Orthopaedic Joint Score Research Articles

The Bone Microarchitecture Deficit in Patients with Hemophilia Is Influenced by Arthropathy, Hepatitis C Infection, and Physical Activity.

Low bone mineral density (BMD) is common in patients with hemophilia (PWHs). The aim of the present study was to describe BMD and microarchitecture in PWHs in Northern Germany and to determine factors contributing to possible skeletal alterations. Demographic characteristics, BMD and microarchitecture, bone metabolism markers, and orthopaedic joint score (OJS) were assessed during routine check-ups. Areal BMD was assessed by dual-energy X-ray absorptiometry (DXA) at the hip and lumbar spine. Volumetric BMD and microarchitecture were quantified by high-resolution peripheral quantitative computed tomography at the distal radius and tibia. Eighty male PWHs (median age, 33 years; range, 18-77) were retrospectively analyzed, of whom 67 (84.0%) and 13 (16.0%) had hemophilia A and B, respectively. Fifty-four (68.0%), six (7.0%), and 20 (25.0%) patients had severe, moderate, or mild hemophilia, and 35 (44.0%) were hepatitis C virus (HCV) positive. DXA analysis revealed low BMD (Z-score ≤ - 2.0) in 27.5% of PWHs, and higher bone turnover values were associated with lower BMD. Bone microarchitecture was dominated by cortical deficits at the radius and trabecular deficits at the tibia. Cortical deficits at the radius were influenced by lower body mass index, low-grade inflammation, and treatment regimen (higher cortical thickness on primary prophylaxis). Trabecular alterations at the tibia were mainly associated with OJS and HCV status. A positive effect of self-reported sportive activity on BMD could be shown. In conclusion, our findings demonstrate that the site-specific microarchitectural deficit observed in PWHs is primarily negatively influenced by poor joint status, inflammation, HCV infection, and high bone turnover.

LPS-induced expression and release of monocyte tissue factor in patients with haemophilia

In haemophilia, thrombin generation and fibrin deposition upon vascular injury critically depend on the tissue factor (TF)-driven coagulation pathway. TF expression by monocytes/macrophages and circulating microvesicles contributes to haemostasis, thrombosis and inflammation. Inflammation is a hallmark of blood-induced joint disease. The aim of this study is to correlate TF production by whole-blood monocytes with inflammatory markers and clinical parameters in patients with moderate-to-severe haemophilia A or B (n = 43) in comparison to healthy males (n = 23). Monocyte TF antigen and microvesicle-associated TF procoagulant activity (MV TF PCA) were measured immediately after blood draw (baseline) and following incubation of whole blood with buffer or lipopolysaccharide (LPS) using two-colour flow cytometry and chromogenic FXa generation assay, respectively. Patients with HIV or uncontrolled HBV/HCV infections were excluded. TF was hardly detectable and not different in baseline and buffer-treaded samples from both groups. Stimulation with LPS, however, induced monocyte TF production, with increased TF-specific mean fluorescence intensity (P = 0.08) and MV TF PCA (P < 0.05) in patients compared to controls. Patients also had elevated hs-CRP and IL-6 serum levels (P < 0.001), which correlated with LPS-induced TF parameters. Further exploratory analyses revealed that the presence of systemic (low-grade) inflammation and boosted LPS-induced monocyte TF production were mainly restricted to patients with clinically controlled HBV and/or HCV infection (n = 16), who were older and also had a significantly worse orthopaedic joint score than patients with no history of viral hepatitis (P < 0.01). Our study delineates a previously unrecognised link between systemic inflammation and inducible monocyte TF production in patients with haemophilia A or B.

Posturographic and ankle muscle activation characteristics in patients with haemophilia.

