and 76.3 ± 5.8% for the PwH with HA, PwH without HA, and non-PwH groups, respectively (Figure 1a). The mean ± SD percentages of light activity were 16.7 ± 9.6%, 14.5 ± 3.4%, and 12.4 ± 3.2% for the PwH with HA, PwH without HA, and non-PwH groups, respectively (Figure 1b). The mean ± SD percentages of MVPA were 4.4 ± 5.2%, 6.7 ± 5.2%, and 11.3 ± 3.4% for the PwH with HA, PwH without HA, and non-PwH groups, respectively (Figure 1c). The mean ± SD wearing time was 4,846.5 ± 1,899.8, 3,152.2 ± 1,619.3, and 4,835.6 ± 956.2 minutes for the PwH with HA, PwH without HA, and non-PwH groups, respectively. No significant differences in the percentages of sedentary or light activity were observed across the three groups. The percentage of MVPA in the non-PwH group was significantly greater than that in both the PwH with HA and the PwH without HA groups. The wearing time of the PwH without HA group was significantly shorter than that of the PwH with HA and the non-PwH group, thus indicating lower adherence to wearing the ActiGraph. The mean ± SD numbers of MVPA bouts were 3.3 ± 5.7, 4.5 ± 5.5, and 20.0 ± 10.2 bouts for the PwH with HA, PwH without HA, and non-PwH groups, respectively (Figure 2). The number of MVPA bouts was significantly higher in the non-PwH group than in both the PwH with HA and PwH without HA groups (Figure 3). Among the PwH with HA, 10 out of 19 participants (52.6%) recorded zero MVPA bouts. In the PwH without HA group, 3 out of the 12 participants (25%) recorded zero MVPA bouts. None of the participants in the non-PwH group recorded zero MVPA bouts. Discussion This study is the first report from Japan to compare PA levels between PwH with HA and PwH without HA. The results demonstrated that PwH with HA had significantly lower percentages of MVPA and lower frequencies of MVPA bouts than non-PwHs. Furthermore, PwH without HA had significantly lower MVPA percentages and bout frequencies than non-PwHs, who were older than PwH without HA and thus were expected to have inherently lower PA levels. These results suggest a general trend towards lower PA in PwH with and without HA. These findings align with previous international reports indicating that PwH, even when clinically stable, may restrict their PA owing to perceived bleeding risks or conditioned behavioural patterns [14]. Importantly, more than half of the PwH with HA reported zero bouts of MVPA during the weeklong monitoring, highlighting a critical inactivity issue in this population. Sustained MVPA is known to be associated with improved cardiovascular and musculoskeletal health, and its absence may place PwH with HA at greater risk of comorbidities, including sarcopenia and metabolic syndrome [15, 16]. Recent advances in haemophilia treatment have reduced symptomatic joint bleeding [17], but PA behaviour among PwH who have HA has not improved accordingly. Surprisingly, PwH without HA had lower MVPA percentages than non-PwHs, despite being younger and having no structural joint damage. This finding suggests that factors unrelated to joint dysfunction, such as fear of bleeding imprinted from past bleeding experiences, low exercise self-efficacy, or avoidance of exercise due to explanations from physicians or caregivers about disease-causing bleeding, may contribute to activity limitations. In support of this, previous studies have reported that overprotective parenting and a lack of PA during childhood can have persistent effects on PA in adulthood [18, 19]. In our previous study, even in the absence of HA, PwH demonstrated gait abnormalities and reduced walking speed compared with the non-PwH group, which may also reflect reduced PA [8]. These findings underscore the importance of individualized, evidence-based PA promotion strategies for PwH, particularly those without HA. Given the documented safety and benefits of structured exercise in PwH [7], tailored interventions focusing on self-efficacy enhancement, education, and supervised physical training may be warranted. Furthermore, the use of objective tools such as accelerometry and wearable impact sensors enables clinicians to monitor activity patterns and the symmetry of limb loading in real-life settings, which can guide rehabilitation and preventative strategies aimed at preserving musculoskeletal health in modern PwH. This study has several limitations. First, the relatively small sample size, particularly in the PwH without HA group, may limit the generalizability of the findings and reduce the statistical power to detect subtle group differences. Second, the cross-sectional design precludes any causal inferences with respect to the relationship between PA levels and the presence or absence of HA. Longitudinal studies with larger, multicentre cohorts are needed to validate these findings and to explore whether reduced PA contributes to or is a consequence of the development of HA. Conclusions Our findings revealed that compared with healthy participants, haemophilia patients – regardless of the presence of arthropathy – exhibit significantly reduced PA. These findings suggest a general reduction in PA levels among PwH regardless of joint damage, which is likely influenced by psychological and behavioural factors. Given that more than half of PwH with HA reported zero bouts of sustained MVPA despite advances in prophylactic treatments, there is a critical need for individualized, evidence-based PA interventions. Tailored strategies focusing on education, self-efficacy, and objective monitoring may help bridge the gap between clinical stability and active lifestyles, thereby contributing to the long-term musculoskeletal health of PwH. Abbreviations AHS; Arnold–Hilgartner staging, BMI; Body mass index, HA; Haemophilic arthropathy, MVPA; Moderate-to-vigorous physical activity, PA; Physical activity, PwH; People with haemophilia, QOL; Quality of life, SD; Standard deviation Declarations Ethics approval and consent to participate All participants were given a clear and comprehensive explanation of the study and its purpose in accordance with the Declaration of Helsinki. The participants subsequently provided signed informed consent. Ethical approval for the study was obtained from both Nara Medical University (ID: 1979) and Chugai Ethics Committees (ID: E20019). Consent for publication No identifiable subject information is provided in the manuscript, figures, or tables. Availability of data and materials The data that support the findings of this study are available from the corresponding author upon reasonable request. Competing interests YM: Is a member of the Medicinal Biology of Thrombosis and Hemostasis , established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; has received personal fees from Bayer AG. MS: Is a member of the Medicinal Biology of Thrombosis and Hemostasis , established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; has received research funding from Chugai Pharmaceutical Co., Ltd., CSL Behring, and Takeda; has received honoraria from Bayer, Chugai Pharmaceutical Co., Ltd., CSL Behring, Fujimoto Seiyaku, Sanofi, Novo Nordisk, Pfizer, and Takeda; holds patents with Chugai Pharmaceutical Co., Ltd.; and has served on data safety monitoring boards or advisory boards for Chugai Pharmaceutical Co., Ltd., Fujimoto Seiyaku, KYORIN Pharmaceutical Co., Ltd., Novo Nordisk, and Pfizer. NS: Has received honoraria from Bayer, Chugai Pharmaceutical Co., Ltd., CSL Behring, Japan Blood Products Organization, KM Biologics, Novo Nordisk, Pfizer, Sanofi, and Takeda. NM: Is a member of the Medicinal Biology of Thrombosis and Hemostasis , established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; owns stock in Chugai Pharmaceutical Co., Ltd. AS: Is a member of the Medicinal Biology of Thrombosis and Hemostasis , established by Nara Medical University and Chugai Pharmaceutical Co., Ltd. RK: Is a member of the Medicinal Biology of Thrombosis and Hemostasis , established by Nara Medical University and Chugai Pharmaceutical Co., Ltd. KT: Is a member of the Medicinal Biology of