MRI scores of ankle joints in children with haemophilia – comparison with clinical data

Fifty-six ankle joints in 38 haemophilic boys were investigated by magnetic resonance imaging (MRI) and the findings were classified according to both the Denver- and the European scoring schemes. The different MRI scores were compared with each other and with clinical data on number of joint bleeds and the orthopaedic joint score. MRI changes that were more advanced than a small effusion were found in 33 (59%) of the ankles and osteochondral changes were observed in 20 (36%). The total number of bleeds in individual ankles ranged from 0 to 80 (mean: 11). The orthopaedic joint score was 0 for 49 ankles and ranged from one to four for seven ankles. There was a significant and strong correlation between the assessment results obtained with the two MRI scoring methods (correlation coefficients ranged from 0.80 to 0.95, P < 0.001), and both types of MRI scores were weakly but significantly correlated with the clinical data on the number of joint bleeds and the orthopaedic joint score (correlation coefficients: 0.32-0.39, P < 0.01 or P < 0.05). MRI is useful for evaluating early joint changes in patients with haemophilia. The European scoring method differentiates the arthropathic changes further than the Denver scale does, but the two different scoring methods have similar correlation to the number of joint bleeds and the orthopaedic joint score.     

Magnetic resonance imaging in teenagers and young adults with limited haemophilic arthropathy: baseline results from a prospective study

Summary. The clinical relevance of subtle changes on magnetic resonance imaging (MRI) for evaluating haemophilia treatment is unknown. To determine the relationship of findings on MRI with joint function and bleeding in joints with apparently very mild arthropathy, a prospective study was performed. Knees and ankles of 26 patients, 13–26 years, were scanned. Two blinded radiologists scored the MRI (IPSG consensus score) and the radiography [Pettersson score (PS)]. Clinical function (HJHS) was scored by one physiotherapist. Life‐time number of bleeds was collected from patient files. Of 104 joints scanned, three were excluded because of previous arthrodesis or trauma. Remaining 101 MRI scores correlated weakly with clinical function (r = 0.27, P = 0.01) and less with lifetime number of bleeds (r = 0.16, P = 0.14). MRI scores were 0 in 58 joints, including 27 with major bleeds. In three joints of patients playing intensive sports MRI showed minor changes (MRI score = 1) in the absence of bleeds. Agreement was reasonable between PS and MRI score (r = 0.41, P < 0.01). In 30% of joints, MRI detected abnormalities in soft‐tissue and cartilage, while PS was 0 points. No evidence of occult haemorrhages was found. Instead, we found no abnormalities on MRI in 43 joints with a history of repeated joint bleeding. Haemosiderin seemed associated with the time between assessment and last bleed; joints that had suffered a bleed long before MRI had hardly haemosiderin, while those with a recent bleed showed haemosiderin, suggesting joint damage may be reversible. Abnormalities detected by MRI, but not by PS were minor and their clinical implications are not yet clear.     

Controlled,cross‐sectional MRI evaluation of joint status in severe haemophilia A patients treated with prophylaxis vs. on demand

In patients with haemophilia A, factor VIII (FVIII) prophylaxis reduces bleeding frequency and joint damage compared with on‐demand therapy. To assess the effect of prophylaxis initiation age, magnetic resonance imaging (MRI) was used to evaluate bone and cartilage damage in patients with severe haemophilia A. In this cross‐sectional, multinational investigation, patients aged 12–35 years were assigned to 1 of 5 groups: primary prophylaxis started at age <2 years (group 1); secondary prophylaxis started at age 2 to <6 years (group 2), 6 to <12 years (group 3), or 12?18 years (group 4); or on‐demand treatment (group 5). Joint status at ankles and knees was assessed using Compatible Additive MRI scoring (maximum and mean ankle; maximum and mean of all 4 joints) and Gilbert scores in the per‐protocol population (n = 118). All prophylaxis groups had better MRI joint scores than the on‐demand group. MRI scores generally increased with current patient age and later start of prophylaxis. Ankles were the most affected joints. In group 1 patients currently aged 27?35 years, the median of maximum ankle scores was 0.0; corresponding values in groups 4 and 5 were 17.0 and 18.0, respectively [medians of mean index joint scores: 0.0 (group 1), 8.1 (group 2) and 13.8 (group 4)]. Gilbert scores revealed outcomes less pronounced than MRI scores. MRI scores identified pathologic joint status with high sensitivity. Prophylaxis groups had lower annualized joint bleeds and MRI scores vs. the on‐demand group. Primary prophylaxis demonstrated protective effects against joint deterioration compared with secondary prophylaxis.     

