Objective
Repeated hemarthrosis in hemophilia causes arthropathy with pain and dysfunction. The Hemophilia Joint Health Score (HJHS) was developed to be more sensitive for detecting arthropathy than ...the World Federation of Hemophilia (WFH) physical examination scale, especially for children and those using factor prophylaxis. The HJHS has been shown to be highly reliable. We compared its validity and sensitivity to the WFH scale.
Methods
We studied 226 boys with mild, moderate, and severe hemophilia at 5 centers. The HJHS was scored by trained physiotherapists. Study physicians at each site blindly determined individual and total joint scores using a series of visual analog scales.
Results
The mean age was 10.8 years. Sixty‐eight percent were severe (93% of whom were treated with prophylaxis), 15% were moderate (24% treated with prophylaxis), and 17% were mild (3% treated with prophylaxis). The HJHS correlated moderately with the physician total joint score (rs = 0.42, P < 0.0001) and with overall arthropathy impact (rs = 0.42, P < 0.0001). The HJHS was 97% more efficient than the WFH at differentiating severe from mild and moderate hemophilia. The HJHS was 74% more efficient than the WFH at differentiating subjects treated with prophylaxis from those treated on demand. We identified items on the HJHS that may be redundant or rarely endorsed and could be removed from future versions.
Conclusion
Both the HJHS and WFH showed evidence of strong construct validity. The HJHS is somewhat more sensitive for mild arthropathy; its use should be considered for studies of children receiving prophylaxis.
For patients with hemophilia A and high-titer inhibitors treated with bypassing agents there are no reliable methods to assess treatment effect. We investigated the utility of global hemostatic ...methods in assessing treatment with bypassing agents (rFVIIa or activated prothrombin complex aPCC). All patients with hemophilia A and inhibitors followed at the Coagulation Unit or the Pediatric Coagulation Unit at Karolinska University Hospital aged 6 years and above were eligible for this noninterventional study. Baseline plasma samples were spiked with bypassing agents in increasing concentrations (aPCC 50 U/kg, 100 U/kg, 150 U/kg, and rFVIIa 90 μg/kg and 270 μg/kg) in vitro. For patients treated with factor concentrates or bypassing agents follow-up samples were collected (in vivo tests). The samples were analyzed using overall hemostatic potential (OHP), and calibrated automated thrombogram, Calibrated Automated Thrombogram (CAT). Nine patients with hemophilia A with inhibitors were included. Spiking with rFVIIa normalized the coagulation potential in 6/8 samples, in 3 only with high dose. Only one sample did not improve adequately after spiking with aPCC. The improvement in hemostasis was reliably shown by both CAT and OHP. The baseline potential was, however, more often measurable by OHP compared to CAT. Factor concentrate had been administered to 5 patients normalizing the hemostatic potential in vivo in 2 (without spiking). The hemostatic improvement induced by spiking with rFVIIa or aPCC is shown by OHP and CAT, but the results have to be evaluated in larger cohorts.
Prophylactic treatment in severe hemophilia is very effective but is limited by cost issues. The implementation of 2 different prophylactic regimens in The Netherlands and Sweden since the 1970s may ...be considered a natural experiment. We compared the costs and outcomes of Dutch intermediate- and Swedish high-dose prophylactic regimens for patients with severe hemophilia (factor VIII/IX < 1 IU/dL) born between 1970 and 1994, using prospective standardized outcome assessment and retrospective collection of cost data. Seventy-eight Dutch and 50 Swedish patients, median age 24 years (range, 14-37 years), were included. Intermediate-dose prophylaxis used less factor concentrate (median: Netherlands, 2100 IU/kg per year interquartile range (IQR), 1400-2900 IU/kg per year vs Sweden, 4000 IU/kg per year IQR, 3000-4900 IU/kg per year); (P < .01). Clinical outcome was slightly inferior for the intermediate-dose regimen (P < .01) for 5-year bleeding (median, 1.3 IQR, 0.8-2.7 vs 0 IQR, 0.0-2.0 joint bleeds/y) and joint health (Haemophilia Joint Health Score >10 of 144 points in 46% vs 11% of participants), although social participation and quality of life were similar. Annual total costs were 66% higher for high-dose prophylaxis (mean, 180 95% confidence interval, 163 - 196 × US$1000 for Dutch vs 298 95% confidence interval, 271-325) × US$1000 for Swedish patients; (P < .01). At group level, the incremental benefits of high-dose prophylaxis appear limited. At the patient level, prophylaxis should be tailored individually, and many patients may do well receiving lower doses of concentrate without compromising safety.