The objective of this work was to examine the interrelations of posturographic and surface EMG (SEMG) characteristics of ankle muscles in patients with haemophilia while standing naturally. Surface EMG of five bilaterally recorded ankle muscles was conducted in 24 patients with haemophilia (PwH, age: 42 [11] years, mean [SD], 22 A, 2 B, 21 severe, 3 moderate) with median (quartiles) WFH orthopaedic joint score of 30 (20/39) points and 24 non-haemophilic controls (Con, age: 42 [12]). Force plate (IBS) signals were captured simultaneously during bipedal stance with eyes open. Load proportion of the left and right sides as well as heel and forefoot were calculated via four independent pressure transducers. Overall, weight distribution (WD) indices are reported with higher results representing a poorer WD. Analyses of WD showed large differences between groups (PwH: 10.2 [5.4], Con: 5.2 [2.9], P<0.001, d=1.15). After clustering PwH, large effects (P=0.02, ηp 2 >0.16) were found for amplitude ratios of the lateral gastrocnemius (LG) muscle. In PwH, the degree of joint alteration of the right lower limb was associated with load proportion of the left side (ρ>0.64, P=0.001). Patients with greater dysbalance showed higher forefoot loads and appeared to compensate their altered joint situations with considerably higher amplitude ratios of LG. Further studies should investigate whether therapeutic interventions could alter postural alignment and muscle activation and how these can influence patients' joint function and symptoms.

The impact of sport on health status, psychological well-being and physical performance of adults with haemophilia.

There is increasing recognition that sport is important for individuals with haemophilia; however, there remains a paucity of data of the importance of this in adults, many of whom already have joint pathology related to childhood bleeds and treatment access. This multicentre, cross-sectional study presents the impact of sport on health-related quality of life (HRQoL), physical performance and clinical outcomes in adults with haemophilia. Fifty adults aged 35.12±14.7 with mild (n = 12), moderate (n = 10), or severe (n = 28) haemophilia A (70%) or B (30%) from four haemophilia centres across the United Kingdom participated in the study. A total of 64% were overweight/obese according to their BMI; median orthopaedic joint scores using the WFH Orthopaedic Joint Score (OJS) were 6 (range 0-48). On a VAS pain scale (range of 0-10), patients reported mean score of 5.66 ± 2.4. 36% of participants reported not doing any sport, mainly due to their physical condition. However, 64% of participants reported undertaking sporting activity including contact sports, mostly twice per week in average 4 h week(-1) . Participating in sport did not have a statistically significant impact on HRQoL; except in the domain 'sport and leisure' of the Haem-A-QoL. Patients doing more sport reported significantly better HRQoL than those doing less sport (P < 0.005). Those doing sport for more than 4 h week(-1) had a significantly better physical performance than patients doing less sport (assessed with Hep-Test-Q). Encouraging physical activity and sport in older patients with haemophilia may have a direct impact on their HRQoL; thus, education about sport activity should be incorporated into routine haemophilia care.

The impact of social factors on outcomes in patients with bleeding disorders.

In haemophilia, clinical outcomes are mainly determined by the severity of clotting factor deficiency, treatment regimen, availability of clotting factor concentrate and age. Information about the relevance of patient-related factors such as education, social status or impact of the disease on the patient's life is scarce. To assess the impact of social status and disease-related impairment of certain aspects of the patient's life on clinical and psychosocial outcomes in patients with inherited bleeding disorders (PWBD). Consecutive patients of a single centre were assessed by questionnaires on social status and quality of life (SF-36). Social status was defined by school and professional education, employment and financial income of patients as well as school education of their parents. Fifty-seven PWBD (mean age, 38 ± 16 years) were enrolled, 60% were treated on-demand; PWBD had a median number of 2.5 (0-34) annual bleeds and a median orthopaedic joint score of 6 (0-38). No significant differences were found for clinical and psychosocial outcomes across social status groups. More than half of the patients reported that haemophilia had an impact on their school education, childhood and leisure activities. Patients with a high impact of haemophilia on their lives were less satisfied with their lives (P < 0.002), reported worse quality of life in all domains of the SF-36, had a worse joint score (P < 0.024) and reported more pain (P < 0.013). The perceived impact of haemophilia on patients' lives seems to have a stronger impact on clinical and psychosocial outcomes than patients' actual social status.