Thrombosis and Hemostasis , established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; has received personal fees from Novo Nordisk A/S. TS: Is a member of the Medicinal Biology of Thrombosis and Hemostasis , established by Nara Medical University and Chugai Pharmaceutical Co., Ltd. SH: Is a member of the Medicinal Biology of Thrombosis and Hemostasis , established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; owns stock in Chugai Pharmaceutical Co., Ltd. NS: Reports no conflicts of interest. YI: Has received specific clinical trial funding from MediaMart Co., Ltd.; has received research funding from Chugai Pharmaceutical Co., Ltd., Johnson & Johnson K.K., KM Biologics, Olympus Terumo Biomaterials Corp., and Zimmer Biomet; has received honoraria from Asahi Kasei Pharma Corporation, Bayer Yakuhin Ltd., Chugai Pharmaceutical Co., Ltd., CSL Behring, Healios K.K., Hisamitsu Pharmaceutical Co., Johnson & Johnson K.K., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Sanofi K.K., and Takeda Pharmaceutical Co., Ltd.; and serves as a medical advisor for Chugai Pharmaceutical Co., Ltd. and KM Biologics. AK: Has received grants or research support from Chugai Pharmaceutical Co., Ltd. KN: Is a member of the Medicinal Biology of Thrombosis and Hemostasis , established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; has received grants, personal fees, and nonfinancial support from Chugai Pharmaceutical Co., Ltd.; personal fees from F. Hoffmann-La Roche Ltd.; has received grants, personal fees, and nonfinancial support from Sysmex Co.; has received grants and personal fees from Takeda Pharmaceutical Co.; has received grants and personal fees from Sanofi S.A.; has received personal fees from CSL Behring Co.; has received grants and personal fees from KM Biologics Co.; grants and personal fees from Novo Nordisk A/S; has received grants and personal fees from Bayer AG; has received grants and personal fees from Bioverativ Inc.; has received grants and personal fees from Shire Plc; and is a coinventor of a patent related to an anti-FIXa/FX bispecific antibody. Funding Chugai Pharmaceutical Co., Ltd. Authors’ contributions Conceptualization: YM, MS, NM, AS, RK, KT, TS, SH, and KN. Data curation: YM, MS, NM, AS, NS, YI, AK, and KN. Formal analysis: YM, MS, NM, AS, RK, KT, TS, SH, and KN. Investigation: YM, MS AS, KT, NS, YI, AK, and KN. Methodology: YM, MS, NM, AS, RK, KT, TS, SH, and KN. Project administration: YM, MS, NM, AS, RK, KT, TS, SH, and KN. Resources: YM, MS, AS, KT, NS, AK, and KN. Supervision: YM, MS, and KN. Visualization: YM, MS, NM, AS, RK, KT, TS, SH, and KN. Writing -original draft: All the authors. Writing -review and editing: All the authors. Acknowledgements We thank the participants who were involved in the measurements. We thank American Journal Experts (AJE) for their help with English language editing. References Srivastava A, Santagostino E, Dougall A, Kitchen S, Sutherland M, Pipe SW, et al. WFH guidelines for the management of hemophilia, 3rd edition. Haemophilia. 2020;26:1-158. Knobe K, Berntorp E. 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Health Psychol Open. 2021;8:20551029211039920. Goto M, Takedani H, Yokota K, Haga N. Strategies to encourage physical activity in patients with hemophilia to improve quality of life. J Blood Med. 2016;7:85-98. Additional Declarations Competing interest reported. YM: Is a member of the Medicinal Biology of Thrombosis and Hemostasis, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; has received personal fees from Bayer AG. MS: Is a member of the Medicinal Biology of Thrombosis and Hemostasis, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; has received research funding from Chugai Pharmaceutical Co., Ltd., CSL Behring, and Takeda; has received honoraria from Bayer, Chugai Pharmaceutical Co., Ltd., CSL Behring, Fujimoto Seiyaku, Sanofi, Novo Nordisk, Pfizer, and Takeda; holds patents with Chugai Pharmaceutical Co., Ltd.; and has served on data safety monitoring boards or advisory boards for Chugai Pharmaceutical Co., Ltd., Fujimoto Seiyaku, KYORIN Pharmaceutical Co., Ltd., Novo Nordisk, and Pfizer. NS: Has received honoraria from Bayer, Chugai Pharmaceutical Co., Ltd., CSL Behring, Japan Blood Products Organization, KM Biologics, Novo Nordisk, Pfizer, Sanofi, and Takeda. NM: Is a member of the Medicinal Biology of Thrombosis and Hemostasis, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; owns stock in Chugai Pharmaceutical Co., Ltd. AS: Is a member of the Medicinal Biology of Thrombosis and Hemostasis, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd. RK: Is a member of the Medicinal Biology of Thrombosis and Hemostasis, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd. KT: Is a member of the Medicinal Biology of Thrombosis and Hemostasis, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; has received personal fees from Novo Nordisk A/S. TS: Is a member of the Medicinal Biology of Thrombosis and Hemostasis, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd. SH: Is a member of the Medicinal Biology of Thrombosis and Hemostasis, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; owns stock in Chugai Pharmaceutical Co., Ltd. NS: Reports no conflicts of interest. YI: Has received specific clinical trial funding from MediaMart Co., Ltd.; has received research funding from Chugai Pharmaceutical Co., Ltd., Johnson & Johnson K.K., KM Biologics, Olympus Terumo Biomaterials Corp., and Zimmer Biomet; has received honoraria from Asahi Kasei Pharma Corporation, Bayer Yakuhin Ltd., Chugai Pharmaceutical Co., Ltd., CSL Behring, Healios K.K., Hisamitsu Pharmaceutical Co., Johnson & Johnson K.K., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Sanofi K.K., and Takeda Pharmaceutical Co., Ltd.; and serves as a medical advisor for Chugai Pharmaceutical Co., Ltd. and KM Biologics. AK: Has received grants or research support from Chugai Pharmaceutical Co., Ltd. KN: Is a member of the Medicinal Biology of Thrombosis and Hemostasis, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; has received grants, personal fees, and nonfinancial support from Chugai Pharmaceutical Co., Ltd.; personal fees from F. Hoffmann-La Roche Ltd.; has received grants, personal fees, and nonfinancial support from Sysmex Co.; has received grants and personal fees from Takeda Pharmaceutical Co.; has received grants and personal fees from Sanofi S.A.; has received personal fees from CSL Behring Co.; has received grants and personal fees from KM Biologics Co.; grants and personal fees from Novo Nordisk A/S; has received grants and personal fees from Bayer AG; has received grants and personal fees from Bioverativ Inc.; has received grants and personal fees from Shire Plc; and is a coinventor of a patent related to an anti-FIXa/FX bispecific antibody. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 19 Dec, 2025 Reviews received at journal 10 Dec, 2025 Reviewers agreed at journal 08 Dec, 2025 Reviewers agreed at journal 03 Dec, 2025 Reviews received at journal 01 Dec, 2025 Reviewers agreed at journal 01 Dec, 2025 Reviewers invited by journal 01 Dec, 2025 Editor assigned by journal 27 Nov, 2025 Submission checks completed at journal 27 Nov, 2025 First submitted to journal 26 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8217815","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":555115228,"identity":"cefeb913-be98-46cb-ae51-d790a3c81884","order_by":0,"name":"Yuya Mawarikado","email":"data:image/png;base64,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","orcid":"","institution":"Nara Medical University","correspondingAuthor":true,"prefix":"","firstName":"Yuya","middleName":"","lastName":"Mawarikado","suffix":""},{"id":555115229,"identity":"bc39a88b-8359-4428-8a92-0c206c04ab76","order_by":1,"name":"Midori Shima","email":"","orcid":"","institution":"Nara Medical 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(Japan)","correspondingAuthor":false,"prefix":"","firstName":"Ryohei","middleName":"","lastName":"Kawasaki","suffix":""},{"id":555115233,"identity":"c0ab5ddc-ce9b-40bb-be6b-ea7bcc2a7462","order_by":5,"name":"Kohei