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.
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.
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.
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.
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.
The Hemophilia Joint Health Score (HJHS) is a validated outcome tool developed for the assessment of joint health in people with hemophilia. The ordinal joint score assesses 9 items in 6 index ...joints. It is recognized as an optimal measurement of arthropathy in children and young adults. The aim of this study was to develop an updated scoring system for the HJHS that may overcome the limitations of its current ordinal scoring structure.
A survey was developed using 1000Minds decision‐making software. Respondents were provided with discrete choice tasks of ranking alternatives to determine the preference weight, or relative importance, placed on different criteria for each HJHS item. The survey was distributed to an anonymous sample of health care professionals with extensive experience in the physical examination of joints in people with hemophilia.
A total of 64 musculoskeletal health care professionals participated; with a 64% survey completion rate. The HJHS item weights provide a sum to 1.0; the highest‐ranked item was extension loss (0.139) followed by swelling (0.121), whereas the lowest was duration of swelling (0.057) followed by muscle atrophy (0.08). Compared to the original, the relative efficiency of the new score was 5.4.
Observed differences in preference weights for HJHS items highlight the potential under‐ or overestimation of true joint health using the current ordinal scoring system. An updated scoring system using weighted items may improve the precision of HJHS assessment, leading to improved clinical management of joint health, while providing a robust research tool.
A lack of uniformity in the choice of outcome measurement in hemophilia care and research has led to studies with incomparable results. We identified a need to define core outcome measures for use in ...research and clinical care of persons with hemophilia.
To move toward a core set of outcome measures for the assessment of persons with hemophilia in research and practice.
A modified nominal groups process was conducted with an international group of hemophilia experts, including persons with hemophilia as follows. Step 1: item generation for all potential outcome measures. Step 2: survey where respondents voted on the relative importance and usefulness of each item. Steps 3/4: 2‐day meeting where attendees voted for items they valued, followed by open discussion and a second round of voting. Step 5: survey where respondents selected their top five items from those with >50% agreement at the meeting.
The highest ranked items for the pediatric core set (% agreement) are treatment satisfaction (92.7%), joint health (83.3%), a measure of access to treatment (82.5%), a measure of treatment adherence (72.5%), and generic performance based physical function (72.1%). The highest ranked items for the adult core set (% agreement) are total bleeding events (88.1%), EuroQol five dimensions (85.4%), treatment adherence (82.1%), joint health (79.1%), and number/location of bleeds per unit time (78.6%).
This process generated a list of preferred outcome measures to consider for assessment in persons with hemophilia. This information now requires refinement to define optimal core sets for use in different clinical/research contexts.
For persons with hemophilia, optimization of joint outcomes is an important unmet need. The aim of this initiative was to determine use of ultrasound in evaluating arthropathy in persons with ...hemophilia, and to move toward consensus among hemophilia care providers regarding the preferred ultrasound protocols for global adaptation.
A global survey of hemophilia treatment centers was conducted that focused on understanding how and why ultrasound was being used and endeavored to move toward consensus definitions of both point‐of‐care musculoskeletal ultrasound (POC‐MSKUS) and full diagnostic ultrasound, terminology to describe structures being assessed by ultrasound, and how these assessments should be interpreted. Next, an in‐person meeting of an international group of hemophilia health care professionals and patient representatives was held, with the objective of achieving consensus regarding the acquisition and interpretation of POC‐MSKUS and full diagnostic ultrasound for use in the assessment of musculoskeletal (MSK) pathologies in persons with hemophilia.
The recommendations were that clear definitions of the types of ultrasound examinations should be adopted and that a standardized ultrasound scoring/measurement system should be developed, tested, and implemented. The scoring/measurement system should be tiered to allow for a range of complexity yet maintain the ability for comparison across levels.
Ultrasound is an evolving technology increasingly used for the assessment of MSK outcomes in persons with hemophilia. As adoption increases globally for clinical care and research, it will become increasingly important to establish clear guidelines for image acquisition, interpretation, and reporting to ensure accuracy, consistency, and comparability across groups.
Patients with hemophilia may experience joint damage, which can impair participation, yet few studies have examined the impact hemophilia may have on social participation and quality of life.
The ...aims of this study are to assess the relationship between patient social participation and self‐perception, social support, and impact on the family.