•Compared with intermediate-dose prophylaxis (3 × 1000 IU/wk), high-dose prophylaxis (3 × 2000 IU/wk) resulted in a 66% higher total cost.•At age 24 years, high-dose prophylaxis resulted in a small reduction in bleeding and hemophilic arthropathy, but equal quality of life.
Introduction
Von Willebrand disease (VWD) is the most widespread congenital bleeding disorder. Caregivers are highly involved in its treatment, and from the time of the child's bleeding diagnosis, ...they face new demands such as recognition of bleeds and treatment options.
Aim
The aim of this study was to assess Health related quality of life (HRQoL) in caregivers of children with moderate and severe VWD in Sweden, and to describe the impact of psychosocial aspects on the burden.
Methods
A multicentre, cross‐sectional study. The Short Form 36 Health Survey (SF‐36) was used to assess HRQoL. Caregiver burden was measured using The HEMOphilia associated Caregiver Burden scale (HEMOCAB). Children´s clinical data were collected from the Swedish national registry for bleeding disorders.
Results
Seventy caregivers of children with moderate or severe VWD were included. Caregivers of children with moderate VWD scored significantly lower in the mental health domains on SF‐36, compared to matched normative data. Psychosocial aspects that significantly impacted the caregiver burden negatively measured by HEMOCAB total score were: if the caregiver reported that VWD affected their life in general (p = .001), if the child was absent from preschool/school ≥2 day/12 months due to VWD (p = .002) or that VWD had a financial impact on the family (p = .001).
Conclusion
This study contributes to knowledge about caregivers’ HRQoL and highlights the situation of caregivers of children with moderate VWD. Furthermore, the caregiver burden was negatively affected by psychosocial aspects. Clinical follow‐ups should include assessment of psychosocial aspects to identify caregivers that are at risk of high burden.
Haemophilia is often characterized by acute haemarthrosis and synovitis arising from spontaneous bleeding episodes, particularly in the muscles and joints of the elbows, knees and ankles. Current ...treatment for patients with severe haemophilia involves coagulation factor concentrate (CFC) replacement therapy given on demand at the time of bleeding or through long‐term prophylaxis aimed at preventing future bleeds and joint disease. Although prophylaxis has many advantages over on‐demand therapy (particularly if started before age 2 and prior to any signs of joint disease), its practice varies widely even among developed countries because of several barriers. Such barriers include CFC costs and availability; patient perceptions, lifestyles and bleeding patterns; difficulties and complications arising from the use of intravenous access devices (IVADs); the development of inhibitors; and the lack of randomized clinical trials. These barriers can be overcome by tailoring treatment regimens according to individual patient bleeding patterns and CFC pharmacokinetic profiles, using IVADs selectively and judiciously, helping patients maintain normal weight and physical exercise and providing the families of patients with continuous support from healthcare providers.
The objective of this study was to examine the association of the intensity of treatment, ranging from high-dose intensive factor VIII (FVIII) treatment to prophylactic treatment, with the inhibitor ...incidence among previously untreated patients with severe hemophilia A. This cohort study aimed to include consecutive patients with a FVIII activity < 0.01 IU/mL, born between 2000 and 2010, and observed during their first 75 FVIII exposure days. Intensive FVIII treatment of hemorrhages or surgery at the start of treatment was associated with an increased inhibitor risk (adjusted hazard ratio aHR, 2.0; 95% confidence interval CI, 1.3-3.0). High-dose FVIII treatment was associated with a higher inhibitor risk than low-dose FVIII treatment (aHR, 2.3; 95% CI, 1.0-4.8). Prophylaxis was only associated with a decreased overall inhibitor incidence after 20 exposure days of FVIII. The association with prophylaxis was more pronounced in patients with low-risk F8 genotypes than in patients with high-risk F8 genotypes (aHR, 0.61, 95% CI, 0.19-2.0 and aHR, 0.85, 95% CI, 0.51-1.4, respectively). In conclusion, our findings suggest that in previously untreated patients with severe hemophilia A, high-dosed intensive FVIII treatment increases inhibitor risk and prophylactic FVIII treatment decreases inhibitor risk, especially in patients with low-risk F8 mutations.