Tatsumi","email":"","orcid":"","institution":"Nara Medical University","correspondingAuthor":false,"prefix":"","firstName":"Kohei","middleName":"","lastName":"Tatsumi","suffix":""},{"id":555115234,"identity":"dcc7e29f-9aff-4d6a-bb10-d78ea4486b92","order_by":6,"name":"Tetsuhiro Soeda","email":"","orcid":"","institution":"Chugai Pharma (Japan)","correspondingAuthor":false,"prefix":"","firstName":"Tetsuhiro","middleName":"","lastName":"Soeda","suffix":""},{"id":555115235,"identity":"f8befdbe-9589-44b6-9eee-f52bf731576a","order_by":7,"name":"Suguru Harada","email":"","orcid":"","institution":"Chugai Pharma 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11:12:50","extension":"html","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":126873,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8217815/v1/261ee32cb31822aa8f278e05.html"},{"id":97521025,"identity":"5fad4245-91a2-4e76-aeb1-d73fb6a4c540","added_by":"auto","created_at":"2025-12-05 11:12:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":288933,"visible":true,"origin":"","legend":"\u003cp\u003eActivity levels among the three groups.\u003c/p\u003e\n\u003cp\u003e(a) Percentage of sedentary time;\u003c/p\u003e\n\u003cp\u003e(b) Percentage of light physical activity;\u003c/p\u003e\n\u003cp\u003e(c) Percentage of moderate to vigorous physical activity (MVPA).\u003c/p\u003e\n\u003cp\u003eThe data are shown as box-and-whisker plots representing the interquartile range (IQR), median (centre line), and minimum/maximum values, excluding outliers. MVPA was significantly lower in both the PwH with HA and the PwH without HA groups than in the non-PwH controls. No significant differences were found in sedentary or light activity among the groups. * p\u0026lt;0.05\u003c/p\u003e\n\u003cp\u003ePwH: people with haemophilia; HA: haemophilic arthropathy; n.s.: not significant.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8217815/v1/dd37f86e4d08800e288c21e5.png"},{"id":97671340,"identity":"89e0967b-d96a-49cb-896b-1bfba7f66526","added_by":"auto","created_at":"2025-12-08 09:32:30","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":19929,"visible":true,"origin":"","legend":"\u003cp\u003eNumber of MVPA bouts (≥10 minutes) among the three groups.\u003c/p\u003e\n\u003cp\u003eBox-and-whisker plots showing the distribution of MVPA bouts (continuous sessions of MVPA lasting ≥10 minutes) across the PwH with HA, PwH without HA, and non-PwH groups. Compared with the PwH group, the non-PwH group recorded significantly more MVPA bouts. * p\u0026lt;0.05\u003c/p\u003e\n\u003cp\u003eMVPA: moderate to vigorous physical activity; PwH: people with haemophilia; HA: haemophilic arthropathy.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8217815/v1/d0d4291ae5d2dc3887f8de4b.png"},{"id":97521024,"identity":"d52ed836-91cd-49e1-8e09-607db531ed56","added_by":"auto","created_at":"2025-12-05 11:12:50","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":49117,"visible":true,"origin":"","legend":"\u003cp\u003eIndividual MVPA bout frequency for each individual.\u003c/p\u003e\n\u003cp\u003eBar graph illustrating the number of MVPA bouts achieved by each individual across the three groups. Over half of the PwH with HA (10 of 19) and one quarter of the PwH without HA (3 of 12) recorded zero MVPA bouts. All non-PwH individuals achieved at least one MVPA bout. This figure highlights the large interindividual variability and the prevalence of physical inactivity among PwH, especially those with HA.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8217815/v1/5d35831d07eee2eb9473ca44.png"},{"id":97677831,"identity":"81f02287-bba4-4caf-87bb-21ef85e6c0a0","added_by":"auto","created_at":"2025-12-08 09:54:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1293110,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8217815/v1/a1691b74-9d81-4c2d-a75c-d05dd172da2a.pdf"}],"financialInterests":"Competing interest reported. YM: Is a member of the Medicinal Biology of Thrombosis and Hemostasis, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; has received personal fees from Bayer AG.\nMS: Is a member of the Medicinal Biology of Thrombosis and Hemostasis, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; has received research funding from Chugai Pharmaceutical Co., Ltd., CSL Behring, and Takeda; has received honoraria from Bayer, Chugai Pharmaceutical Co., Ltd., CSL Behring, Fujimoto Seiyaku, Sanofi, Novo Nordisk, Pfizer, and Takeda; holds patents with Chugai Pharmaceutical Co., Ltd.; and has served on data safety monitoring boards or advisory boards for Chugai Pharmaceutical Co., Ltd., Fujimoto Seiyaku, KYORIN Pharmaceutical Co., Ltd., Novo Nordisk, and Pfizer.\nNS: Has received honoraria from Bayer, Chugai Pharmaceutical Co., Ltd., CSL Behring, Japan Blood Products Organization, KM Biologics, Novo Nordisk, Pfizer, Sanofi, and Takeda.\nNM: Is a member of the Medicinal Biology of Thrombosis and Hemostasis, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; owns stock in Chugai Pharmaceutical Co., Ltd.\nAS: Is a member of the Medicinal Biology of Thrombosis and Hemostasis, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.\nRK: Is a member of the Medicinal Biology of Thrombosis and Hemostasis, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.\nKT: Is a member of the Medicinal Biology of Thrombosis and Hemostasis, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; has received personal fees from Novo Nordisk A/S.\nTS: Is a member of the Medicinal Biology of Thrombosis and Hemostasis, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.\nSH: Is a member of the Medicinal Biology of Thrombosis and Hemostasis, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; owns stock in Chugai Pharmaceutical Co., Ltd.\nNS: Reports no conflicts of interest.\nYI: Has received specific clinical trial funding from MediaMart Co., Ltd.; has received research funding from Chugai Pharmaceutical Co., Ltd., Johnson \u0026 Johnson K.K., KM Biologics, Olympus Terumo Biomaterials Corp., and Zimmer Biomet; has received honoraria from Asahi Kasei Pharma Corporation, Bayer Yakuhin Ltd., Chugai Pharmaceutical Co., Ltd., CSL Behring, Healios K.K., Hisamitsu Pharmaceutical Co., Johnson \u0026 Johnson K.K., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Sanofi K.K., and Takeda Pharmaceutical Co., Ltd.; and serves as a medical advisor for Chugai Pharmaceutical Co., Ltd. and KM Biologics.\nAK: Has received grants or research support from Chugai Pharmaceutical Co., Ltd.\nKN: Is a member of the Medicinal Biology of Thrombosis and Hemostasis, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; has received grants, personal fees, and nonfinancial support from Chugai Pharmaceutical Co., Ltd.; personal fees from F. Hoffmann-La Roche Ltd.; has received grants, personal fees, and nonfinancial support from Sysmex Co.; has received grants and personal fees from Takeda Pharmaceutical Co.; has received grants and personal fees from Sanofi S.A.; has received personal fees from CSL Behring Co.; has received grants and personal fees from KM Biologics Co.; grants and personal fees from Novo Nordisk A/S; has received grants and personal fees from Bayer AG; has received grants and personal fees from Bioverativ Inc.; has received grants and personal fees from Shire Plc; and is a coinventor of a patent related to an anti-FIXa/FX bispecific antibody.","formattedTitle":"Physical activity patterns in people with haemophilia with and without arthropathy: A cross-sectional study using wearable sensors","fulltext":[{"header":"Background","content":"\u003cp\u003eHaemophilia is a disorder that is linked to the X chromosome and causes qualitative or quantitative abnormalities in coagulation factor VIII or IX [1].