Merel A. Timmer

Introduction Recent recommendations of core outcome sets for haemophilia highlight the need for including measures of performance‐based physical health and physical function sustainability. To date, there is no consensus on what outcomes might be of value to clinicians and patients. Aim To identify instruments of performance‐based physical function to monitor musculoskeletal health in people with haemophilia that are practical in the clinical setting. Methods Utilising components from the Activities and Participation Category of the WHO International Classification of Functioning (WHO‐ICF), a consensus‐based, decision analysis approach was used to: identify activities people with haemophilia have most difficulty performing; identify quantitative performance‐based measures of identified activities via a scoping review; and obtain views on acceptability of the tests utilising a DELPHI approach. Results Eleven activities were identified: maintaining a standing position, walking long distances, walking up and down stairs, walking on different surfaces, running, hopping, jumping, squatting, kneeling, undertaking a complex lower limb task, undertaking a complex upper limb task. Following a 2‐round DELPHI survey of international physiotherapists, the 6‐min walk test, timed up and down stairs, 30‐s sit to stand, single leg stance, tandem stance, single hop for distance (children only) and timed up and go (adults only) reached consensus. Conclusion This study is the first step in defining a core set of performance‐based instruments to monitor physical health and sustainability of physical function outcomes in people with haemophilia. Establishing the psychometric properties of the instruments and whether they are meaningful to people with haemophilia is essential.

Aim Subclinical bleeding and inflammation play a role in progression of haemophilic arthropathy. Synovial proliferation is predictive of joint bleeding and its early detection may guide treatment changes and prevent arthropathy progression. This study evaluated the prevalence of active and inactive subclinical synovial proliferation and investigated potential biochemical blood/urine markers to identify patients with active subclinical synovial proliferation. Methods This cross‐sectional study included patients with severe haemophilia A born 1970–2006 who were evaluated during routine clinic visits. Patients with (a history of) inhibitors or recent joint bleeding were excluded. Elbows, knees and ankles were examined for subclinical synovial proliferation by ultrasound and physical examination. Active synovial proliferation was distinguished from inactive synovial proliferation using predefined criteria. Blood/urine biochemical markers (serum osteopontin, sVCAM‐1, Coll2‐1, COMP, CS846, TIMP, and urinary CTX‐II) were compared individually and as combined indexes between patients with and without active synovial proliferation. Results This cohort consisted of 79 patients with a median age of 31 years (range 16.5–50.8 years) with 62/79 (78%) of the patients using continuous prophylaxis. The annualized joint bleeding rate over the last 5 years was .6 (.2–1.1). Active (17/79, 22%) and inactive subclinical synovial proliferation (17/79, 22%) were both prevalent in this cohort. Biochemical markers were not correlated with active subclinical synovial proliferation. Conclusion Subclinical synovial proliferation, both active and inactive, was prevalent in patients with severe haemophilia A with access to prophylaxis and would be overlooked without routinely performed ultrasounds. Biochemical markers were unable to identify patients with active subclinical synovial proliferation.

Aim Traditionally, recovery after a joint bleed in people with bleeding disorders is evaluated by clinical symptoms. Following a bleed, however, asymptomatic joints may still show synovial hypertrophy and effusion on ultrasound. We evaluated the duration of full recovery from a joint bleed. Additionally, we determined how recovery differed when assessed by physical examination and ultrasound. Methods In this retrospective cohort study, we investigated joint bleeds in elbows, knees and ankles of people with haemophilia or Von Willebrand disease who attended the Van Creveldkliniek between 2016 and 2021. Physical examination (warmth, swelling, range of motion and gait) and ultrasound (effusion and synovial hypertrophy) were performed within 7 days after the onset of the bleed, 1 week after the first examination and monthly thereafter until patients had recovered fully. Joint bleeds were treated in line with the current international treatment guidelines. Results We evaluated 30 joint bleeds in 26 patients. The median recovery time was 1 month (range 0.3‐5 months). In 47% of the joint bleeds, the recovery took longer than 1 month. The moment of recovery based on physical examination and ultrasound differed in 27% of bleeds. Both persistent abnormalities at physical examination in joints with normalized ultrasounds and persistent ultrasound findings in clinically recovered joints occurred. Conclusion Joint bleed recovery can take long and recovery times differed per bleed. Recovery differed when assessed by physical examination or ultrasound. Therefore, both should be used to closely monitor recovery of joint bleeds and offer personalized care.

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

Introduction Ultrasound is increasingly used as addition to physical examination for detection of subclinical joint changes in haemophilia. However, the added value of ultrasound to physical examination for detecting synovial proliferation is not fully established. Aim To determine the diagnostic accuracy of swelling at physical examination for ultrasound‐detected synovial proliferation in haemophilia. Methods PubMed and EMBASE were searched up to 2 August 2022. Studies reporting original data on occurrence of swelling at physical examination and synovial proliferation on ultrasound of index joints in persons with haemophilia were included. Risk of bias and applicability were assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS‐2) tool. Diagnostic accuracy parameters of swelling at physical examination for ultrasound‐detected synovial proliferation were determined. Summary sensitivity and specificity were calculated using a bivariate random‐effects model. Results Fifteen studies reporting on swelling at physical examination and synovial proliferation on ultrasound in 2890 joints of 627 patients were included. Prevalence of subclinical synovial proliferation ranged between 0% and 55%. Sensitivity of swelling was low [summary estimate .34; 95% confidence interval (CI) .24‐.46], while specificity was high (summary estimate .97; CI .92‐.99). Predictive values varied widely due to inter‐study differences in prevalence of synovial proliferation. Conclusion Joint swelling has low sensitivity for presence of ultrasound‐detected synovial proliferation in haemophilia, suggesting underestimation of synovial proliferation by physical examination alone. Consequently, ultrasound screening may generate important information on synovial changes which would otherwise remain undetected.