Objectives Musculoskeletal ultrasound (US) is used increasingly to examine hemophilic arthropathy. However, quantitative algorithms to document findings are lacking. We developed and sought to validate a protocol quantifying hemophilic joint abnormalities. Methods Thirty‐one patients with hemophilia were examined serially for 2 years with musculoskeletal US (≈600 joint examinations and ≈6000 images). Based on the spectrum of pathologies, a quantitative algorithm, named Joint Tissue Activity and Damage Examination (JADE), was developed for soft tissue and osteochondral measurements, including power Doppler, using nominal group techniques. To study intra‐ and inter‐rater reliability, 8 musculoskeletal US–experienced hemophilia providers performed anatomic landmark recognition and tissue measurements on 86 images with arthropathic changes, with repetition 1 month later. Twenty‐three musculoskeletal US–inexperienced providers performed similar assessments. Inter‐operator reliability was established by 6 musculoskeletal US–experienced hemophilia providers, each acquiring images and JADE assessments of 3 hemophilic arthropathic joints. A radiologist and musculoskeletal sonographer functioned as adjudicators. The statistical analysis was performed with the intraclass correlation coefficient (ICC), Fleiss κ, and Cohen κ where appropriate. Results The musculoskeletal US–experienced providers showed excellent intra‐and inter‐rater reliability for tissue measurements (ICCs, 0.94–0.96). Agreement was good to excellent for landmark recognition (Fleiss κ, 0.87‐0.94). Inter‐operator reliability was excellent for measurements and landmark recognition (ICC, 0.90; Fleiss κ, 1.0). Agreement with adjudicators was mostly good to excellent. Musculoskeletal US–inexperienced providers showed excellent inter‐rater reliability for measurements (ICC, 0.96) and moderate agreement for landmark recognition (Fleiss κ, 0.58). Conclusions The JADE protocol appears feasible for quantifying hemophilic intra‐articular abnormalities. Musculoskeletal US–trained hemophilia providers showed high intra‐rater, inter‐rater, and inter‐operator reliability, supporting JADE as a protocol for clinical management and research.

Introduction Point-of-care (POC) musculoskeletal ultrasound (MSKUS) is increasingly used by hemophilia providers to guide management, however, pathologic tissue differentiation with US is uncertain. We sought to determine the extent to which POC MSKUS can identify and discriminate pathologic soft tissue changes in hemophilic arthropathy. Materials and Methods 36 adult patients with hemophilia A/B were prospectively enrolled. POC MSKUS was performed on arthropathic joints (16 knees, 10 ankles, and 10 elbows) using standard views by a MSKUS-trained and certified hematologist, who recorded abnormal intra-articular soft tissue accumulation. Within three days, magnetic resonance imaging (MRI) was performed using conventional and multi-echo ultrashort echo time (UTE) sequences. Soft tissue identification (synovial proliferation with or without hemosiderin, fat, and/or blood products) was performed by a musculoskeletal radiologist. Findings obtained with both imaging modalities were compared and correlated in a blinded fashion. Results There was perfect agreement between the modalities on the presence of abnormal soft tissue (34/36 cases). However, MSKUS was unable to discriminate between coagulated blood, synovium, intra- or extra-synovial fat tissue, or hemosiderin deposits due to wide variation in echogenicity. Conclusion MSKUS is valuable for POC imaging to determine the presence of soft tissue accumulation in discrete areas. However, due to limitations in MSKUS in discriminating the nature of pathological soft tissues and detecting hemosiderin, MRI will be required if such discrimination is clinically important.