\u003csup\u003e\u0026nbsp;\u003c/sup\u003eAbnormalities in coagulation factors can cause unprovoked or provoked bleeding, with joints being the most common bleeding sites [2]. Repeated intra-articular bleeding causes structural abnormalities in the joint, leading to functional impairment and pain. This joint abnormality is called haemophilic arthropathy (HA) and is one of the major complications observed among people with haemophilia (PwH). HA is responsible for chronic pain experienced by 32\u0026ndash;50% of PwH, thereby reducing physical activity (PA) and functionality [1, 3-5].\u003c/p\u003e\n\u003cp\u003eIn recent years, significant advancements have been made in haemophilia treatment, including improvements in treatment methods such as prophylactic therapy and the development of new therapeutic agents, including nonfactor agents. Therefore, the incidence of HA has decreased significantly [6], with a particularly marked trend observed among individuals receiving new treatments from an early age. Additionally, the reduction in bleeding episodes accompanied by painful symptoms has led to a decrease in the tendency to avoid participation in sports and other physically demanding activities. It has been well established that PA offers numerous benefits for PwH. A Cochrane review demonstrated that exercise interventions for PwH contribute to pain reduction, improved joint range of motion, increased muscle strength, and enhanced walking endurance [7]. Activities with a high risk of serious injury should be avoided; however, the benefits of maintaining high levels of PA are considered to outweigh the risks of bleeding associated with exercise, and achieving PA levels comparable to those of healthy individuals is important for maintaining joint health.\u003c/p\u003e\n\u003cp\u003eIt has been reported that PA levels are reduced among PwH with HA; however, to our knowledge, no studies have examined PA levels among PwH without HA. While there are reports suggesting an increasing trend in sports participation among young PwH without HA, our previous study reported that even in PwH without HA, walking speed was slower and gait was more impaired than in age-matched healthy controls [8]. These results are inconsistent with the assumption that PwH without HA have PA levels equivalent to those of healthy controls. While previous studies have evaluated PA levels on the basis of the severity of haemophilia or differences between paediatric and adult populations [9-11],\u003csup\u003e\u0026nbsp;\u003c/sup\u003eno reports have focused on the presence or absence of HA. In this study, we hypothesized that PwH with HA would have lower PA levels. Therefore, the aim of this study was to compare PA levels between PwH and healthy participants. These findings are expected to increase knowledge regarding PA levels among PwH and promote the development of appropriate PA strategies tailored to the modern PwH population, who experience less frequent bleeding due to advancements in treatment.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy design and participants\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study adopted a descriptive cross-sectional design to quantitatively compare PA levels across three groups: the PwH with HA group, the PwH without HA group, and the non-haemophilic (non-PwH) group. Male participants were recruited from Nara Medical University Hospital in Japan between 1 September, 2022 and the end of December 2024.\u003c/p\u003e\n\u003cp\u003eThe inclusion criterion for PwH was the ability to walk independently. The exclusion criteria were as follows: the presence of orthopaedic disorders other than HA; or any neuromuscular conditions affecting mobility. The exclusion criterion for non-PwH individuals was the presence of orthopaedic or mobility-impairing disorders. Additionally, participants who engaged in high-activity occupations, such as athletes or firefighters, were excluded from this study.\u003c/p\u003e\n\u003cp\u003eThe severity of HA in each joint was assessed radiologically using the Arnold\u0026ndash;Hilgartner staging (AHS) system [12]. An orthopaedic surgeon specializing in HA diagnosed the presence or absence of HA in the knee or ankle joints. Stages 4-5 indicated HA, and stages 0-3 indicated the absence of HA.\u003c/p\u003e\n\u003cp\u003eAll participants were given a clear and comprehensive explanation of the study in accordance with the Declaration of Helsinki. The participants subsequently signed informed consent forms. Ethical approval for the study was obtained from both Nara Medical University (ID: 1979) and Chugai Ethics Committees (ID: E20019).\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eBackground characteristics\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe following data were collected from the patients\u0026rsquo; electronic medical records: age, height, weight, body mass index (BMI), severity of haemophilia on the basis of their factor levels in plasma (severe: \u0026le;1%; moderate: 1%\u0026minus;5%; and mild: \u0026gt;5% to \u0026le;40%), and information on their treatment regimen (formulation name of coagulation factor concentrates and infusion interval of the concentrates).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eMeasurement of physical activity\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe participants were instructed to wear a triaxial accelerometer \u0026ndash; the wGT3X-BT (ActiGraph LLC, Pensacola, FL, USA) \u0026ndash; on either side of their waist continuously for seven days except for during sleep and aquatic activities (Figure 1a). The data were processed using ActiLife version 6.13.4 (ActiGraph LLC). The criterion for adopting data was that valid data were obtained for at least five days. The epoch for count sampling was set to one minute.\u003c/p\u003e\n\u003cp\u003eOn the basis of the criteria of Sasaki et al. [13], the percentage of time spent engaging in moderate to vigorous physical activity (MVPA) was calculated (relative to total wear time). Sedentary, light, and more intense activity levels were distinguished from MVPA. The wear time was calculated in minutes.\u003c/p\u003e\n\u003cp\u003eMVPA episodes lasting at least 10 consecutive minutes were defined as one bout (i.e., a single continuous session of at least moderate- intensity activity). This approach enabled the calculation of the ability to sustain at least 10 minutes of MVPA. For participants who did not complete a bout of MVPA, the number of bouts was recorded as zero.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data were analysed descriptively by calculating the mean and standard deviation (SD) via statistical software. All the statistical analyses were performed using SPSS software (SPSS, Inc.; SPSS version 26.0 for Windows), and the threshold for statistical significance was set to 5%. The Shapiro‒Wilk test was performed to assess the normality of the data.\u003c/p\u003e\n\u003cp\u003eOne-way ANOVA and the Kruskal‒Wallis test were used to compare parameters among the three groups (PwH with HA vs. PwH without HA vs. non-PwH). Then, all pairs of groups were contrasted within each factor to search for any significant heterogeneity detected by ANOVA. If a significant difference was found via one-way ANOVA, multiple comparisons were performed via Tukey\u0026apos;s test. If a significant difference was found via the Kruskal‒Wallis test, multiple comparisons were performed via the Steel\u0026ndash;Dwass test.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eBackground of PwH\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNineteen PwH with HA, 12 PwH without HA, and 15 non-PwH were enrolled. The severity of PwH, the AHS of the ankle and knee joints, and the methods of treatment are shown in Table 1. In the PwH with HA group, 15 participants had haemophilia A, and 4 participants had haemophilia B. In the PwH without HA group, 9 participants had haemophilia A, and 3 participants had haemophilia B. There were 16 severe cases, 1 moderate case, and 2 mild cases of haemophilia in the PwH with HA group and 8 severe cases, 2 moderate cases, and 2 mild cases of haemophilia in the PwH without HA group. In the PwH with HA group, 12 participants received prophylaxis via regular clotting factor agents (factor prophylaxis), 6 participants received prophylaxis via emicizumab (emicizumab prophylaxis), and one participant received on-demand treatment. In the PwH without HA group, 9 participants received factor prophylaxis, 2 participants received emicizumab prophylaxis, and 1 participant received on-demand treatment. Four participants in the PwH with HA group experienced joint pain. No participants in the PwH without HA group experienced joint pain. All 19 participants in the PwH with HA group had AHS stage 4 or 5 arthropathy in the ankle or knee joints. None of the participants had a history of joint or intramuscular bleeding in the past year.