A random representative sample of 50 boys with hemophilia from The Hospital for Sick Children, Toronto, Canada, completed measures of social participation (Participation Scale for kids), self‐perception (Self‐Perception Profile for children and adolescents), and social support (Social Support Scale for children). Participants' parents completed Family Impact Module of the Pediatric Quality of Life Inventory. Data were analyzed using Pearson product‐moment correlations.
Social participation was strongly correlated with self‐perception subscales Social Acceptance (r= −0.5, p= <0.001) and Global Self‐Worth (r= −0.6, p= <0.001) for all participants. The Athletic Competence subscale was strongly correlated for adolescents only (r= −0.6, p= <0.01). There were strong correlations between social participation and social support from parents (r= −0.6, p= <0.001), teachers (r= −0.5, p= <0.001), and classmates (r= −0.6, p= <0.001) and moderate correlations for support from close friends (r= −0.4, p= <0.01). There were no significant correlations with family impact.
In the context of a country with unlimited access to safe clotting factor concentrates, boys with hemophilia have few social participation restrictions. Although correlational findings do not represent causality, they suggest that encouragement of social participation may be beneficial in boys with hemophilia to increase self‐perception as well as strengthen their social support network.
In countries with restricted access to clotting factor concentrates, early implementation of low‐dose prophylaxis is recommended over episodic treatment.
The objective of this 1‐year prospective ...secondary prophylaxis study was to evaluate the efficacy of a dose/frequency escalating protocol in young boys with hemophilia A in China.
Boys were started on a low‐dose protocol (minimum 10–15 IU/kg of factor VIII FVIII twice weekly). Escalation was based on index joint bleeding, swelling/persistent joint swelling, and serial ultrasound (gray scale and color Doppler) examinations of index joints.
Thirty‐three boys, median age 4.8 years (interquartile range, 3.8‐6.1) were enrolled in a 3‐month observation period that preceded a 1‐year prophylaxis phase. A significant reduction in total bleeding events (43.0%, P= .001), index joint bleeds (53.2%, P= .002), and target index joint bleeds (70.0%, P= 0.02) was observed during the prophylaxis phase. During the prophylaxis period, 40% of target joints resolved. The percentage of boys with zero index joint bleeds increased significantly (P= .004) from 51.5% during the observation phase to 81.8% in last quarter of the prophylaxis phase (months 10‐12). There was no progression of arthropathy based on physical examination (Hemophilia Joint Health Score), X‐ray, and ultrasound obtained at entry into the prophylaxis phase and at study exit. The median FVIII consumption over the prophylaxis phase was 1786 IU/kg/y.
A low‐dose, individualized prophylaxis protocol, guided by individual bleeding profiles and serial assessment of joint status, enables escalation of treatment intensity in boys with severe hemophilia A, leading to a significant reduction in bleeding events and reduction in target joint bleeding.
Prophylaxis reduces the frequency of bleeds in boys with severe hemophilia and is the standard care for their management in resource‐abundant countries. The effect of prophylaxis on Health‐Related ...Quality of Life (HRQoL) has not been established, because the sample sizes of most studies are too small to explore the relationship of multiple factors that influence HRQoL.
The aim of this study was to assess the impact of hemophilia severity and treatment regimen on HRQoL and to establish the minimum important difference (MID) using the international level of score distributions. HRQoL data were pooled from 7 studies across 9 countries. HRQoL was measured using the Canadian Hemophilia Outcomes–Kids’ Life Assessment Tool (CHO‐KLAT). A mixed‐effect linear regression analysis was employed to assess the impact of prophylaxis on the CHO‐KLAT score.
Data from 401 boys with hemophilia were analyzed (57.6% severe hemophilia and 57.6% receiving prophylaxis). The model revealed that receiving prophylaxis was significantly associated with higher HRQoL (regression coefficient 8.5, 95% confidence interval CI 3.9‐13.1). Boys with severe hemophilia had a significantly lower HRQoL as compared to boys with moderate and mild hemophilia whose CHO‐KLAT scores were 7.0 and 6.6 points higher, respectively. There was a significant interaction between treatment and disease severity (P=0.023), indicating prophylaxis has the most significant impact in boys with severe hemophilia. Based on these pooled data, the MID of the CHO‐KLAT was established at 6.5.
This study confirms the positive effect of prophylaxis on HRQoL in boys with hemophilia in a real‐world setting and provides initial benchmarks for interpreting HRQoL scores based on use of the CHO‐KLAT instrument.
