Ultrasound abnormalities were found during routine evaluation of joints in children with haemophilia on prophylaxis. Most joints with ultrasound abnormalities showed low HJHS scores too. Ultrasound could be used to evaluate whether minimal losses of clinical function might be caused by anatomical changes.

Introduction Recurrent joint bleeding is the hallmark of haemophilia. Synovial hypertrophy observed with Magnetic Resonance Imaging (MRI) is associated with an increased risk of future joint bleeding. Aim The aim of this study was to investigate whether point‐of‐care ultrasound (POC‐US) is an accurate alternative for MRI for the detection of early joint changes. Methods In this single centre diagnostic accuracy study, bilateral knees and ankles of haemophilia patients with no or minimal arthropathy on X‐rays were scanned using POC‐US and 3 Tesla MRI. POC‐US was performed by 1 medical doctor, blinded for MRI, according to the “Haemophilia Early Arthropathy Detection with Ultrasound” (HEAD‐US) protocol. MRIs were independently scored by 2 radiologists, blinded for clinical data and ultrasound results. Diagnostic accuracy parameters were calculated with 95% confidence intervals (CI). Results Knees and ankles of 24 haemophilia patients (96 joints), aged 18‐34, were studied. Synovial hypertrophy on MRI was observed in 20% of joints. POC‐US for synovial tissue was correct (overall accuracy) in 97% (CI: 91‐99) with a positive predictive value of 94% (CI: 73‐100) and a negative predictive value of 97% (CI: 91‐100). The overall accuracy of POC‐US for cartilage abnormalities was 91% (CI: 83‐96) and for bone surface irregularities 97% (CI: 91‐99). Conclusion POC‐US could accurately assess synovial hypertrophy, bone surface irregularities and cartilage abnormalities in haemophilia patients with limited joint disease. As POC‐US is an accurate and available alternative for MRI, it can be used for routine evaluation of early joint changes.

Prophylaxis is the recommended treatment for children with severe haemophilia A, but whether prophylaxis should be continued in adulthood is still under debate. Previous studies with limited follow-up have suggested that some patients may be able to stop prophylaxis in adulthood, while maintaining good joint health. This single-centre observational cohort study examined patients with severe haemophilia A born 1970-1988 without inhibitor development, and assessed the long-term consequences of discontinuing prophylaxis. Patient-initiated changes in prophylaxis, including all switches to on-demand treatment lasting a minimum of two consecutive weeks, were recorded from the time self-infusion began until the last evaluation. Sixty-six patients were evaluated at a median age of 32.4 years: 26 % of patients had stopped prophylaxis for a median of 10 years, 15 % had interrupted prophylaxis and 59 % had continued prophylaxis. Annual joint bleeding rate (AJBR), Haemophilia Joint Health Score (HJHS-2.1; 0-124 points), radiological Pettersson score (0-78 points) and Haemophilia Activities List score (HAL; 100-0 points) were compared between patients who stopped and patients who continued prophylaxis. Although self-reported bleeding rates and functional limitations were similar in both groups (AJBR: 1.5 vs 1.2 and HAL: 84 vs 84 for those who stopped and continued prophylaxis, respectively), objective assessment of joint status showed increased arthropathy after 10 years of on-demand treatment in patients who stopped prophylaxis compared with those who continued (HJHS: 23 vs. 14 and Pettersson: 16 vs 5, respectively; P< 0.01). These results support continuation of long-term prophylaxis in adults and demonstrate the need for objective monitoring of joint status.