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Introduction Haemophilia patients experience painful joint episodes which may or may not be associated with haemarthrosis. We sought to validate a questionnaire developed by the Canadian Haemophilia Society using point‐of‐care musculoskeletal ultrasound (POC MSKUS) to confirm haemarthrosis. Methods The questionnaire comprised of 20 questions (10 each associated with haemarthrosis and arthritis pain) and was administered to adult haemophilia patients reporting to the Haemophilia Treatment Centre (University of California San Diego). We confirmed the presence (or absence) of haemarthrosis using POC MSKUS [Joint Activity and Damage Exam (JADE)]. We fitted univariate and multivariate generalized estimating equations to identify symptoms associated with haemarthrosis. Results We evaluated 79 painful episodes in 32 patients [median age = 38 years (range 21–74)]. POC MSKUS detected haemarthrosis in 36 (46%) episodes. The strongest predictor for haemarthrosis pain was ‘like a balloon swelling with water’ (odds ratio [OR] 2.88 [CI .68;12.10]); ‘no feeling of sponginess with movement’ (OR .24[CI .07;.76]) was the strongest for arthritic pain. We identified four questions with the strongest OR for differentiating haemarthrosis pain from arthritic pain to develop an algorithm for haemarthrosis prediction. Answering these questions in “yes/no” fashion yielded estimates of the probability of haemarthrosis Conclusion Objective diagnosis of haemarthrosis by MSKUS facilitated the development of a symptom‐based prediction tool for diagnosis of haemarthrosis. The tool requires further validation and will be particularly helpful in situations where MSKUS is not readily available.

Background: Low impact physical activity is important for patients with haemophilic arthropathies, but is often considered boring with suboptimal adherence. There is therefore a need for physical activities that motivate patient engagement. Aims: To evaluate the benefits of top rope climbing, increasingly used in other musculoskeletal disorders, as an engaging sports discipline in haemophilia. Materials/Methods: Six adult arthropathic patients with haemophilia (PWH) completed 12 sessions of tailored top rope climbing training. Functional and clinical joint status, climbing skills, quality of life (QoL), annual bleed rate (ABR) and joint findings with musculoskeletal ultrasound/power doppler (MSKUS/PD) were assessed before and after climbing. Results: Haemophilia joint health scores, dorsiflexion in arthropathic joints and climbing skills all improved. ABRs were comparable before and during climbing, and QoL remained high. MSKUS evaluation demonstrated no detrimental effects on synovial and cartilage health, with a decrease of inflammatory PD signal in some joints. Conclusion: We conclude that top rope climbing therapy (known as “Haemophilia Vertical”) can improve joint health in PWH with arthropathies. Haemophilia Vertical therefore emerges as an innovative athletic concept to promote physical activity among PWH. Further study investigating the longer-term impact in a larger cohort is warranted.

Background The use of musculoskeletal ultrasound (MSKUS) for point-of-care (POC) evaluation of hemophilic arthropathy is growing rapidly. However, the extent to which MSKUS influences clinical treatment decisions is unknown. Methods We conducted a three-year, prospective, multi-center study at three hemophilia treatment centers in the United States to evaluate the utilization of POC-MSKUS for routine clinical decision-making in adult persons with hemophilic arthropathy. Bilateral elbows, knees and ankles were assessed clinically [Hemophilia Joint Health Score (HJHS)] and with POC-MSKUS by the Joint TissueActivity and Damage Exam (JADE) protocol at baseline and approximately annually for two additional times. Treatment decisions, including physical therapy (PT) and “medical” (joint injections/aspirations, referrals to orthopedics, changes/adjustments of hemostatic plans, and use of oral anti-inflammatory medications) were recorded in relation to POC-MSKUS. Results Forty-four persons [median age 37 years (IQR 29, 51)], mostly with severe Hemophilia A on clotting factor prophylaxis, completed 129 visits, yielding 792 joint exams by POC-MSKUS and HJHS [median at baseline 27 (IQR 18, 42)] over a median follow up of 584 days (range: 363 to 1072). Among 157 management decisions, 70% were related to PT plans (n = 110) and 30% were “medical”. Point-of-care MSKUS influenced 47/110 (43%) PT plans, mostly informing treatment of specific arthropathic joints (45/47 plans) in patients with high HJHS. Physical therapy plans influenced by POC-MSKUS directed more manual therapy/therapeutic exercises, while plans based on physical exam were focused more on global exercises and wellness. Treatment decisions were mostly based on the identification of specific musculoskeletal abnormalities visualized by POC-MSKUS. Of note 20/47 (43%) POC-MSKUS plans included de-escalation strategies, thereby reducing exercise intensity, mostly for joint instability and subclinical hemarthroses. Point-of-care MSKUS also informed 68% (32/47) of “medical” decisions, surprisingly mostly for injections/aspirations and referrals to orthopedics, and not for adjustments of hemostatic treatment. Although not formally studied, ultrasound images were used frequently for patient education. Conclusion Routine joint evaluations with POC-MSKUS resulted in few changes regarding medical management decisions but had a profound effect on the formulation of PT plans. Based on these findings, new studies are essential to determine the benefit of MSKUS-informed management plans on joint health outcomes.