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eSeverity, treatment information, pain location, and Arnold\u0026ndash;Hilgartner stages of the ankle and knee joints in PwH and non-PwH.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"865\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" valign=\"bottom\" style=\"width: 249px;\"\u003e\n \u003cp\u003eAHS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 145px;\"\u003e\n \u003cp\u003eAnkle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 104px;\"\u003e\n \u003cp\u003eKnee\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003eID\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eType\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSeverity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eMethod of treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003ePain of lower limb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003eLeft\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eLeft\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003ePwH with HA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eEmicizumab prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eRight hip, Left knee\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e(n=19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eEmicizumab prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003eArthrodesis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eEmicizumab prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eBilateral ankle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eTKA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003eTKA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eBilateral ankle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eOn demand\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eLeft knee\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003einhibitor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eEmicizumab prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eEmicizumab prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eEmicizumab prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003eArthrodesis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eLeft knee, bilateral ankle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003eArthrodesis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003eTKA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003ePwH without HA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e(n=12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eOn demand\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eEmicizumab prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eEmicizumab prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eMild\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003eSevere\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003eFactor prophylaxis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003eNon-PwH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e(n=15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 38px;\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 40px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 76px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 161px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 132px;\"\u003e\n \u003cp\u003eNo pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 88px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 57px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: AHS, Arnold-Hilgartner staging; HA, haemophilic arthropathy; PwH, people with haemophilia; TKA, total knee arthroplasty\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e[insert Table 1 near here]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eDifferences in basic information and physical activity parameters among the three groups\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe participants\u0026rsquo; descriptive statistics and the results of univariate analysis and multiple comparison tests are shown in Table 2. The mean \u0026plusmn; SD age was 49.2 \u0026plusmn; 14.4, 26.1 \u0026plusmn; 12.2, and 35.5 \u0026plusmn; 12.9 years for the PwH with HA, PwH without HA, and non-PwH groups, respectively. The mean \u0026plusmn; SD heights were 165.5 \u0026plusmn; 5.7, 175.8 \u0026plusmn; 7.2, and 170.4 \u0026plusmn; 8.4 cm for the PwH with HA, PwH without HA, and non-PwH groups, respectively. The mean \u0026plusmn; SD weights were 65.0 \u0026plusmn; 8.8, 73.3 \u0026plusmn; 8.4, and 67.8 \u0026plusmn; 12.0 kg for the PwH with HA, PwH without HA, and non-PwH groups, respectively. The mean \u0026plusmn; SD BMIs were 23.7 \u0026plusmn; 2.6, 23.8 \u0026plusmn; 2.9, and 23.4 \u0026plusmn; 4.5 kg/m\u0026sup2; for the PwH with HA, PwH without HA, and non-PwH groups, respectively. The PwH without HA group was significantly younger and taller than the PwH with HA group. No significant differences in weight or BMI were observed among the three groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Parameters and statistical data for the three groups.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"895\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 246px;\"\u003e\n \u003cp\u003ePwH groups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 321px;\"\u003e\n \u003cp\u003e3-arm comparison\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003ePwH with HA\u003cbr\u003e\u0026nbsp;(n = 19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003ePwH without HA\u003cbr\u003e\u0026nbsp;(n = 12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003eNon-PwH\u003cbr\u003e\u0026nbsp;(n = 15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003eStatistic value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003eComparion among groups\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e49.2 \u0026plusmn; 14.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e26.1 \u0026plusmn; 12.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e35.5 \u0026plusmn; 12.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e11.454\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e\u0026dagger;, \u0026dagger;\u0026dagger;\u0026dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003eHeight (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e165.5 \u0026plusmn; 5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e175.8 \u0026plusmn; 7.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e170.4 \u0026plusmn; 8.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e8.742\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e\u0026dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003eWeight (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e65.0 \u0026plusmn; 8.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e73.3 \u0026plusmn; 8.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e67.8 \u0026plusmn; 12.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.049\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e3.398\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e23.7 \u0026plusmn; 2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e23.8 \u0026plusmn; 2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e23.4 \u0026plusmn; 4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.969\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e0.031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePhysical activity parameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003eSedentary (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e78.9 \u0026plusmn; 12.