Towards personalizing haemophilia care: using the Haemophilia Severity Score to assess 178 patients in a single institution

The phenotypic variability in haemophilia is well documented; however, the biological basis beyond factor VIII and IX activities to explain the differing clinical pictures of the disease remains unclear. It has therefore been of interest to explore other modulators of the disease's variability. Furthermore, a scoring system that reflects the multiple facets of haemophilia symptoms would be useful to compare patients via a comprehensive assessment tool. To this end, Schulman et al., created a measure known as the Haemophilia Severity Score (HSS) as one way to compare phenotypic severity. The aim of this study was to document the differing symptomatology of haemophilia patients using the HSS. Clinical data for 178 haemophilia patients without inhibitors were reviewed and annual incidence of haemarthrosis, orthopaedic joint scores and annual factor usage calculated. Each parameter was then entered into the formula to create the HSS for haemophilia A and B patients with mild, moderate and severe factor deficiencies. Variability in the HSS for patients with the same baseline level of factor was observed for all three deficiency levels and both haemophilia types. In addition, we found that moderate and severe haemophilic B patients tended to have more morbidity based on the above calculations than the haemophilic A counterparts. The HSS is a comprehensive tool that allows for easy numerical comparison of haemophilic patients and elucidates the variable clinical presentation of the disease. The HSS could be used to stratify patients via other possible modulators of haemophilia and discover other aetiologies of the disease.

Physical activity and functional abilities in adult males with haemophilia: a cross‐sectional survey from a single US haemophilia treatment centre

Physical activity and functional ability are important determinants of quality of life and these metrics are affected by both haemophilia and ageing. Outside haemophilic arthropathy, risk factors leading to reduced physical activity and function in people with haemophilia (PWH) are under-explored. The purpose of this analysis was to determine risk factors for reduced physical activity and functional limitations in PWH. A secondary analysis was conducted on data indexing physical activity and functioning of 88 PWH using data originally collected as part of a cross-sectional study at a single large haemophilia treatment centre. The Framingham Physical Activities Index (PAI), the Hemophilia Activities List (HAL) and the Timed Up-and-Go Test (TUG) were the outcome measures. The World Federation of Haemophilia (WFH) orthopaedic joint score was used as a measure of arthropathy. Multiple linear regression analysis was used to assess the relationship between the outcome measures and covariates. Worsening WFH joint score was independently associated with all three outcome measures (P < 0.05). Increasing age was associated with reduced PAI and increased TUG time (P < 0.05). The HAL summary score was decreased in patients with chronic liver disease (P = 0.006). The adjusted R(2) for each model was ≤ 0.35. This study provides evidence for the relationship between arthropathy and reduced physical functioning/activity, but also highlights that much of the variation in physical functioning/activity is not explained by haemophilia-related characteristics.

Haemophilia Care in Europe: the ESCHQoL study

The aim of this study was to determine the clinical conditions of patients with haemophilia within Europe as recommended by the European Commission. In this multicentre, cross-sectional, ambispective study, conducted within 21 European countries patients' clinical data were collected, amongst others haemophilia type, severity, treatment pattern, use of factor products, bleeding, orthopaedic joint scores and infections. A total of 1400 patients, 84.3% with haemophilia A and 15.7% with haemophilia B were enrolled by 42 centres between 2004 and 2006. Thereof, 417 were children (30.0%) and 983 were adults (70.0%). About 70% of patients had severe factor deficiency (<1%). More than half of the adults were carriers of chronic infections (12.6% HIV, 55.8% HCV), compared to only 3.8% children (no HIV, 2.9% HCV). Patients were grouped according to per capita amount of clotting factor used in patients' region of residence in 2005: region 1: >5 IU; region 2: 2-5 IU; region 3: <2 IU. Paediatric and adult patients in region 3 had median numbers of three and eight joint bleeds, respectively, with worse joint scores compared to region 1 with zero and one bleed. Prophylactic therapy was used in only 31.3% children and 8.9% adults with severe haemophilia in region 3 compared to 93.7% and 54.1%, respectively, in region 1. Statistical analysis revealed that residence in areas with low factor consumption/availability is the most prominent risk factor for joint disease. Access of European patients with haemophilia to optimal care with safe factor VIII concentrates is limited and depends on the region of residence.