Introduction Musculoskeletal ultrasound (MSKUS) is being used increasingly for point-of-care (POC) assessment of painful hemophilic joints and has proven to be a critical tool in the evaluation of the presence of hemarthrosis. To date, MSKUS examinations are exclusively performed in the clinic, which often results in delays to definitive diagnosis since patients and caregivers are not always able to undergo or perform a clinical assessment at the time of the event. The use of pocket handheld ultrasound devices, which have primarily been applied for cardiopulmonary and abdominal POC bedside assessments, offers a promising solution to this problem by enabling patients and remote clinics to acquire images for off-site real-time evaluations via tele-transmission. In this study, we evaluated the extent to which the quality of images generated by the handheld ultrasound devices compared to stationary MSKUS and if the image interpretation was similar between various health care providers. The aim is to establish the dynamic potential of this pocket sized device as a cost effective and comparable alternative to the stationary MSKUS. Methods A total of 72 typical joint views (36 of the knee, 20 of the elbow and 16 of the ankle) were acquired from healthy volunteers and hemophilia patients at the same session with the stationary GE LogiqS8 and the handheld GE V2scan. Ten different health care providers (7 physicians, 2 physical therapists and 1 nurse), all trained at least in the CME-accredited MSKUS course at the University of California, San Diego, (UCSD), reviewed these images side by side. Information about view, probe placement and tissue compressibility to identify effusions was provided. Each subject was asked to evaluate the following characteristics on a graded scale: (1) similarity of the handheld image to the GE LogiqS8 image, (2) their confidence in identification of major landmarks on the handheld image compared to the GE LogiqS8 image and if an effusion was present, (3) their ability to identify the effusion on both images. The adjudicators were a board-certified radiologist and a senior hematologist trained and experienced in MSKUS. Study procedures complied with rules set forth by the UCSD Human Research Protection Program. Results A total of 720 responses were analyzed from the images of normal and hemophilic joints. Among the responses, 87% of images were rated as at least moderately similar to very similar between the handheld device and the stationary ultrasound. In terms of identification, 88% of the responses were rated as at least moderately confident to very confident in the identification of major landmarks on the handheld image. Among a total of 170 responses for effusions, 87% of effusions were identified with both the handheld device and the stationary MSKUS (Table). These percentages were consistent between the different joints with slightly higher rates of correct identification on the handheld device noted in the knee where 100% of effusions were recognized correctly. Representative images depicting an effusion in the lateral recess of the knee acquired simultaneously with the handheld GE V2scan and stationary MSKUS is provided (Figure). There was no significant discrepancy of answers between the types of providers. Conclusion The image quality of the handheld pocket device (GE V2 scan) was sufficient to determine major landmarks in joints and to diagnose effusions, with image interpretation comparable between the various health care providers encompassing physicians, nurses, and physical therapists. These findings highlight the potential in the application of this device as a novel POC modality for both patient-performed tele-ultrasound or tele-ultrasound use in remote, resource limited regions for real-time assessments of hemarthrosis. While encouraging, these observations need to be further validated and extended more broadly in future studies. Table Table. Disclosures Kruse-Jarres: Baxalta: Consultancy, Honoraria; Grifols: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; CSL Behring: Consultancy, Honoraria; Bayer: Consultancy, Honoraria. Quon:Bayer: Consultancy; Biogen: Consultancy, Speakers Bureau; Grifols: Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau. von Drygalski:Pfizer: Consultancy, Honoraria, Speakers Bureau; Hematherix LLC: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Honoraria, Speakers Bureau; CSL-Behring: Consultancy, Honoraria, Speakers Bureau; Biogen: Consultancy, Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Baxalta/Shire: Consultancy, Honoraria, Speakers Bureau.

