[show abstract][hide abstract] ABSTRACT: Joint physical examination is an important outcome in haemophilia; however its relationship with functional ability is not well established in children with intensive replacement therapy. Boys aged 4-16 years were recruited from two European and three North American treatment centres. Joint physical structure and function was measured with the Haemophilia Joint Health Score (HJHS) while functional ability was measured with the revised Childhood Health Assessment Questionnaire (CHAQ₃₈. Two haemophilia-specific domains were created by selecting items of the CHAQ₃₈ that cover haemophilia-specific problems. Associations between CHAQ, HJHS, cumulative number of haemarthroses and age were assessed. A total of 226 subjects - mean 10.8 years old (SD 3.8) - participated; the majority (68%) had severe haemophilia. Most severe patients (91%) were on prophylactic treatment. Lifetime number of haemarthroses [median=5; interquartile range (IQR)=1-12] and total HJHS (median = 5; IQR=1-12) correlated strongly (ρ = 0.51). Total HJHS did not correlate with age and only weakly (ρ=-0.19) with functional ability scores (median=0; IQR=-0.06-0). Overall, haemarthroses were reported most frequently in the ankles. Detailed analysis of ankle joint health scores revealed moderate associations (ρ=0.3-0.5) of strength, gait and atrophy with lower extremity tasks (e.g. stair climbing). In this population, HJHS summating six joints did not perform as well as individual joint scores, however, certain elements of ankle impairment, specifically muscle strength, atrophy and gait associated significantly with functional loss in lower extremity activities. Mild abnormalities in ankle assessment by HJHS may lead to functional loss. Therefore, ankle joints may warrant special attention in the follow up of these children.
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
[show abstract][hide abstract] ABSTRACT: Effective ways to prevent arthropathy in severe hemophilia are unknown.
We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor VIII (prophylaxis) or to an enhanced episodic infusion schedule of at least three doses totaling a minimum of 80 IU of factor VIII per kilogram of body weight at the time of a joint hemorrhage. The primary outcome was the incidence of bone or cartilage damage as detected in index joints (ankles, knees, and elbows) by radiography or magnetic resonance imaging (MRI).
Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P=0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups.
Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597 [ClinicalTrials.gov].).
New England Journal of Medicine 08/2007; 357(6):535-44. · 51.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: Measurement of joint health is critically important when assessing children with haemophilia. Few measures exist; they lack sensitivity to small changes, don't account for normal development and were never formally validated. To address these concerns, the Hemophilia Joint Health Score (HJHS) was developed by modifying existing scores.
To test the inter-observer and test-retest reliability of the HJHS.
Using a fully factorial design, four physiotherapists (from Canada, the United States and Sweden) examined eight boys with severe haemophilia A on two consecutive days using the HJHS. The boys ranged in age from 4-12 years and presented with variable joint damage. Six index joints (elbows, knees and ankles) were assessed on 11 impairment items including swelling, flexion and extension loss and gait. Concordance was measured by the intra-class correlation co-efficient.
Reliability of the HJHS was excellent with an inter-observer co-efficient of 0.83 and a test-retest of 0.89.
This study is the first in a series to assess the psychometric properties of the HJHS, a promising new measure of joint health in boys with haemophilia.
[show abstract][hide abstract] ABSTRACT: Assessment of impairment and function is essential in order to monitor joint status and evaluate therapeutic interventions in patients with haemophilia. The improvements in the treatment of haemophilia have required the development of more sensitive tools to detect the more minor dysfunctions that may now be apparent. This paper outlines some of the recent developments in this field. The Haemophilia Joint Health Score (HJHS) provides a systematic and robust measure of joint impairment. The MRI Scoring System has been designed to provide a comprehensive scoring system combining both progressive and additive scales. The Functional Independence Score for Haemophilia (FISH) has been developed to assess performance of functional activities and can be used in conjunction with the Haemophilia Activities List (HAL) which provides a self report measure of function. It is recommended that both measures are evaluated as these tools measure different constructs. Further refinement and testing of the psychometric properties of all of these tools is in progress. More widespread use of these tools will enable the sharing of data across the world so promoting best practice and ultimately enhancing patient care.
[show abstract][hide abstract] ABSTRACT: Routine infusions of factor VIII to prevent bleeding, known as prophylaxis, and other intensive therapies are being more broadly applied to patients with haemophilia. These therapies differ widely in replacement product usage, cost, frequency of venous access and parental effort. In order to address residual issues relating to recommendations, implementation, and evaluations of prophylaxis therapy in persons with haemophila, a multinational working group was formed and called the International Prophylaxis Study Group (IPSG). The group was comprised of haemophilia treaters actively involved in studies of prophylaxis from North America and Europe. Two expert committees, the Physical Therapy (PT) Working Group and the Magnetic Resonance Imaging (MRI) Working Group were organized to critically assess existing tools for assessment of joint outcome. These two committees independently concluded that the WFH Physical Examination Scale (WFH PE Scale) and the WFH X-ray Scale (WFH XR Scale) were inadequately sensitive to detect early changes in joints. New scales were developed based on suggested modifications of the existing scales and called the Haemophilia Joint Health Score (HJHS) and the International MRI Scales. The new scales were piloted. Concordance was measured by the intra-class correlation coefficient of variation. Reliability of the HJHS was excellent with an inter-observer co-efficient of 0.83 and a test-retest value of 0.89. The MRI study was conducted using both Denver and European scoring approaches; inter-reader reliability using the two approaches was 0.88 and 0.87; test-retest reliability was 0.92 and 0.93. These new PT and MRI scales promise to improve outcome assessment in children on early preventive treatment regimens.