Joint bleeds in patients with haemophilia cause synovial hypertrophy and direct blood-related osteochondral changes. The ankles, knees and elbows are the most affected joints. To assess osteochondral changes in these joints, the radiologic Pettersson Score [1] and the clinical Gilbert Score [2] were developed. With the use of prophylactic replacement therapy the emphasis is on prevention of joint changes. As both scores are unable to detect early joint changes, the Gilbert score was further developed into the more sensitive Haemophilia Joint Health Score (HJHS) (2006) [3] and haemophilia-specific ultrasound protocols were introduced to assess synovial hypertrophy and cartilage defects. The 'Haemophlia Early Arthropathy Detection with UltraSound' (HEAD-US) protocol has been developed for non-radiologists, enabling direct assessment of joint health in conjunction with history taking and physical examination [4].Discrepancies between clinical function and imaging of haemophilia arthropathy (HA) are well known. In children with moderate or severe haemophilia on prophylaxis, routine ultrasound examination according to the HEAD-US protocol has shown to be able to detect osteochondral changes in joints without abnormalities on the HJHS and to evaluate whether minimal findings might be caused by osteochondral changes [5]. Yet, in adults, the value of HEAD-US in addition to HJHS has not yet been reported. The aim of this study is to explore the added value of routine HEAD-US examination after HJHS examination in adults with haemophilia.A retrospective cohort study was conducted using medical health records of adult patients with haemophilia collected during multidisciplinary check-up visits at the van Creveldkliniek at University Medical Center Utrecht between June 2015 and September 2015. Patients were excluded if they were wheelchair dependent, had a joint or muscle bleed <6 weeks prior to the assessment or underwent orthopaedic surgery <24 months prior to the assessment. No restrictions were made for severity of haemophilia. The study was approved by the Institutional Review Board of the University Medical Center Utrecht, The Netherlands.During the check-ups, both elbows, knees and ankles were examined according to the HJHS version 2.1 by a single physiotherapist (MT) with extensive experience with the HJHS. For each joint swelling (0-3), duration of swelling (0-1), atrophy (0-2), crepitus (0-2), range of motion (ROM) (flexion 0-3; extension 0-3), strength (0-4) and pain (0-2) were evaluated, adding up to a score between 0 and 20 per joint. Higher scores indicate worse joint function. Directly after HJHS examination, HEAD-US assessment was performed by one medical doctor (WF) [4]. The operator was trained according to the formal HEAD-US courses, including one initial training and two advanced HEAD-US courses. The HEAD-US protocol allows for the assessment and scoring regarding the degree of synovial hypertrophy (0-2), cartilage damage (0-4) and abnormalities of subchondral bone (0-2). Possible scores range from 0 to 8...

Patients with severe von Willebrand disease (VWD) may develop arthropathy after joint bleeds. Information on its prevalence and severity is limited. We aimed to assess the occurrence and severity of arthropathy in VWD and its impact on daily life. VWD patients with and without verified joint bleeds were matched for age, sex and Factor VIII level or von Willebrand Factor activity in a nested case-control study within the Willebrand in the Netherlands study. Assessments included the Hemophilia Joint Health Score (0–124), Pettersson score (0–13 per joint X-ray), Hemophilia Activity List score (0–100), joint pain (Visual Analog Scale 0–10), and the Impact on Participation and Autonomy questionnaire (0–20). Arthropathy was defined as a Hemophilia Joint Health Score of 10 or higher, or a Pettersson score over 3 of at least one joint. We included 48 patients with verified joint bleeds (cases) and 48 controls: 60% males, mean age 46 years (range 18–80), median von Willebrand Factor activity 5 versus 8 IU/dL and Factor VIII 24 versus 36 IU/dL. Arthropathy occurred in 40% of the cases versus 10% of the controls (P<0.01). The cases reported more functional limitations compared to the controls (median Hemophilia Activity List score: 88 vs. 100, P<0.01). Arthropathy was related to joint pain and less social participation (Visual Analog Scale>3: 13 of 19 vs. 3 of 28, P<0.01, and median score on the participation questionnaire 6.1 vs. 0.9, P<0.01). In conclusion, arthropathy occurs in 40% of VWD patients after joint bleeds and is associated with pain, radiological abnormalities, functional limitations, and less social participation (Dutch trial register: NTR4548).