Background: Hemophilia is a bleeding disorder associated with frequent hemarthroses and ensuing debilitating arthropathies. Patients with hemophilia (PWH) are encouraged to participate in low impact physical activities to improve joint health, mobility, and quality of life (QoL). However, activities such as walking, swimming or physical therapy are often perceived as "boring", which results in participation in high risk activities that may cause injury or bleeding. Indoor therapeutic rock climbing is practiced successfully to improve physical and psychological well-being in patients with neuromuscular disorders, and may be a "fun" alternative for PWH. The aim of this study was to investigate the safety of therapeutic rock climbing and its effects on joint health for PWH with arthropathies. Methods: Twelve adult male patients (median age 31 years, IQR=24,41) with moderate to severe hemophilia A and arthropathies (defined by decreased normative range of motion (ROM)) were recruited from the Hemophilia Treatment Centers at University of California, San Diego, USA (UCSD) and Ludwig Maximilians University, Munich, Germany (LMU)). All participants completed 12 sessions of individually tailored indoor top rope rock climbing, instructed by a climbing coach and physical therapist. Functional and clinical joint status including ROM, Hemophilia Joint Health Score (HJHS) for elbows, knees, and ankles (n=12), climbing skills (UCSD: Yosemite Decimal Scale; LMU: Union Internationale des Associations d'Alpinisme scale), QoL measures (UCSD: Haem-A-Qol, Hep-Test-Q; LMU: Hemo-Qol-A), annual bleed rate (ABR), and clotting factor consumption were assessed in both cohorts (UCSD n=6; LMU n=6) pre and post climbing. Additionally, effects on cartilage health, joint inflammation and soft tissue hypertrophy were assessed by musculoskeletal ultrasound and power doppler (MSKUS/PD) in the UCSD cohort. Descriptive statistics and Wilcoxon matched-pairs signed-rank tests were used for data analysis. Data are expressed as median and inter-quartile range; p-values ≤ 0.05 were considered significant. Results: Compared to baseline, HJHS improved significantly after completion of the program (16.5 [IQR=6.0, 28.5] post vs 17.5 [6.0, 35.0] pre; n=12; p = 0.03). A significant increase in dorsiflexion was evident in arthropathic ankles (0 degrees [IQR= -4, 4] post vs -4 [IQR-10, -3] pre; n = 9; p<0.01), with trends towards increased ROM in arthropathic elbows and knees. All subjects advanced their climbing skills significantly (UCSD: 4 levels; LMU: 3 levels; both p-values =0.03). ABRs and clotting factor consumption were comparable before and during the climbing program for the UCSD cohort, whereas ABRs improved slightly in the LMU cohort in conjunction with pharmacokinetic tailored clotting factor therapy. Pre and post ABRs were 1 [IQR=0,4] and 0 [IQR=0,4] for the UCSD cohort (p = 1.00), and 5.5[IQR=1,8] and 1.7[IQR=0,2.3] for the LMU cohort (p=0.09), respectively. Clotting factor usage during climbing was similar between the 2 cohorts (UCSD 499 [IQR=298,593] U/kg/month; LMU 355 [IQR=250,490] U/kg/month, p = 0.39). Climbing resulted in significantly improved QoL in the LMU cohort (25.9 [IQR=21.4,30.0] points post vs 25.2 [IQR=21.0, 28.6] pre; n=6; p=0.05), but remained unchanged for the UCSD participants (p=0.31), possibly because of high QoL at outset. However, all UCSD participants voiced a meaningful increase of well-being and new confidence to overcome challenges. MSKUS/PD examinations of arthropathic joints revealed no negative effects on cartilage or soft tissue health, and demonstrated decreased inflammation. Conclusions:Therapeutic rock climbing is not only safe but improves joint health and well-being in PWH with advanced arthropathies without triggering excessive clotting factor consumption. "Hemophilia Vertical" is an innovative athletic concept without the "boring" stigma of other low impact sports, and should be promoted to advance athletic hemophilia care concepts. Disclosures von Drygalski: Pfizer: Consultancy, Honoraria, Speakers Bureau; Biogen: Consultancy, Honoraria, Speakers Bureau; CSL-Behring: Consultancy, Honoraria, Speakers Bureau; Novo Nordisk: Consultancy, Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Baxalta/Shire: Consultancy, Honoraria, Speakers Bureau; Hematherix LLC: Membership on an entity's Board of Directors or advisory committees.