[show abstract][hide abstract] ABSTRACT: This study was performed to prospectively evaluate the safety, efficacy, and cost of injecting P-colloid into joints of children with hemophilia and synovitis to decrease the rate of joint bleeding.
Eligibility included a diagnosis of hemophilia, history of more than six hemorrhages into a joint within a 6-month period, and evidence of synovitis by objective imaging. With written, informed consent, 0.25 to 1.0 mCi of P-colloid was injected into the problem joints. Safety was monitored by external beta-scanning and physical assessment. Efficacy was determined by analysis of the change in joint hemorrhage frequency from 6 months before and up to 96 months after the injection using a signed-rank test. Physical assessment and pain assessment were analyzed similarly using values obtained within 1 week before and 6 months after the radiosynoviorthesis. Cost was modeled using charges from the authors' institution in relation to existing alternative therapies.
One hundred injections were given into 91 joints in 59 children. Seven children had high-titer neutralizing antibodies to factor VIII or IX. Nine children were infected with HIV. Joints injected included 44 ankles, 19 knees, 27 elbows, and 1 shoulder. Nine joints required reinjection. All children showed a significant decrease in bleeding rate (P < 0.0001) and pain (P = 0.03), with improved physical function (P = 0.02). In one child acute lymphocytic leukemia developed, but it was judged unrelated to the two P injections that he had received 3 and 10 months before the leukemia diagnosis. There were no cases of bleeding, infection, or inflammation caused by the injection. Cost was substantially less than medical and surgical alternatives.
Radiosynoviorthesis is effective in limiting the frequency of joint hemorrhage, decreasing pain and improving function in children with hemophilia. However, long-term safety studies are needed.
Journal of Pediatric Hematology/Oncology 10/2002; 24(7):534-9. · 0.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: With the heightened interest in protocols to prevent or treat complications of haemophilia related to recurrent haemarthroses, there is a need for sensitive joint-evaluation tools. The World Federation of Haemophilia (WFH) Physical Joint Examination instrument, which was developed for persons with haemophilia worldwide, is not sensitive enough to detect early structural or functional abnormalities. Therefore, we have expanded the WFH instrument to detect more subtle abnormalities of joint structure and function, and in addition, developed a new scale specifically tailored to the dynamic growth and gait development of children. We compared the original and three new instruments in 43 children with haemophilia. The three new scales all showed better correlation with the WFH pain instrument than did the original WFH physical examination instrument (P < 0.01 for each of the new instruments vs. P > 0.05 for the WFH instrument). In addition, results of the new child physical examination instrument best conformed to a normal distribution (P=0.35) and this instrument had better overall statistical performance. This instrument should be studied further in prospective, longitudinal clinical trials of young children.
[show abstract][hide abstract] ABSTRACT: In this study, 13 children with severe hemophilia were given routine replacement infusions of factor VIII or IX to treat arthropathy. The children who had a mean age of 6.9 years (range 2.0-12.5) at initiation of prophylaxis had experienced an average of 43 acute hemorrhages (range 8-127) in the year prior to prophylaxis, of which a mean of 24 (range 5-46) were into joints. Therapy was begun in five children, using factor VIII concentrate at 20 U/kg three times a week, and one boy received factor IX concentrate 40 U/kg twice a week. This dose schedule was inadequate for three factor VIII-deficient boys and for the one factor IX-deficient boy. Two of three factor VIII-deficient boys responded to an increase to 30 U/kg prior to the 3-day interval. The dose frequency was increased to three times a week for the factor IX-deficient boy, but he continued to bleed and was taken to synovectomy. One of the original five factor VIII-deficient boys plus seven other factor VIII-deficient boys were begun on factor VIII 20 U/kg every other day; 3 boys ceased bleeding. Trough factor VIII levels were measured 24 hr after an infusion in the five boys who continued to bleed. Factor VIII dosage was adjusted to achieve a trough level of > 1%; 4 responded to an increase in the dose of factor VIII; 1 had an adequate trough but, due to compliance issues, was taken to synovectomy. Serial clinical and radiographic assessments determined stabilization of joint disease in more than one-half of the boys. No child showed reversal of abnormal radiographic findings. Institution of aggressive factor VIII and IX concentrate in children with established hemophilic arthropathy does not reverse joint disease but may alter the clinical course of hemophilia. Future studies to compare this intervention with primary prophylaxis instituted prior to the onset of recurrent joint hemorrhage are warranted.
American Journal of Hematology 10/1994; 47(2):113-7. · 4.00 Impact Factor