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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., (© 2018 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Long-term outcome after joint bleeds in von Willebrand disease (VWD) (von Willebrand factor activity ≤ 30 IU/dL) could differ from moderate or severe haemophilia A (HA) (factor VIII [FVIII] 1-5 IU/dL or FVIII < 1 IU/dL). We performed a post hoc analysis on Haemophilia Joint Health Score (HJHS, 0-124), X-ray Pettersson scores (PS, 0-13/joint) and the Haemophilia Activities List (HAL, 0-100), using multivariable regression to adjust for age (rate ratio [RR] or odds ratio [OR] [95% confidence interval]). We included 48 VWD (median age, 47 years, type 3 VWD, n  = 19), 39 moderate HA (median, 39 years) and 59 severe HA patients (median, 25 years) with documented joint bleeds. VWD patients suffered repeated bleeding (lifetime > 5/joint) less often than moderate and severe HA patients (52% vs. 77% vs. 98%). HJHS and PS in VWD were similar to moderate HA (median HJHS 5 vs. 6, RR 0.9 [0.5-1.4] and PS > 3 of ≥ 1 joint OR 0.3 [0.1-1.4]), but better than in severe HA patients (median HJHS 5 vs. 9, RR 1.8 [1.1-2.9]; PS > 3 in any joint OR 0.1 [0.0-0.3]). Self-reported limitations in activities were comparable across VWD, moderate HA (HAL score < 95: 67% vs. 49%; OR 1.4 [0.5-3.6]) and young adults with severe HA (67% vs. 48%; OR 1.7 [0.7-4.4]). Despite fewer joint bleeds, joint outcome after joint bleeds was similar in VWD and moderate HA patients. Type 3 VWD patients had worst joint outcome, comparable to younger intensively treated severe HA patients. Limitations in activities occurred as often in VWD as in both moderate and severe HA., Competing Interests: K.P.M. van Galen received research support from CSL Behring and Bayer for performing the Willebrand arthropathy study. P. de Kleijn has received unrestricted research/educational support from NovoNordisk. F.W.G. Leebeek received research support from CSL Behring for performing the WiN-study, has received unrestricted research grants from Shire for studies outside the submitted work, received a travel fee from Roche and is a consultant for uniQure, NovoNordisk and Shire. J. Eikenboom received research support from CSL Behring and he has been a teacher on educational activities of Roche. E.P. Mauser-Bunschoten received unrestricted research/educational support from CSL Behring, Bayer, Baxter, LFB, Griffols, Novo Nordisk, Pfizer, Biovitrum and Sanquin. K. Fijnvandraat is a member of the European Haemophilia Treatment and Standardization Board sponsored by Shire, has received unrestricted research grants from CSL Behring and Novo Nordisk and has given lectures at educational symposiums organized by Pfizer, Novo Nordisk, Bayer and Baxter. K. Meijer received research support from Bayer, Sanquin and Pfizer, and consulting fees from Uniqure. B. Laros-van Gorkom has received unrestricted educational grants from Baxter and CSL Behring. R. Schutgens has received unrestricted research support from CSL Behring, Shire, Bayer, Novonordisk and Sanquin. K. Fischer received speaker's fees from Bayer, Baxter, CSL Behring, Biotest, Pfizer, NovoNordisk and Octapharma; performed consultancy for Bayer, Baxter, Biogen, CSL Behring, Freeline, NovoNordisk and Pfizer; and received research support from Bayer, Wyeth/Pfizer, Baxter and Novo Nordisk.None of the other authors has a conflict of interest to declare., (Georg Thieme Verlag KG Stuttgart · New York.)

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 )., (Copyright© 2017 Ferrata Storti Foundation.)

Assessment of clinical outcome after joint bleeding is essential to identify joint damage and optimise treatment, to prevent disability. However, disease-specific tools to assess the musculoskeletal status in patients with von Willebrand disease (VWD) are lacking. We aimed to determine validity and reliability of the Haemophilia Joint Health Score (HJHS) and Haemophilia Activities List (HAL) in patients with Von Willebrand disease (VWD). Ninety-six patients with VWD were included (mean age 46 years) of whom 27 had more than five documented joint bleeds. The HJHS was performed in all patients and all patients completed the HAL and Impact on Participation and Autonomy (IPA) questionnaires. Health-related quality of life (SF36) results were obtained from the prior 'Willebrand in the Netherlands' study. Joint X-rays of knees, elbows and ankles were scored according to Pettersson (PS). Internal consistency of the HJHS (Cronbach's α (α)=0.75) and HAL (α=0.89) were good. Inter-observer agreement of the HJHS was good (ICC 0.84; Limits of Agreement ± 10.3). The HJHS showed acceptable correlation with the X-ray PS (Spearman's r (r s )>0.60 all joints) and HAL (r s =0.71). The HAL also showed acceptable correlation with the SF36 physical functioning (r s =0.65) and IPA (r s =0.69). Hypothesis testing showed adequate discriminative power of both instruments: in patients with a history of >5 versus ≤ 5 joint bleeds (median HJHS 10 vs 2 (p<0.01); median HAL 77 vs 98 (p<0.01)), independent from age. In conclusion, both the HJHS and HAL are feasible to assess clinical outcome after joint bleeds in VWD.

Objectives: The radiological Pettersson score (PS) is widely applied for classification of arthropathy to evaluate costly haemophilia treatment. This study aims to assess and improve inter- and intra-observer reliability and agreement of the PS., Methods: Two series of X-rays (bilateral elbows, knees, and ankles) of 10 haemophilia patients (120 joints) with haemophilic arthropathy were scored by three observers according to the PS (maximum score 13/joint). Subsequently, (dis-)agreement in scoring was discussed until consensus. Example images were collected in an atlas. Thereafter, second series of 120 joints were scored using the atlas. One observer rescored the second series after three months. Reliability was assessed by intraclass correlation coefficients (ICC), agreement by limits of agreement (LoA)., Results: Median Pettersson score at joint level (PSjoint) of affected joints was 6 (interquartile range 3-9). Using the consensus atlas, inter-observer reliability of the PSjoint improved significantly from 0.94 (95 % confidence interval (CI) 0.91-0.96) to 0.97 (CI 0.96-0.98). LoA improved from ±1.7 to ±1.1 for the PSjoint. Therefore, true differences in arthropathy were differences in the PSjoint of >2 points. Intra-observer reliability of the PSjoint was 0.98 (CI 0.97-0.98), intra-observer LoA were ±0.9 points., Conclusions: Reliability and agreement of the PS improved by using a consensus atlas., Key Points: • Reliability of the Pettersson score significantly improved using the consensus atlas. • The presented consensus atlas improved the agreement among observers. • The consensus atlas could be recommended to obtain a reproducible Pettersson score.