Development and validation of a new questionnaire for the assessment of subjective physical performance in adult patients with haemophilia – the HEP‐Test‐Q

Specific research studies for the investigation of physical performance in haemophilic patients are rare. However, these instruments become increasingly more important to evaluate therapeutic treatments. Within the frame of the Haemophilia & Exercise Project (HEP), a new questionnaire, namely HEP-Test-Q, has been developed for the assessment of subjective physical performance in haemophilic adults. In this article, the development and validation of the HEP-Test-Q is described. The development consisted of different phases including item collection, pilot testing and field testing. The preliminary version was pilot-tested in 24 German HEP-participants. Following evaluation and preliminary psychometric analysis, the HEP-Test-Q was revised. The final version consists of 25 items pertaining to the domains 'mobility', 'strength & coordination', 'endurance' and 'body perception', which was administered to 43 German haemophilic patients (43.8 +/- 11.2 years). Psychometric analysis included reliability and validity testing. Convergent validity was tested correlating the HEP-Test-Q with SF-36, Haem-A-QoL, HAL and the Orthopaedic Joint Score. Discriminant validity tested different clinical subgroups. Patients accepted the questionnaire and found it easy to fill in. Psychometric testing revealed good values for reliability in terms of internal consistency (Cronbach's alpha = 0.96) and test-retest reliability (r = 0.90) as well as for convergent validity correlating highly with Haem-A-QoL, HAL and SF-36. Discriminant validity testing showed significant differences for age, hepatitis A and hepatitis B and the number of target joints. HEP-Test-Q is a short and well-accepted questionnaire, assessing subjective physical performance of haemophiliacs, which might be combined with objective assessments to reveal aspects, which cannot be measured objectively, such as body perception.

Early long‐term FEIBA prophylaxis in haemophilia A patients with inhibitor after failing immune tolerance induction: A prospective clinical case series

Persistent high-titre inhibitors after immune tolerance induction (ITI) increase the risks of haemorrhage and arthropathy, resulting in high morbidity and mortality. Long-term prophylaxis with bypassing agents may avert these risks. This study was performed to assess the effectiveness and safety of early prophylaxis with FEIBA in preventing bleeding and joint damage after failed ITI. Seven paediatric patients proceeded immediately after failed ITI to long-term FEIBA prophylaxis at 60-100 IU kg(-1) dosages and various dosing intervals depending upon bleeding tendency. Bleeding episodes and joint status were assessed. Thrombin generation assays (TGA) were also used to gauge treatment response. FEIBA prophylaxis was commenced at a median age of 6.0 years (range, 1.5-11.8 years) and continued for a median duration of 6.9 years (range, 0.8-17.1 years). The mean annual incidence of joint bleeding was 1.5 episodes per year with a 95% CI of 0.7-3.0 episodes per year. Muscle bleeding incidence was 0.9 episodes per year (CI, 0.6-1.2 episodes per year). No patient experienced major joint damage during prophylaxis. Median Pettersson and orthopaedic joint scores at the last follow-up evaluation were 4 (range, 0-12) and 2 (range, 0-4) respectively. Endogenous thrombin potential (ETP) measured by TGA exceeded 80% of normal after FEIBA infusion in the majority of the patients. Between regular prophylactic infusions, mean trough ETP equalled 2.6 fold of the inhibitor plasma control mean. FEIBA prophylaxis was well-tolerated without serious thrombotic or other complications. The only adverse event involved venous access. Therefore early long-term FEIBA prophylaxis is valuable in controlling bleeding and preserving joint integrity in young patients failing ITI.

Quality of life is associated to the orthopaedic status in haemophilic patients with inhibitors

Inhibitors represent one major complication of haemophilia treatment, as they increase the risk of bleeding, physical disability and mortality. The Cost Of Care Inhibitors Study (COCIS) showed that modern strategies applied to manage patients with inhibitors adsorb high amounts of resources but provide satisfactory levels of Health-Related Quality-of-Life (HR-QoL). This paper focuses on determinants of HR-QoL in inhibitory patients. Fifty adult patients, enrolled by 11 Italian Haemophilia Centres, were clinically assessed and filled in two HR-QoL generic questionnaires: the EuroQol instrument (EQ-5D) and the Short Form-36 (SF-36). According to our results, bleeding frequency and inhibitor titres were not found associated with HR-QoL. Global HR-QoL, and in particular the physical component of wellbeing in these patients was found negatively associated with their orthopaedic condition: the EQ-5D Visual Analogue Scale (P<0.001) scores, the SF-36 domain 'physical functioning' and 'physical component summary' (P<0.01) scores were found significantly correlated with the orthopaedic joint score, even after adjusting for patients' age. These results were confirmed by those from the EQ-5D profile. To conclude, the COCIS study is the first study showing that HR-QoL in inhibitory patients is impaired by their orthopedic status, while other aspects do not seem to influence patients' global wellbeing. Our results suggest that while the management of this complication is satisfactory, the attention has now to be focused on the prevention of the orthopaedic problems in these patients, which nowadays constitute one of the most important aspects to be considered in the haemophilia care.