Aim
The objective of this survey was to understand the global trends of imaging assessments in persons with haemophilia, focusing on point‐of‐care ultrasound (POCUS). Insights into the barriers ...impeding its widespread proliferation as a frontline imaging modality were obtained.
Methods
The survey opened in September of 2017 and closed in May of 2018. Haemophilia Treatment Centres (HTCs) treating both paediatric/adult patients were the population of interest. A REDCap survey of 25 questions was disseminated to 232 clinical staff in 26 countries.
Results
The majority of respondents (88.3%, 91/103) reported that POCUS is most useful to confirm or rule out a presumed acute joint bleed. European HTCs reported the highest routine use of POCUS at 59.5% (22/37) followed by HTCs in the “Other” countries of the world at 46.7% (7/15) and North American HTCs at 43.9% (25/57). At the time of the survey, physiotherapists were identified as the clinical staff who perform POCUS 52.8% (28/53) of the time, in contrast with nurses/nurse practitioners who represent only 5.7% (3/53) of users. The greatest perceived barriers to the implementation of POCUS are the lack of trained healthcare professionals who can perform POCUS at 69.2% (74/107) and the overall time commitment required at 68.2% (73/107).
Conclusion
Despite POCUS being used in 49.5% (54/109) of sampled HTCs, it is still utilized almost 30% less globally than full diagnostic ultrasound. A list of barriers has been identified to inform HTCs which challenges they will likely need to overcome should they choose to incorporate this imaging modality into their practice.
Background:
In China, 90% of boys with severe hemophilia A (SHA) manifest significant arthropathy by age 6 years (Wu R et al Haemophilia, 2014). Short‐term pilot studies demonstrated that low‐dose ...prophylaxis (10‐15 IU/kg x2 /week) reduced joint bleeds by 80% but was ineffective in eliminating joint damage (Wu R et al Haemophilia, 2011, Tang L et al Haemophilia, 2013). Optimizing prophylaxis in China for boys with SHA is an urgent priority.
Aims:
To investigate the efficacy of an individualized, dose escalating prophylaxis protocol in young boys with SHA in China
Methods:
This is a prospective, ethics approved clinical trial conducted at 2 major Hemophilia Treatment centers in China. Boys with SHA (baseline FVIII < 2%), ages 1‐7 years, inhibitor negative, >50 Exposure Days and a history of index joint (elbows, knees, ankles) bleeds were eligible. The design included 4 dose escalation steps; Step 1: 10‐15 IU/kg x2/week; Step 2: 10‐15 IU/Kg, x3/week; Step 3: 15‐20 IU/Kg x3/week; and Step 4: 20‐25 IU/Kg every other day. A priori escalation criteria were based on the frequency of index joint bleeds, scores from the Hemophilia Joint Health Score (HJHS) and Ultrasound (US) examinations of index joints.
Results:
30 patients were consented and enrolled, with only 1 drop-out. The mean age was 4.8 yrs. (range: 2.1 ‐ 7.9 yrs.) and the median follow up observation period was 10 months (range: 6 ‐11 months). In total, the patients have completed 76% of the required number of months on study (275/360 patient months). Musculoskeletal (MSK) assessment showed a total of 19 boys with target joints (65%). In addition, a total of 22 patients completed 36 dose escalations. Of these patients currently on prophylaxis, 8 patients are on step 1 (28%); 9 on step 2 (31%), 10 on step 3 (34%); and 2 on step 4 (7%). The criterion for escalations are summarized in Table 2.
Conclusions:
This is the first prospective, individualized, dose escalating prophylaxis study for boys with SHA in China with the goal of minimizing bleeding and joint damage. Findings from the HJHS and US examinations to guide dose escalation, in conjunction with index joint bleeds, is a unique feature of this clinical trial. Our results indicate a promising reduction in joint bleeds by using the 4-step escalation low dose regimens with equal utilization of Steps 1, 2 and 3 by the patients. Low dose prophylaxis may be ineffective in some cases and assessments of bleeding patterns and joint structure/function is important to inform modification of prophylactic regimens. These observations will be useful in the design of cost effective prophylaxis regimens for boys with SHA in China.
This study is financially supported by a grant from Bayer HealthCare Co. Ltd., China.
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Wu:Bayer Healthcare Co. Ltd., China: Employment.
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