Monitoring recovery of joints after bleeding: Physical examination and ultrasound are complementary

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.     

Prophylaxis with FEIBA in paediatric patients with haemophilia A and inhibitors

The benefits shown with factor VIII (FVIII) prophylaxis relating to joint health and quality of life (QoL) provide the rationale for FEIBA prophylaxis in haemophilia A patients with persistent FVIII inhibitors. FEIBA has previously shown efficacy in preventing bleeds in inhibitor patients who failed to respond to, or were ineligible for immune tolerance induction (ITI). The study examined the outcome of paediatric patients undergoing long‐term FEIBA prophylaxis. A retrospective chart review included severe haemophilia A patients with persistent inhibitors aged ≤13 years at the start of FEIBA prophylaxis. Baseline characteristics captured dose, frequency of prophylaxis, history of inhibitor development, including baseline titre, historical peak titre and history of ITI. Outcome measurements included annual bleed rate before and during FEIBA prophylaxis, joint status and school days missed. Sixteen cases of FEIBA prophylaxis from two centres are presented. The mean age of subjects at prophylaxis initiation was 7.5 ± 3.6 years and median baseline inhibitor titre was 23 (range 3.1–170) BU. Prior to prophylaxis initiation, median annual joint bleeds among all patients was 4 (0–48), which dropped significantly after the first year of prophylaxis, to a median annual joint bleed rate of 1 (0–7; P = 0.0179). Subsequent years (median = 9) of prophylaxis therapy demonstrated similarly low annual joint bleed rates. There were no life‐threatening bleeds, no viral seroconversions or thrombotic events during FEIBA prophylaxis treatment. FEIBA prophylaxis was effective for preventing joint bleeds and subsequent joint damage, delaying arthropathy and improving outcomes in children with haemophilia A and inhibitors to FVIII, who failed or were ineligible for ITI.     

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.     

Long-term outcome of individualized prophylactic treatment of children with severe haemophilia

The development of arthropathy is a serious complication of severe haemophilia. With the use of prophylaxis, bleeds can be prevented and arthropathy delayed. We investigated whether an individually tailored prophylactic regimen can prevent arthropathy and whether it had a similar effect on orthopaedic outcome compared with that of a high-dose regimen. Efficacy was determined clinically and by radiographs of six major joints. Prophylaxis was started in 70 patients at a mean age of 4.1 years. Mean follow-up was 15.6 years (range 8-24.5 years). The mean factor VIII consumption was 2319 IU/kg/year. The mean number of joint bleeds was 3.5/year and the mean clinical score (maximum score 90) was 1.0, with a mean Pettersson joint score (maximum score 78) of 3.0 at a mean age of 13.5 years. In conclusion, long-term, early-onset, individualized prophylaxis in haemophilia is feasible and prevents arthropathy.     

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. MRI's 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.     

Can long‐term prophylaxis for severe haemophilia be stopped in adulthood? Results from Denmark and the Netherlands

Prophylaxis is the treatment of choice for children with severe haemophilia. As prophylaxis is especially important during the period of growth, the need for continued prophylaxis in adulthood should be considered. The aim of this study was to describe the incidence and outcome of stopping prophylaxis in patients with severe haemophilia who were offered prophylaxis during childhood. All patients with severe haemophilia (factor VIII/IX <0.01 IU/ml), born 1970-80, treated in two Danish and one Dutch treatment centre were studied. Data on discontinuation of prophylaxis, treatment, joint bleed frequency, clinical scores and radiological scores were collected. Eighty patients were studied. Median follow-up was 19 years (range 7-29). A total of 35% of patients discontinued prophylaxis at a median age of 21.5 years [interquartile range (IQR) 18.4-24.4], experiencing only three joint bleeds per year (IQR 1.4-8.7). Median clinical scores were similar in patients who discontinued prophylaxis [4 points (IQR 0-6)] and those who continued [3 points (IQR 1-6)], as were median Pettersson scores at 13 (IQR 1-24) vs. 13 points (IQR 5-23) respectively. In conclusion one-third of young adults with severe haemophilia on a prophylactic regimen discontinued prophylaxis in early adulthood, while maintaining a low joint bleed frequency and similar arthropathy after 4 years.     