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.

Primary prophylaxis in severe haemophilia should be started at an early age but can be individualized.

The frequency of joint bleeds and orthopaedic joint scores were evaluated in 121 patients with severe haemophilia who had started prophylactic treatment with clotting factor concentrates at least once weekly before the age of 10. 75 of the patients started before the age of 3, 31 at the age of 3-5 and 15 at the age of 6-9. Each subgroup was evaluated separately. In addition, a regimen of one infusion weekly was compared with that of two (haemophilia B) or three (haemophilia A) infusions weekly in each patient. A significant decrease in the overall number of joint bleeds per year was found after shortening the infusion interval (P<0.005), but the individual bleeding pattern varied. In survival analysis of the first pathologic joint score event, those who started prophylaxis before the age of 3 had a better outcome overall than those starting at later ages (P=0.001). However, in subgroup analysis, no significant difference was seen in the annual number of joint bleeds and the development of arthropathy between those starting with, or shifting to, the more intensive regimen before the age of 3 and those that were put on this regimen at the age of 3-5. Age at start of prophylaxis was found to be an independent predictor for the development of arthropathy (P=0.0002), whereas dose and infusion interval at start were not. Our data emphasize the importance of starting replacement therapy during the first years of life. However, it seems that when beginning the regimen it can be individualized and adjusted according to the bleeding pattern. In this way, the need for a venous access system may be assessed on an individual basis.

Can haemophilic arthropathy be prevented?

Can haemophilic arthropathy be prevented?

Haemophilia prophylaxis in young patients--a long-term follow-up.

To review long-term prophylactic factor treatment in young patients with severe haemophilia A and B, focusing on the orthopaedic and radiological outcome. We received 34 patients with severe haemophilia A (n = 29) and B (n = 5), aged 7-22 years. Age at start of treatment was 1-4.5 years. Dosages of factor concentrate (F VIII and F IX, respectively) were 25-40 IU/kg body weight, three times a week for haemophilia A and twice a week for haemophilia B. The patients had been checked annually over a 5-year period (1990-95). Orthopaedic and radiological joint scores were evaluated according to recommendations by the World Federation of Haemophilia. All results were obtained at the Department for Coagulation Disorders, University of Lund, Malmö University Hospital, Malmö, Sweden. Orthopaedic and radiological joint scores were found to have remained unchanged during follow-up in almost all patients and to be still zero (i.e. no unaffected joints) in 79% (n = 27) of the patients. There is a growing international consensus haemophilic arthropathy can be prevented by administering early high-dose prophylaxis. The results of the present investigation strongly support this opinion.

Twenty-five years' experience of prophylactic treatment in severe haemophilia A and B.

In Sweden, prophylactic treatment of boys with severe haemophilia has been practised since 1958 in an attempt to convert the disease from a severe to a milder form. The present study population consisted of 60 severe haemophiliacs (52 A, 8 B), aged 3-32 years. Treatment is started when the boys are 1-2 years of age, the regimens used being 24-40 IU F VIII kg-1 three times weekly in haemophilia-A cases (i.e. greater than 2000 IU kg-1 annually) and 25-40 IU F IX kg-1 twice weekly in haemophilia-B cases. The orthopaedic and radiological joint scores (maximum scores of 90 and 78, respectively) are evaluated as recommended by the World Federation of Haemophilia. Of those subjects aged 3-17 years, 29 out of 35 individuals had joint scores of zero. The oldest group had only minor joint defects. The VIII:C and IX:C concentrations had usually not fallen below 1% of normal. All 60 patients are able to lead normal lives. In conclusion, it appears to be possible to prevent haemophilic arthropathy by giving effective continuous prophylaxis from an early age, and preventing the VIII:C or IX:C concentration from falling below 1% of normal.