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e78.8 \u0026plusmn; 7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e76.3 \u0026plusmn; 5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.549\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e0.612\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003eLight activity (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e16.7 \u0026plusmn; 9.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e14.5 \u0026plusmn; 3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e12.4 \u0026plusmn; 3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.114\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e2.351\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003eMVPA (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e4.4 \u0026plusmn; 5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e6.7 \u0026plusmn; 5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e11.3 \u0026plusmn; 3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e11.117\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e\u0026dagger;\u0026dagger;, \u0026dagger;\u0026dagger;\u0026dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003eMVPA bouts (bout)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e3.3 \u0026plusmn; 5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e4.5 \u0026plusmn;5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e20.0 \u0026plusmn; 10.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e16.148\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e\u0026dagger;\u0026dagger;, \u0026dagger;\u0026dagger;\u0026dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003eWear time (minutes)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e4,846.5 \u0026plusmn; 1,899.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 123px;\"\u003e\n \u003cp\u003e3,152.2 \u0026plusmn; 1,619.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 124px;\"\u003e\n \u003cp\u003e4,835.6 \u0026plusmn; 956.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 128px;\"\u003e\n \u003cp\u003e5.230\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e\u0026dagger;, \u0026nbsp;\u0026dagger;\u0026dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe data are expressed as the mean \u0026plusmn; SD, with p \u0026lt; 0.05 indicating statistical significance.\u003c/p\u003e\n\u003cp\u003ePwH: people with haemophilia, HA: haemophilic arthropathy, BMI: body mass index, MVPA: moderate to vigorous physical activity\u003c/p\u003e\n\u003cp\u003e\u0026dagger; significant difference between PwH with HA and PwH without HA, p \u0026lt; 0.05\u003c/p\u003e\n\u003cp\u003e\u0026dagger;\u0026dagger; significant difference between the PwH without HA and the non-PwH group, p \u0026lt; 0.05\u003c/p\u003e\n\u003cp\u003e\u0026dagger;\u0026dagger;\u0026dagger; significant difference between the PwH with HA group and the non-PwH group, p \u0026lt; 0.05\u003c/p\u003e\n\u003cp\u003eThe mean \u0026plusmn; SD percentages of sedentary time were 78.9 \u0026plusmn; 12.5%, 78.8 \u0026plusmn; 7.1%, and 76.3 \u0026plusmn; 5.8% for the PwH with HA, PwH without HA, and non-PwH groups, respectively (Figure 1a). The mean \u0026plusmn; SD percentages of light activity were 16.7 \u0026plusmn; 9.6%, 14.5 \u0026plusmn; 3.4%, and 12.4 \u0026plusmn; 3.2% for the PwH with HA, PwH without HA, and non-PwH groups, respectively (Figure 1b). The mean \u0026plusmn; SD percentages of MVPA were 4.4 \u0026plusmn; 5.2%, 6.7 \u0026plusmn; 5.2%, and 11.3 \u0026plusmn; 3.4% for the PwH with HA, PwH without HA, and non-PwH groups, respectively (Figure 1c). The mean \u0026plusmn; SD wearing time was 4,846.5 \u0026plusmn; 1,899.8, 3,152.2 \u0026plusmn; 1,619.3, and 4,835.6 \u0026plusmn; 956.2 minutes for the PwH with HA, PwH without HA, and non-PwH groups, respectively. No significant differences in the percentages of sedentary or light activity were observed across the three groups. The percentage of MVPA in the non-PwH group was significantly greater than that in both the PwH with HA and the PwH without HA groups. The wearing time of the PwH without HA group was significantly shorter than that of the PwH with HA and the non-PwH group, thus indicating lower adherence to wearing the ActiGraph.\u003c/p\u003e\n\u003cp\u003eThe mean \u0026plusmn; SD numbers of MVPA bouts were 3.3 \u0026plusmn; 5.7, 4.5 \u0026plusmn; 5.5, and 20.0 \u0026plusmn; 10.2 bouts for the PwH with HA, PwH without HA, and non-PwH groups, respectively (Figure 2). The number of MVPA bouts was significantly higher in the non-PwH group than in both the PwH with HA and PwH without HA groups (Figure 3). Among the PwH with HA, 10 out of 19 participants (52.6%) recorded zero MVPA bouts. In the PwH without HA group, 3 out of the 12 participants (25%) recorded zero MVPA bouts. None of the participants in the non-PwH group recorded zero MVPA bouts.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study is the first report from Japan to compare PA levels between PwH with HA and PwH without HA. The results demonstrated that PwH with HA had significantly lower percentages of MVPA and lower frequencies of MVPA bouts than non-PwHs. Furthermore, PwH without HA had significantly lower MVPA percentages and bout frequencies than non-PwHs, who were older than PwH without HA and thus were expected to have inherently lower PA levels. These results suggest a general trend towards lower PA in PwH with and without HA. These findings align with previous international reports indicating that PwH, even when clinically stable, may restrict their PA owing to perceived bleeding risks or conditioned behavioural patterns [14].\u003c/p\u003e\n\u003cp\u003eImportantly, more than half of the PwH with HA reported zero bouts of MVPA during the weeklong monitoring, highlighting a critical inactivity issue in this population. Sustained MVPA is known to be associated with improved cardiovascular and musculoskeletal health, and its absence may place PwH with HA at greater risk of comorbidities, including sarcopenia and metabolic syndrome [15, 16]. Recent advances in haemophilia treatment have reduced symptomatic joint bleeding [17], but PA behaviour among PwH who have HA has not improved accordingly.\u003c/p\u003e\n\u003cp\u003eSurprisingly, PwH without HA had lower MVPA percentages than non-PwHs, despite being younger and having no structural joint damage. This finding suggests that factors unrelated to joint dysfunction, such as fear of bleeding imprinted from past bleeding experiences, low exercise self-efficacy, or avoidance of exercise due to explanations from physicians or caregivers about disease-causing bleeding, may contribute to activity limitations. In support of this, previous studies have reported that overprotective parenting and a lack of PA during childhood can have persistent effects on PA in adulthood [18, 19]. In our previous study, even in the absence of HA, PwH demonstrated gait abnormalities and reduced walking speed compared with the non-PwH group, which may also reflect reduced PA [8].\u003c/p\u003e\n\u003cp\u003eThese findings underscore the importance of individualized, evidence-based PA promotion strategies for PwH, particularly those without HA. Given the documented safety and benefits of structured exercise in PwH [7], tailored interventions focusing on self-efficacy enhancement, education, and supervised physical training may be warranted. Furthermore, the use of objective tools such as accelerometry and wearable impact sensors enables clinicians to monitor activity patterns and the symmetry of limb loading in real-life settings, which can guide rehabilitation and preventative strategies aimed at preserving musculoskeletal health in modern PwH.