A comparison of traditional vs. Canadian tailored prophylaxis dosing of prophylactic factor infusions in children with haemophilia A and B in a single hemophilia treatment center

Prophylactic infusion of clotting factor concentrates is a developing standard of care for individuals with haemophilia. The ideal schedule and techniques of prophylactic infusions remain incompletely defined. Our aim was to determine the optimal techniques and schedules for factor prophylaxis in paediatric patients. A retrospective electronic medical record review of all children treated with prophylactic factor infusions in a single Haemophilia Treatment Center was conducted. Comparison of traditional vs. Canadian dosing regimens and primary vs. secondary prophylaxis was made. Failure of prophylaxis was defined as the first serious bleed. A total of 58 children were identified for review. Five cases were excluded (four due to high titre inhibitors and one due to repeated non-compliance), thus there were 53 total cases: 46 with severe haemophilia, 2 with moderate haemophilia, 5 with mild haemophilia, 44 with haemophilia A and 9 with haemophilia B; 32 Traditional dosing and 21 Canadian dosing regimens. Patients on primary prophylaxis had a decreased failure rate (25%) compared to children treated with secondary prophylaxis (67%) regardless of technique of prophylaxis. When compared to a 'Traditional' factor prophylaxis schedule, the 'Canadian' tailored prophylaxis protocol was comparable with the exception of a decreased use of implanted venous devices in the 'Canadian' group. Ongoing bleeding (primarily joint bleeds) occurs with all prophylactic regimens. The lowest incidence of treatment failure was noted in children who began primary prophylaxis at a young age and before initial joint bleeds. Primary prophylaxis is superior to secondary prophylaxis regardless of dosing regimen. Traditional and Canadian dosing regimens were equivalent in outcome when measured over several years of follow-up.     

Correlation between musculoskeletal function and radiological joint scores in haemophilia A adolescents

Summary. The functional independence score in haemophilia (FISH) is a performance‐based instrument used to assess musculoskeletal function in patients with haemophilia. We aimed to evaluate the functional independence of haemophilia A adolescents and its correlation to radiological joint scores. A cross‐sectional study was carried out on 50 adolescent haemophilia A patients. Musculoskeletal function was assessed using the FISH and individual joints were assessed radiologically using the Pettersson score and MRI scale. The mean age of our patients was 16 ± 1.1 with a mean FISH of 23.32 ± 4.69 (range 13–28) and a mean Pettersson score of 2.32 ± 3.09 (range 0–13) for the knees, 1.86 ± 2.67 (range 0–11) for ankles and 1.42 ± 2.17 (range 0–10) for elbows. The mean MRI score for the knees was 3.92 ± 2.74 (range 0–10) while that for ankles was 3.16 ± 2.64 (range 0–10) and for elbows was 2.34 ± 2.63 (range 0–10). There was highly significant correlation between both radiological joint scores and FISH and between degree of factor VIII deficiency and each of FISH, Pettersson score and MRI score. MRI was superior to conventional radiography in detection of subchondral cyst formation and erosions at joint margins. Given the highly significant correlation with both radiological joint scores, FISH appears to be a reliable tool for assessment of functional independence in adolescents with haemophilia A. MRI is more sensitive than conventional radiography in detection of early joint abnormalities.     

