The Hemophilia Joint Health Score version 2.1 Validation in Adult Patients Study: A multicenter international study.

Background: The Hemophilia Joint Health Score (HJHS) was developed and validated to detect arthropathy in children. Additional evidence is required to show validity in adults. We studied the convergent and discriminant construct validity of the HJHS version 2.1(HJHSv2.1) in adults with hemophilia. A secondary aim was to define age-related normative adult HJHSv2.1 reference values. Methods: We studied 192 adults with hemophilia, and 120 healthy adults in four age-matched groups-18 to 29, 30 to 40, 41 to 50, and >50 years-at nine centers. Trained physiotherapists scored the HJHS and World Federation of Hemophilia (WFH) joint score. Health history, the Functional Independence Scale of Hemophilia (FISH), Hemophilia Activities List (HAL), and Short-Form McGill Pain Questionnaire (SF-MPQ) were also collected. Results: The median age was 35.0 years. Of participants with hemophilia, 68% had severe, 14% moderate, and 18% mild disease. The HJHS correlated strongly with WFH score (Spearman's rho [rs ] = .95, P < .001). Moderate correlations were seen between the FISH (rs  = .50, P < .001) and SF-MPQ Present Pain Intensity (rs  = .50, P < .001), while a modest correlation was found with the HAL (rs  = -.37, P < .001). The HJHS significantly differentiated between age groups (Kruskal-Wallis T = 35.02, P < .001) and disease severity in participants with hemophilia. The HJHS had high internal reliability (Cronbach's α = .88). We identified duration of swelling as a redundant item in the HJHS. Conclusions: The HJHS shows evidence of strong convergent and discriminant construct validity to detect arthropathy in adults with hemophilia and is well suited for use in this population.

Effect of ABO blood group on haemostatic parameters in severe haemophilia A patients performing acute moderate-intensity exercise.

: The primary objective was to assess the effect of ABO blood group on von Willebrand factor (VWF) rise induced by four bouts of moderate-intensity physical activity, on pharmacokinetics of a B-domain-deleted recombinant FVIII (BDD-rFVIII), and haemostatic parameters in severe haemophilia A patients with a null mutation. The secondary objective was to compare the response to exercise according to infused product type in a subgroup of patients who previously participated to the same exercise protocol, while treated with a full length recombinant FVIII (FL-rFVIII). Twenty patients had two visits (rest and exercise). Blood samples were drawn before administration of BDD-rFVIII and at 6 time points, until 24 h postinfusion. FVIII activity increased transiently by 1.1-fold, but only after the first exercise session, as compared to rest. VWF:Ag and platelet count were significantly elevated after each session. Mean FVIII half-life and thromboelastography measurements were unchanged with exercise. However, 14 participants had a slight variation of FVIII half-life with exercise compared to rest (from -3.42 h to +2.51 h). Seven patients demonstrated a longer FVIII half-life (four with O blood group), whereas the remainders had a reduced half-life (three with O blood group). FVIII half-life correlated with baseline VWF:Ag at rest (r = 0.70, P < 0.001) and with exercise (r = 0.67, P < 0.002). Recovery was different between FL-rFVIII and BDD-rFVIII at rest (P = 0.032), but no significant differences were observed between half-life of products at rest and with exercise. ABO blood group and the type of rFVIII administered did not influence the response to exercise.

Adherence to treatment regimen and bleeding rates in a prospective cohort of youth and young adults on low-dose daily prophylaxis for severe hemophilia A.

BACKGROUND: When availability and/or affordability of anti-hemophilic factor concentrates are limited, optimal prophylaxis regimens in severe hemophilia A (HA) remain to be determined. In selected situations, low-dose daily prophylaxis (LDDP) may be an effective and economical option. The goal of our study was to evaluate if subjects on a LDDP regimen could achieve adherence and good clinical outcome. METHODS: Seventeen subjects (age between 15.2 and 28.4) on LDDP suffering from severe/moderate HA were followed prospectively for 2 to 3 years as part of a health-related quality of life (HRQoL) study. Bleeding and treatments data were collected using electronic diaries and validated every three months. The SF-36 questionnaire was administered at the beginning of the study and then every 6 months until the end of the study. RESULTS: The subjects (mean age 22.0, median 21.9, standard deviation 4.06), were all from a single centre and on LDDP for at least 12 months as part of their routine care before entering the study. Fifteen subjects were prescribed a daily dose of 500 IU factor VIII (FVIII) and 2 subjects received 1000 IU FVIII per day, resulting into a median dose of 7.1 IU/kg/day (ranging from 4 to 13 IU/kg/day) and of 2591 IU/kg/year. Median adherence (the percentage of the prescribed daily dose received) was 84 % (mean 80 %, range 57 % to 94 %) throughout the study. Seventy-six bleeds in the 6 index joints and 51 other types of bleeds were observed throughout the study. The median annualized bleeding rate in joints (ABRjoints) was 0.7 and the median annualized bleeding rate for all bleeds (ABRall) was 1.6. The Physical Component and Mental Component Summary scores of SF-36, and the Hemophilia Joint Health Score were not significantly different over the course of the study (respective medians of 49.8, 52.4 and 16.0 at entry; vs. 52.5, 51.5 and 16.0 upon exit). CONCLUSIONS: This prospective longitudinal study in youth and young adults shows that LDDP may be associated with low ABRs, adequate adherence and HRQoL comparable to previously reported.

Validation of a new pediatric joint scoring system from the International Hemophilia Prophylaxis Study Group: validity of the hemophilia joint health score.

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.