\u003c/p\u003e\n\u003cp\u003eThis study has several limitations. First, the relatively small sample size, particularly in the PwH without HA group, may limit the generalizability of the findings and reduce the statistical power to detect subtle group differences. Second, the cross-sectional design precludes any causal inferences with respect to the relationship between PA levels and the presence or absence of HA. Longitudinal studies with larger, multicentre cohorts are needed to validate these findings and to explore whether reduced PA contributes to or is a consequence of the development of HA.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eOur findings revealed that compared with healthy participants, haemophilia patients \u0026ndash; regardless of the presence of arthropathy \u0026ndash; exhibit significantly reduced PA. These findings suggest a general reduction in PA levels among PwH regardless of joint damage, which is likely influenced by psychological and behavioural factors. Given that more than half of PwH with HA reported zero bouts of sustained MVPA despite advances in prophylactic treatments, there is a critical need for individualized, evidence-based PA interventions. Tailored strategies focusing on education, self-efficacy, and objective monitoring may help bridge the gap between clinical stability and active lifestyles, thereby contributing to the long-term musculoskeletal health of PwH.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAHS; Arnold\u0026ndash;Hilgartner staging, BMI; Body mass index, HA; Haemophilic arthropathy, MVPA; Moderate-to-vigorous physical activity, PA; Physical activity, PwH; People with haemophilia, QOL; Quality of life, SD; Standard deviation\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants were given a clear and comprehensive explanation of the study and its purpose in accordance with the Declaration of Helsinki. The participants subsequently provided signed informed consent. Ethical approval for the study was obtained from both Nara Medical University (ID: 1979) and Chugai Ethics Committees (ID: E20019).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo identifiable subject information is provided in the manuscript, figures, or tables.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYM:\u003c/strong\u003e Is a member of the \u003cem\u003eMedicinal Biology of Thrombosis and Hemostasis\u003c/em\u003e, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; has received personal fees from Bayer AG.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMS:\u003c/strong\u003e Is a member of the \u003cem\u003eMedicinal Biology of Thrombosis and Hemostasis\u003c/em\u003e, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; has received research funding from Chugai Pharmaceutical Co., Ltd., CSL Behring, and Takeda; has received honoraria from Bayer, Chugai Pharmaceutical Co., Ltd., CSL Behring, Fujimoto Seiyaku, Sanofi, Novo Nordisk, Pfizer, and Takeda; holds patents with Chugai Pharmaceutical Co., Ltd.; and has served on data safety monitoring boards or advisory boards for Chugai Pharmaceutical Co., Ltd., Fujimoto Seiyaku, KYORIN Pharmaceutical Co., Ltd., Novo Nordisk, and Pfizer.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNS:\u003c/strong\u003e Has received honoraria from Bayer, Chugai Pharmaceutical Co., Ltd., CSL Behring, Japan Blood Products Organization, KM Biologics, Novo Nordisk, Pfizer, Sanofi, and Takeda.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNM:\u003c/strong\u003e Is a member of the \u003cem\u003eMedicinal Biology of Thrombosis and Hemostasis\u003c/em\u003e, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; owns stock in Chugai Pharmaceutical Co., Ltd.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAS:\u003c/strong\u003e Is a member of the \u003cem\u003eMedicinal Biology of Thrombosis and Hemostasis\u003c/em\u003e, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRK:\u003c/strong\u003e Is a member of the \u003cem\u003eMedicinal Biology of Thrombosis and Hemostasis\u003c/em\u003e, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eKT:\u003c/strong\u003e Is a member of the \u003cem\u003eMedicinal Biology of Thrombosis and Hemostasis\u003c/em\u003e, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; has received personal fees from Novo Nordisk A/S.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTS:\u003c/strong\u003e Is a member of the \u003cem\u003eMedicinal Biology of Thrombosis and Hemostasis\u003c/em\u003e, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSH:\u003c/strong\u003e Is a member of the \u003cem\u003eMedicinal Biology of Thrombosis and Hemostasis\u003c/em\u003e, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; owns stock in Chugai Pharmaceutical Co., Ltd.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNS:\u003c/strong\u003e Reports no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYI:\u003c/strong\u003e Has received specific clinical trial funding from MediaMart Co., Ltd.; has received research funding from Chugai Pharmaceutical Co., Ltd., Johnson \u0026amp; Johnson K.K., KM Biologics, Olympus Terumo Biomaterials Corp., and Zimmer Biomet; has received honoraria from Asahi Kasei Pharma Corporation, Bayer Yakuhin Ltd., Chugai Pharmaceutical Co., Ltd., CSL Behring, Healios K.K., Hisamitsu Pharmaceutical Co., Johnson \u0026amp; Johnson K.K., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Sanofi K.K., and Takeda Pharmaceutical Co., Ltd.; and serves as a medical advisor for Chugai Pharmaceutical Co., Ltd. and KM Biologics.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAK:\u003c/strong\u003e Has received grants or research support from Chugai Pharmaceutical Co., Ltd.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eKN:\u003c/strong\u003e Is a member of the \u003cem\u003eMedicinal Biology of Thrombosis and Hemostasis\u003c/em\u003e, established by Nara Medical University and Chugai Pharmaceutical Co., Ltd.; has received grants, personal fees, and nonfinancial support from Chugai Pharmaceutical Co., Ltd.; personal fees from F. Hoffmann-La Roche Ltd.; has received grants, personal fees, and nonfinancial support from Sysmex Co.; has received grants and personal fees from Takeda Pharmaceutical Co.; has received grants and personal fees from Sanofi S.A.; has received personal fees from CSL Behring Co.; has received grants and personal fees from KM Biologics Co.; grants and personal fees from Novo Nordisk A/S; has received grants and personal fees from Bayer AG; has received grants and personal fees from Bioverativ Inc.; has received grants and personal fees from Shire Plc; and is a coinventor of a patent related to an anti-FIXa/FX bispecific antibody.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChugai Pharmaceutical Co., Ltd.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthors\u0026rsquo; contributions\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: YM, MS, NM, AS, RK, KT, TS, SH, and KN.\u003c/p\u003e\n\u003cp\u003eData curation: YM, MS, NM, AS, NS, YI, AK, and KN.\u003c/p\u003e\n\u003cp\u003eFormal analysis: YM, MS, NM, AS, RK, KT, TS, SH, and KN.\u003c/p\u003e\n\u003cp\u003eInvestigation: YM, MS AS, KT, NS, YI, AK, and KN.\u003c/p\u003e\n\u003cp\u003eMethodology: YM, MS, NM, AS, RK, KT, TS, SH, and KN.\u003c/p\u003e\n\u003cp\u003eProject administration: YM, MS, NM, AS, RK, KT, TS, SH, and KN.\u003c/p\u003e\n\u003cp\u003eResources: YM, MS, AS, KT, NS, AK, and KN.\u003c/p\u003e\n\u003cp\u003eSupervision: YM, MS, and KN.\u003c/p\u003e\n\u003cp\u003eVisualization: YM, MS, NM, AS, RK, KT, TS, SH, and KN.\u003c/p\u003e\n\u003cp\u003eWriting -original draft: All the authors.\u003c/p\u003e\n\u003cp\u003eWriting -review and editing: All the authors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the participants who were involved in the measurements. We thank American Journal Experts (AJE) for their help with English language editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSrivastava A, Santagostino E, Dougall A, Kitchen S, Sutherland M, Pipe SW, et al. WFH guidelines for the management of hemophilia, 3rd edition. Haemophilia. 2020;26:1-158.