When should prophylactic treatment in patients with haemophilia A and B start?— The German experience

Summary. Radiological and orthopaedic outcome in severe and moderate haemophilia A and B patients undergoing long-term prophylactic treatment were prospectively investigated focusing on the age of onset of prophylaxis and the number of joint bleedings prior to treatment. We report on 21 patients with severe and moderate haemophilia A and B receiving prophylactic treatment of between 3.1 and 16.1 year's duration. Three patient groups were evaluated according to the age at onset of prophylaxis. In group I prophylactic treatment was initiated in the first 2 years of life. Patients in group II received prophylaxis at the age of 3–6 years. Late-onset or secondary prophylactic treatment was started at the age of 6 years and above in seven patients (group III). All patients received virus-inactivated F VIII or F IX concentrates at dosages of 30–50 IU/kg body weight i.v. three times per week for those with haemophilia A and twice per week for those with haemophilia B. Elbow, knee and ankle joints were investigated at 3–4-yearly intervals according to the radiological and orthopaedic scores recommended by the World Federation of Haemophilia. The total number of joint bleedings before and after start of prophylaxis were recorded in all patients. In group I 7/8 patients had unaffected joints with constant radiological and orthopaedic scores of zero or 1, after a median of 11.25 years of prophylactic treatment. One patient in this group demonstrated mild radiological alterations (score 4). Patients in group II showed neither radiological nor orthopaedic alterations at study entry. Surprisingly, worsening joint scores could be detected despite ongoing prophylaxis after the 3-year interval (median orthopaedic score 4, median radiological score 8). Treatment group III already showed considerable joint damage at study entry with a median radiological score of 11 (0–33) and a median orthopaedic score of 4 (0–11). Despite prophylactic treatment, both radiological (median 19.5, range 2–47) and orthopaedic scores (median 8, range 2–12) deteriorated after 3 years. Prior to onset of prophylaxis, no or only one joint bleeding occurred in treatment group I. In group II, a median of six joint bleeds (range 1–8) was reported before prophylaxis was started. Patients in group III usually experienced a median of more than 10 joint haemorrhages (range 6–10 or more). Under prophylactic treatment the number of joint bleedings decreased significantly in group II and III. However, radiological and orthopaedic scores increased as a sign of progressing osteoarthropathic alterations in patients reporting more than five joint haemorrhages before onset of prophylaxis whereas no joint alterations could be assessed in patients with no or only one joint bleeding episode prior to prophylaxis. Even a small number of joint bleedings seems to cause irreversible osteoarthropathic alterations leading to haemophilic arthropathy. Once apparent, further progression of joint damage could not be arrested despite of prophylactic treatment (groups II and III). In order to prevent haemophilic arthropathy, effective prophylaxis should be started before or at least after the first joint bleeding in severe haemophilia A and B.     

Comparison of ultrasound and magnetic resonance imaging for diagnosis and follow‐up of joint lesions in patients with haemophilia

Haematomas and recurrent haemarthroses are a common problem in haemophilia patients from early age. Early diagnosis is critical in preventing haemophilic arthritis, and recent years have seen excellent advances in musculoskeletal ultrasound as a diagnostic tool in soft tissue lesions. In this study, we compared the results of ultrasound imaging for the diagnosis of musculoskeletal injuries in haemophilia patients with scores obtained using magnetic resonance (MRI) scans. A total of 61 haemophilia patients aged 4–82 years were included in this study. Both knees and ankles of each patient were assessed using the Gilbert (clinical assessment) and Pettersson scores (X‐ray assessment). Patients with severe haemophilia (n = 30) were examined using ultrasound and MRI (Denver scoring system). Results obtained with ultrasound and MRI in severe patients were correlated using the Pearson test. In patients with severe haemophilia, normal joints were similarly assessed with MRI and ultrasound (κ = 1.000). By component of joint assessment, haemarthrosis was similarly diagnosed with both techniques in all joints (κ = 1.000). A good positive correlation was found between these techniques in detecting and locating synovial hyperplasia (κ = 0.839–1.000, knees and ankles respectively), and erosion of margins (κ = 0.850–1.000). The presence of bone cysts or cartilage loss was better detected with MRI (κ = 0.643–0.552 for knees and ankles, and κ = 0.643–0.462 respectively). Ultrasound is useful in detecting joint bleeds, synovial hyperplasia and joint erosions, with results comparable to those of MRI. A quick and affordable technique, ultrasound imaging may be useful for monitoring joint bleeds and structure normalization and maintenance in routine practice.     