•High-dose intensive factor VIII treatment increases the risk for inhibitor development in patients with severe hemophilia A.•In patients with severe hemophilia A, factor VIII prophylaxis decreases inhibitor risk, especially in patients with low-risk F8 mutations.
Adolescence is characterized by simultaneous physical, psychological, social and sexual changes that compound the challenges faced by parents, health care providers and adolescent haemophilia ...patients themselves. Compliance with prophylactic factor replacement therapy frequently declines when patients pass from childhood to adolescence. Familiarity with long‐term joint damage is lacking among the current generation of children who have grown up with prophylactic treatment and the tendency of teenagers to focus primarily on short‐term goals increases the likelihood that regular prophylactic replacement therapy receives low priority. Most adolescents continue prophylactic treatment prior to physical or social activities because short‐term goals are more likely to be perceived as relevant. The most important factor that influences compliance is support from parents, peers and caregivers, who provide encouragement and support active participation in health care management. During adolescence, personalized treatment strategies that suit the patient and his lifestyle are essential to ensure optimal outcomes. Physical activity is important for all adolescents and can contribute to better coordination, endurance, flexibility and strength. Physical training also contributes to healthier joints and reduces the risk of bleeding episodes in teenagers with haemophilia; however, the selection of an appropriate sport that minimizes the risk of injury and matches the patient’s skill and needs is important. Children with haemophilia may have disease‐related functional deficits and often exhibit subclinical findings in the joints; therefore an orthopaedic examination, fitness check and motion analysis may assist in guiding preventive physiotherapy and the choice of sport.
Introduction
Sweden has been a pioneer in the prophylactic treatment of haemophilia. Magnetic resonance imaging (MRI) can detect small changes in joints and can therefore give an indication of a risk ...of developing arthropathy.
Aim
To use MRI to evaluate the outcome of the Swedish ‘high‐dose regimen’ and correlate the findings to age, bleeds, joint score and physical activity.
Methods
The study group comprised 48 Swedish male patients, mean age 25 years (range 12–33 years), with severe or moderate haemophilia A or B. Data on the Haemophilia Joint Health Score (HJHS) were available and physical activity was evaluated by a self‐reported questionnaire.
Results
MRI score was recorded in 188 joints. Twenty out of 48 patients had a score of ≥1 (range 1–13) in 31 joints of which 3/31 scores were in the knees and 28/31 in the ankles. No correlation was found between the number of recorded bleeds and the MRI score or between HJHS and MRI score. There was no correlation between the physical activity and the number of joint bleeds per se, but a trend (OR 3.0) that those most physically active (19/48; 39.6%), more frequently had an MRI score of ≥1 with an overweight for the right ankle.
Conclusion
The Swedish prophylactic model offers protection against haemophilia joint arthropathy but will still not prevent osteochondral changes in some patients at young age. MRI of the ankles can signal risk of future arthropathy and indicate need to modify the prophylactic regimen.
Neutralizing antibodies (inhibitors) toward factor VIII form a severe complication in nonsevere hemophilia A, profoundly aggravating the bleeding pattern. Identification of high-risk patients is ...hampered by lack of data that take exposure days to therapeutic factor VIII concentrates into account. In the INSIGHT study, we analyzed the association between F8 mutation and inhibitor development in patients with nonsevere hemophilia A (factor VIII 2-40 IU/dL). This analysis included 1112 nonsevere hemophilia A patients from 14 centers in Europe and Australia that had genotyped at least 70% of their patients. Inhibitor risk was calculated as Kaplan-Meier incidence with cumulative number of exposure days as the time variable. During 44 800 exposure days (median, 24 exposure days per patient; interquartile range IQR, 7-90), 59 of the 1112 patients developed an inhibitor; cumulative incidence of 5.3% (95% confidence interval CI, 4.0-6.6) after a median of 28 exposure days (IQR, 12-71). The inhibitor risk at 50 exposure days was 6.7% (95% CI, 4.5-8.9) and at 100 exposure days the risk further increased to 13.3% (95% CI, 9.6-17.0). Among a total of 214 different F8 missense mutations 19 were associated with inhibitor development. These results emphasize the importance of F8 genotyping in nonsevere hemophilia A.
•The inhibitor incidence in nonsevere hemophilia A patients with certain F8 mutations approaches the inhibitor incidence in severe patients.•These findings are highly relevant for clinical practice, as they facilitate identification of high-risk patients based on F8 genotype.
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