W. Foppen

Discontinuing early prophylaxis in severe haemophilia leads to deterioration of joint status despite low bleeding rates

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.

Value of routine ultrasound in detecting early joint changes in children with haemophilia using the 'Haemophilia Early Arthropathy Detection with UltraSound' protocol.

Patients with haemophilia tend to bleed in large joints even during prophylactic replacement therapy. Detection of early blood‐induced joint changes may improve monitoring of treatment. The aim of this study was to explore the value of routine ultrasound in detecting early joint abnormalities in children with haemophilia on prophylaxis.

Haemophilia Joint Health Score in healthy adults playing sports.

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.

Is joint effusion on MRI specific for haemophilia

Magnetic resonance imaging (MRI) scores for haemophilic arthropathy are useful for evaluation of early and moderate arthropathy. The most recent additive International Prophylaxis Study Group (IPSG) MRI scale for haemophilic arthropathy includes joint effusion. However, it is unknown whether joint effusion is haemophilia specific. Correct interpretation of joint effusion is needed for outcome assessment of prophylactic therapies in haemophilia care. The aim of this study was to compare joint effusion on MRI between young adults with haemophilia and healthy controls. MRIs of both knees and ankles of 26 haemophilic patients (104 joints) and 30 healthy active men (120 joints) were assessed. Scans in both groups were performed in 2009/2010 and 2012 respectively. Joint effusion was measured and scored according to the MRI atlas referred by the IPSG MRI scale for haemophilic arthropathy. Median age of haemophilic patients and healthy controls was 21 and 24 years respectively. In haemophilic patients 23% of knees and 22% of ankles showed joint effusion. Healthy controls had significantly more positive scores for knee effusion (67%, P < 0.01) and a comparable scores for effusion in the ankle (17%). Joint effusion according to criteria of the IPSG MRI scale was observed significantly more often in knees of healthy controls, while findings in ankles were similar. These data suggest that joint effusion in knees and ankles is not haemophilia specific. Inclusion of joint effusion in the MRI scale is expected to reduce its specificity for haemophilic arthropathy.

Haemophilic magnetic resonance imaging score in healthy controls playing sports.

Magnetic resonance imaging (MRI) is the most sensitive imaging modality to assess joint lesions, but the clinical relevance of subtle joint changes in haemophilic patients playing sports is unknown. A haemophilia specific MRI score is available, but was never evaluated in physically active healthy controls. It is not known if unexpected MRI changes in young active haemophilic patients are due to sports participation. The aim of this study was to evaluate knees and ankles in a cohort of young active healthy men using a haemophilia specific MRI score to provide context for joint evaluation by MRI in young haemophilic patients. Three Tesla MRI of knees and ankles were performed in 30 healthy men aged 18–26 years, regularly active in sports. MR images were scored by a single independent radiologist, using the International Prophylaxis Study Group additive MRI score. One physiotherapist assessed clinical function using the Haemophilia joint health scores (HJHS). History of complaints or injuries affecting knees and/or ankles, very intensive sports and current sports activities were documented. Median age was 24.3 years (range 19.0–26.4) and median number of sports activities per week was 3 (range 1–4). Six joints (five knees, one ankle) had a history of a sports‐related injury. The median HJHS per joint was 0 out of 20 (range 0–1). All joints had a MRI score of 0. These results suggest that regular sports participation or very low HJHS scores are not associated with haemophilia specific MRI changes in knees and ankles.

Comparing findings of routine Haemophilia Joint Health Score and Haemophlia Early Arthropathy Detection with UltraSound assessments in adults with haemophilia

M. A. TIMMER,* W. FOPPEN,† R. E. G. SCHUTGENS,* M. F. PISTERS‡§ and K. FISCHER* *Van Creveldkliniek; †Department of Radiology; ‡Physical Therapy Research, Department of Rehabilitation, Physical Therapy Science and Sport, Brain Center Rudolf Magnus University Medical Center Utrecht; and §Center for Physical Therapy Research and Innovation in Primary Care, Leidsche Rijn Julius Health Care Centers, Utrecht, The Netherlands

Long-term impact of joint bleeds in von Willebrand disease: a nested case-control study

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).

Long-term effects of joint bleeding before starting prophylaxis in severe haemophilia

Early initiation of prophylaxis in severe haemophilia is critical for effective prevention of arthropathy. However, the optimum time for starting prophylaxis has not been established yet.

Diagnostic accuracy of point-of-care ultrasound for evaluation of early blood-induced joint changes: Comparison with MRI

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.

Imaging of haemophilic arthropathy: Awareness of pitfalls and need for standardization

Persons with haemophilia have a high tendency to bleed due to low levels of coagulation factor VIII or IX. Especially, the large joints are common sites of spontaneous or traumarelated bleeding.1 The synovial tissue clears intraarticular blood with accumulation of hemosiderin in the synovium resulting in inflammation of the synovial tissue. In addition, intraarticular blood has a direct effect on the cartilage by chondrocyte apoptosis. These processes may affect each other and repeated joint bleeding eventually result in chronic arthropathy through metabolic and mechanical joint changes.2 Fortunately, bleeding and arthropathy can be prevented to a large extent by regular replacement therapy with clotting factor concentrates (prophylaxis).3 However, prophylactic treatment is associated with a high clotting factors consumption and subsequent high costs (180,000 US