The overall effectiveness of prophylaxis in severe haemophilia

The aim of this retrospective review was to assess the overall effectiveness of prophylaxis when compared with on-demand treatment of haemophilic patients. Twenty-five children (22 with severe haemophilia A and three with severe haemophilia B) were evaluated. Five haemophilia A patients received primary prophylaxis (instituted before the onset of any joint bleed) while the other 17 haemophilia A and all three haemophilia B patients were on secondary prophylaxis. We compared factor usage, number of bleeding episodes, emergency room (ER) visits and hospitalizations while on prophylaxis to those while on demand therapy. All subjects were male, the median age at time of review was 11.4 years and at start of prophylaxis was 4.5 years. Thirteen of the 25 patients (52%) required indwelling venous catheters for access, seven of these had one or more (one-six) episodes of line sepsis. Haemophilia A patients received an average of 23.8 U kg(-1) (20-30 U kg(-1)) of recombinant factor VIII three times a week while haemophilia B patients received 50 U kg(-1) recombinant FIX twice weekly. There was a significant reduction in the mean number of major bleeds on prophylaxis from 15.5 to 1.9 per year and a significant decrease in target joints, ER visits and hospitalizations. Although factor usage per year was higher on prophylaxis, there was an overall reduction in number of bleeds and resultant decrease in hospitalizations and ER visits. By preventing new target joints, prophylaxis can lead to reduction in long-term morbidity and a better quality of life despite increased central lines and higher factor usage.     

Discontinuation of prophylactic therapy in severe haemophilia: incidence and effects on outcome

A cohort study was performed to assess adherence to early prophylactic therapy and its effects on outcome in 49 patients with severe haemophilia born 1970-1980. Median age at start of prophylaxis was 5.5 years. The majority (69%) of patients interrupted prophylactic treatment one or more times of their own accord (median total interruption 2.2 years). Patients who discontinued prophylaxis at any point tended to have more arthropathy as measured by the Pettersson scale (median 8 points versus 4 points). One-third of these patients interrupted prophylaxis for longer periods and had permanently stopped taking prophylaxis at a mean age of 20.1 years (mean +/- SD duration 4.1 +/- 4 years) and consequently experienced 5.4 +/- 3.4) joint bleeds per year. This subgroup could be identified by a predictive score based on age at start of prophylaxis, weekly dose of prophylaxis, and joint bleed frequency on prophylaxis. In conclusion, while on prophylaxis, more than two-thirds of patients with severe haemophilia try to discontinue treatment, resulting in slightly more arthropathy. One-third of these patients permanently discontinue prophylaxis in adulthood, while maintaining a low number of joint bleeds.     

Clinical outcomes and resource utilization associated with haemophilia care in Europe

We conducted a multicentre, cross- sectional study of 1042 haemophilia subjects across Europe to compare various health outcomes associated with on-demand vs. prophylactic factor-substitution therapy. Demographic, medical history, and healthcare resource utilization data were analysed along with the number of bleeding events over the past 6 months. Treatment-cost data were also examined to provide preliminary information for future economic studies. A logistic regression analysis, controlling for other statistically significant covariates, showed that patients treated on demand were 3.4 times more likely to have had a joint bleed over the previous 6 months than those treated with prophylaxis. Multiple regression analyses further confirmed these findings, because on-demand subjects had, on average, 5.15 more joint bleeds over the reporting period than patients treated with prophylaxis. Notably, these findings were even more dramatic for younger haemophilia patients when our study sample was stratified by age. Due to the high cost of factor replacement, healthcare costs were significantly higher for subjects treated prophylactically. While hospital costs for prophylaxis subjects were, on average, lower, statistically significant cost savings for prophylactic subjects were not noted. These results suggest that clinicians and health policy decision-makers should consider the advantages of prophylactic therapy for haemophilia patients in formulating treatment protocols and allocating health resources.     