\u003c/li\u003e\n\u003cli\u003eKnobe K, Berntorp E. Haemophilia and joint disease: pathophysiology, evaluation, and management. J Comorb. 2011;1:51-9.\u003c/li\u003e\n\u003cli\u003eRiley RR, Witkop M, Hellman E, Akins S. Assessment and management of pain in haemophilia patients. Haemophilia. 2011;17:839-45.\u003c/li\u003e\n\u003cli\u003eWitkop M, Neff A, Buckner TW, Wang M, Batt K, Kessler CM, et al. Self-reported prevalence, description and management of pain in adults with haemophilia: methods, demographics and results from the pain, functional impairment, and quality of life (P-FiQ) study. Haemophilia. 2017;23:556-65.\u003c/li\u003e\n\u003cli\u003eStromer W, Pabinger I, Ay C, Crevenna R, Donnerer J, Feistritzer C, et al. Pain management in hemophilia: expert recommendations. Wien Klin Wochenschr. 2021;133:1042-56.\u003c/li\u003e\n\u003cli\u003eManco-Johnson MJ, Soucie JM, Gill JC. Prophylaxis usage, bleeding rates, and joint outcomes of hemophilia, 1999 to 2010: a surveillance project. Blood. 2017;129:2368-74.\u003c/li\u003e\n\u003cli\u003eStrike K, Mulder K, Michael R. Exercise for haemophilia. Cochrane Database Syst Rev. 2016;12:CD011180.\u003c/li\u003e\n\u003cli\u003eMawarikado Y, Sakata A, Inagaki Y, Harada S, Tatsumi K, Matsumoto N, et al. Force-sensing treadmill gait analysis system can detect gait abnormalities in haemophilia patients without arthropathy. Haemophilia. 2024;30:780-90.\u003c/li\u003e\n\u003cli\u003ePutz P, Klinger M, Male C, Pabinger I. Lower physical activity and altered body composition in patients with haemophilia compared with healthy controls. Haemophilia. 2021;27:e260-6.\u003c/li\u003e\n\u003cli\u003eBuxbaum NP, Ponce M, Saidi P, Michaels LA. Psychosocial correlates of physical activity in adolescents with haemophilia. Haemophilia. 2010;16:656-61.\u003c/li\u003e\n\u003cli\u003eWalker RG, Obeid J, Nguyen T, Ploeger H, Proudfoot NA, Bos C, et al. Sedentary time and screen-based sedentary behaviors of children with a chronic disease. Pediatr Exerc Sci. 2015;27:219-25.\u003c/li\u003e\n\u003cli\u003eArnold WD, Hilgartner MW. Hemophilic arthropathy. Current concepts of pathogenesis and management. J Bone Joint Surg Am. 1977;59:287-305.\u003c/li\u003e\n\u003cli\u003eSasaki JE, John D, Freedson PS. Validation and comparison of ActiGraph activity monitors. J Sci Med Sport. 2011;14:411-6.\u003c/li\u003e\n\u003cli\u003eKennedy M, O\u0026apos;Gorman P, Monaghan A, Lavin M, O\u0026apos;Mahony B, O\u0026apos;Connell NM, et al. A systematic review of physical activity in people with haemophilia and its relationship with bleeding phenotype and treatment regimen. Haemophilia. 2021;27:544-62.\u003c/li\u003e\n\u003cli\u003ePiercy KL, Troiano RP, Ballard RM, Carlson SA, Fulton JE, Galuska DA, et al. The physical activity guidelines for Americans. JAMA. 2018;320:2020-8.\u003c/li\u003e\n\u003cli\u003eCruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruy\u0026egrave;re O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48:601.\u003c/li\u003e\n\u003cli\u003eOldenburg J, Mahlangu JN, Kim B, Schmitt C, Callaghan MU, Young G, et al. Emicizumab prophylaxis in hemophilia a with inhibitors. N Engl J Med. 2017;377:809-18.\u003c/li\u003e\n\u003cli\u003eB\u0026eacute;rub\u0026eacute; S, Ogez D, Aramideh J, Amesse C, Bourque CJ, Longpr\u0026eacute; C, et al. It\u0026apos;s difficult to say no: development of a parenting booklet about physical activity restrictions and recommendations in pediatric hemophilia. Health Psychol Open. 2021;8:20551029211039920.\u003c/li\u003e\n\u003cli\u003eGoto M, Takedani H, Yokota K, Haga N. Strategies to encourage physical activity in patients with hemophilia to improve quality of life. J Blood Med. 2016;7:85-98.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"thrombosis-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"thrj","sideBox":"Learn more about [Thrombosis Journal](http://thrombosisjournal.biomedcentral.com/)","snPcode":"12959","submissionUrl":"https://submission.nature.com/new-submission/12959/3","title":"Thrombosis Journal","twitterHandle":"@Thrombosis_J","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"haemophilia A, haemophilia B, joint diseases","lastPublishedDoi":"10.21203/rs.3.rs-8217815/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8217815/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eIn haemophilia, recurrent joint bleeding often results in joint destruction, which in turn leads to reduced physical activity (PA) and decreased quality of life (QOL). While maintaining high PA levels is important in the care of people with haemophilia (PwH), it remains unclear whether PwH without joint disease can maintain adequate activity levels.\u003c/p\u003e\u003ch2\u003eAim\u003c/h2\u003e\u003cp\u003eThis descriptive cross-sectional study sought to compare moderate-to-vigorous physical activity (MVPA) levels among PwH with haemophilic arthropathy (HA), PwH without HA, and non-PwH.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA total of 46 males wore a triaxial accelerometer (wGT3X-BT, ActiGraph) during daily activities for seven consecutive days. A bout of MVPA was defined as at least 10 consecutive minutes of moderate-intensity or higher activity. MVPA was assessed as the percentage of wear time during MVPA and the total number of MVPA bouts.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eBoth PwH groups demonstrated significantly lower MVPA percentages and fewer MVPA bouts than the controls (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). No MVPA bouts were recorded among 52.6% of PwH with HA versus 25% of PwH without HA. No significant differences were observed in sedentary or light activity between the PwH groups.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003ePA levels were significantly reduced in PwH, regardless of joint status, suggesting that factors beyond joint damage, such as fear of bleeding or behavioural avoidance, may play a role. These findings highlight the need for individualized, evidence-based interventions to safely promote physical activity and improve long-term health outcomes in PwH.\u003c/p\u003e","manuscriptTitle":"Physical activity patterns in people with haemophilia with and without arthropathy: A cross-sectional study using wearable sensors","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-05 11:12:45","doi":"10.21203/rs.3.rs-8217815/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-19T09:18:08+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-10T11:31:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"130149067064612413701307053891552896461","date":"2025-12-08T09:08:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"306265185644102974234364226534053804233","date":"2025-12-03T17:43:11+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-01T16:06:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"246737084267638800172389742822499388111","date":"2025-12-01T14:47:32+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-01T10:11:33+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-27T22:49:26+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-27T22:48:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"Thrombosis Journal","date":"2025-11-27T04:24:10+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"thrombosis-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"thrj","sideBox":"Learn more about [Thrombosis Journal](http://thrombosisjournal.biomedcentral.com/)","snPcode":"12959","submissionUrl":"https://submission.nature.com/new-submission/12959/3","title":"Thrombosis Journal","twitterHandle":"@Thrombosis_J","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5dc50d9c-d8e1-40f0-a352-eab8dce4fc77","owner":[],"postedDate":"December 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-28T03:24:37+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-05 11:12:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8217815","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8217815","identity":"rs-8217815","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}