Magnetic resonance imaging (MRI) is considered as the reference standard to assess early joint changes in hemophilia. However, the clinical relevance of MRI findings is still unknown. The aim of this prospective study was to assess the predictive value of MRI for 5-year joint bleeding and progression of arthropathy in patients with hemophilia. Both knees and ankles of patients with hemophilia and absent or limited arthropathy on radiographs were assessed by using MRI and radiographs. MRI scans were scored according to the International Prophylaxis Study Group MRI score for hemophilic arthropathy. Patients were followed up for 5 years, including assessment of joint bleeding and repeated radiographic assessment. Associations between baseline MRI findings with 5-year bleeding and progression of arthropathy were expressed as odds ratios (OR), adjusted for severity of disease and joint bleeding history. Baseline assessment included 104 joints of 26 patients with hemophilia (median age, 21 years). Four ankles with severe joint changes were excluded. Follow-up was available for 96 (92%) of 104 joints. During 5 years of follow-up, bleeding was reported for 36% of joints. Five-year bleeding was significantly increased in joints with synovial hypertrophy at 80% vs 27% in joints without synovial hypertrophy (OR, 10.1; 95% confidence interval, 3.4-31.3). In joints with normal baseline radiographs, any osteochondral or synovial changes on MRI were associated with radiographic changes 5 years later (positive predictive value, 75%; negative predictive value, 98%). Joints with synovial hypertrophy on MRI had a significantly higher chance of 5-year bleeding. All MRI changes, except effusion, were strong predictors for development of arthropathy on radiographs.

To evaluate outcome of prophylactic clotting factor replacement in children with haemophilia, the Haemophilia Joint Health Score (HJHS) was developed aiming at scoring early joint changes in children aged 4-18. The HJHS has been used for adults on long-term prophylaxis but interpretation of small changes remains difficult. Some changes in these patients may be due to sports-related injuries. Evaluation of HJHS score in healthy adults playing sports could improve the interpretation of this score in haemophilic patients. The aim of this study was to evaluate the HJHS scores in a cohort of young, healthy men participating in sports. Concomitant with a project collecting MRI images of ankles and knees in normal young adults, HJHS scores were assessed in 30 healthy men aged 18-26, participating in sports one to three times per week. One physiotherapist assessed their clinical function using the HJHS 2.1. History of joint injuries was documented. MRI images were scored by a single radiologist, using the International Prophylaxis Study Group additive MRI score. Median age of the study group was 24.3 years (range 19.0-26.4) and median frequency of sports activities was three times per week (range 1-4). Six joints (five knees, one ankle) had a history of sports-related injury. The median overall HJHS score was 0 out of 124 (range 0-3), with 60% of subjects showing no abnormalities on HJHS. All joints were normal on MRI. These results suggest that frequent sports participation and related injuries are not related with abnormalities in HJHS scores.

This study evaluated the accuracy of synthetic computed tomography (sCT), as compared to CT, for the 3D assessment of the hip morphology. Thirty male patients with asymptomatic hips, referred for magnetic resonance (MR) imaging and CT, were included in this retrospective study. sCT images were generated from threedimensional radiofrequency-spoiled T1-weighted multi-echo gradient-echo MR images using a commercially available deep learning-enabled software and were compared with CT images through mean error and surface distance computation and by means of eight clinical morphometric parameters relevant for hip care.Parameters included center-edge angle (CEA), sharp angle, acetabular index, extrusion index, femoral head center-to-midline distance, acetabular version (AV), and anterior and posterior acetabular sector angles. They were measured by two senior orthopedic surgeons and a radiologist in-training on CT and sCT images. The reliability and agreement of CT-and sCT-based measurements were assessed using intraclass correlation coefficients (ICCs) for absolute agreement, Bland-Altman plots, and two one-sided tests for equivalence. The surface distance between CTand sCT-based bone models were on average submillimeter. CT-and sCT-based measurements showed moderate to excellent interobserver and intraobserver correlation (0.56 < ICC < 0.99). In particular, the inter/intraobserver agreements were good for AV (ICC > 0.75). For CEA, the intraobserver agreement was good (ICC > 0.75) and the interobserver agreement was moderate (ICC > 0.69). Limits of agreements were similar between intraobserver CT and intermodal measurements.All measurements were found statistically equivalent, with average intermodal differences within the intraobserver limits of agreement. In conclusion, sCT and CT were equivalent for the assessment of the hip joint bone morphology.