The impairment in daily life of obese haemophiliacs

Summary. Obesity is a major health concern not only in the general population but also in patients with haemophilia. Little is known about the consequences of obesity for haemophilia patients. As obesity is an important risk factor for osteoarthritis, these effects may be even more pronounced in haemophilia patients who are prone to joint damage. The association between obesity and limitations in daily activities as well as the frequency of bleeds and use of factor VIII (FVIII) concentrate in obese and normal weight haemophilia patients was assessed. Fifteen obese (BMI ≥ 30 kg m^?2) and fifteen normal weight (BMI ≤ 25 kg m^?2) haemophilia A patients matched for severity and age were analysed. The Hemophilia Activities List (HAL) was used to assess the impairment in daily activities. Compared with the normal weight haemophilia patients, obese haemophiliacs had a significantly lower sum score (88/100 and 98/100, respectively, P = 0.02), which was mainly caused by an impaired lower limb function. All other components of the HAL also showed lower scores in the obese patients, but did not reach statistical significance. A higher frequency of bleeds requiring treatment with FVIII concentrate occurred in the obese haemophiliacs (17 bleeds in eight individuals) compared with the controls (three bleeds in three individuals) (P = 0.045). Compared with non‐obese haemophilia patients, obese haemophiliacs had more joint bleeds and a lower overall HAL score, which was driven by a lower limb function score. Prevention of overweight and weight reduction requires special attention from physicians treating haemophilia patients.     

Clinical outcome of moderate haemophilia compared with severe and mild haemophilia

Summary.  Information on outcome and treatment of patients with moderate haemophilia is scarce. In this study, we compared self-reported burden of disease in moderate haemophilia to severe and mild haemophilia. A nationwide questionnaire on bleeding pattern, treatment, impairment and quality of life was sent to 1567 Dutch patients with haemophilia. Out of 1066 respondents (response rate: 68%), 16% had moderate, 44% severe and 39% mild haemophilia. Median age was 36 years. Although overall outcome in moderate haemophilia was in between severe and mild haemophilia, moderate haemophilia patients did report a substantial burden of disease. The majority of patients with moderate haemophilia (73%) reported bleeds in the previous year; and a considerable proportion of moderate patients reported joint impairment (43%), chronic pain (15%), needed orthopaedic aids (24%) or were unemployed because of disability (27%). Within the group of moderate haemophilia patients, a large variation in bleeding pattern and outcome was observed. A quarter of patients with moderate haemophilia reported a more severe phenotype and intermittent use of prophylaxis. These patients reported frequent bleeding, with a median of eight bleeds per year, including two joint bleeds, and 68% reported joint impairment. In conclusion: Although outcome in moderate haemophilia is generally in between severe and mild haemophilia, moderate haemophilia patients reported a substantial burden of disease, and for more than 25% of patients with moderate haemophilia long term prophylaxis was implemented because of frequent bleeds.     

A survey of factor prophylaxis in boys with haemophilia followed in North American haemophilia treatment centres

Summary.  A survey was conducted in 2002 to determine the pattern of factor prophylaxis use in boys ≤18 years of age with haemophilia followed in North American treatment centres. Responses were obtained from 4553 cases (74% haemophilia A, 26% haemophilia B). The frequency of prophylaxis, defined as factor infusion greater than or equal to once per week for ≥45 weeks per year, was significantly higher for haemophilia A vs. haemophilia B cases (51% vs. 32%, P < 0.0001), and for boys with severe haemophilia A living in Canada vs. the USA (77% vs. 47%, P < 0.0001). Use of full-dose prophylaxis, defined as the infusion of 25–40 IU kg⁻¹ of factor VIII on alternate days (minimum three times per week) or 25–40 IU kg⁻¹ of factor IX twice weekly, was similar for boys ≤5 years of age in both Canada and the USA (30% and 33% haemophilia A and 35% and 13% haemophilia B). Reasons for initiating prophylaxis included a history of joint bleeding (88%) and age ≤2 years (23%). For prophylaxis triggered by joint bleeding, 38% of haemophilia treatment centres indicated that they would initiate prophylaxis after the first joint bleed and 66% after a history of target joint bleeding, defined most frequently as 2–4 bleeds over a 3–6 consecutive month period. A central venous line was used to ensure easy venous access for full-dose prophylaxis therapy in 80% of boys ≤5 years of age. These data offer a basis for projecting long-term factor concentrate needs for persons with haemophilia living in North America.     

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.