Home About us Contact
|
Home About us Contact | ||
|
|
||
Arthropathy
Kinds of Arthropathy Selected AbstractsRecombinant activated factor VII for haemophilia patients with inhibitors undergoing orthopaedic surgery: a review of the literatureHAEMOPHILIA, Issue 2 2008A. OBERGFELL Summary., Arthropathy is prevalent in patients with haemophilia and inhibitors and is a major source of pain and disability, significantly reducing quality of life. Recombinant activated factor VII (rFVIIa; NovoSeven®) is one of the treatments available for acute life-threatening bleeding episodes in haemophilia patients with inhibitors. It has also been used successfully in a range of orthopaedic surgical procedures in these patients. This is a review of published data on elective orthopaedic procedures in haemophilia patients with inhibitors under cover of rFVIIa from January 2002 to November 2006. Articles were retrieved from MEDLINE using specified search parameters. Twelve articles covering a total of 80 orthopaedic procedures were identified. In the vast majority of cases, rFVIIa provided safe and effective haemostatic cover during orthopaedic surgery with no bleeding complications. There was variation in the administered dose, although the majority of patients were treated with 90 ,g kg,1 bolus followed by either continuous infusion or bolus infusion. Of those cases reporting bleeding complications, most were considered to be related to an inadequate amount of rFVIIa. The cumulative experience presented here suggests that rFVIIa is safe and effective for providing adequate haemostatic cover for haemophilia patients with inhibitors undergoing orthopaedic surgery. The optimal dosing regimen and mode of administration has yet to be identified. Further controlled trials are needed to confirm these experiences. [source] Pathogenesis of haemophilic synovitis: clinical aspectsHAEMOPHILIA, Issue 2007W. K. HOOTS Summary., Arthropathy remains a major cause of morbidity in patients with haemophilia. Frequent bleeding into the joints leads to joint damage with resultant contractures, joint deformities and arthritis. This in turn leads to muscle atrophy, limited physical activity, osteoporosis and disability. Even though several studies of prophylactic factor replacement for persons with severe haemophilia demonstrate improved joint function, this therapy is still not readily available to most people with haemophilia around the world and a universal treatment protocol has not been used. In this article, we discuss key issues in the treatment of severe haemophilia: the optimal timing of initiation and termination of therapy, dosing options and goals of therapy. The options for countries where prophylaxis is not readily available are also discussed. Most studies are small and not randomized making consensus treatment recommendations difficult to formulate. Randomized, clinical trials are needed to provide the answers regarding the optimal treatment of patients with severe haemophilia. [source] Changes in treatment strategies for severe haemophilia over the last 3 decades: effects on clotting factor consumption and arthropathyHAEMOPHILIA, Issue 5 2001K. Fischer A cohort study was performed among 214 patients with severe haemophilia, born 1944,1994, to describe changes in treatment over the last 3 decades and its effects on clotting factor consumption and haemophilic arthropathy. Data on treatment strategy, clotting factor consumption, and outcome were collected for 3567 patient years (from 1972 to 1998), and 493 Pettersson scores were analysed. Median follow up was 17 years (range 6,27 years), and median age in 1998 was 27.6 years. Since 1965, replacement therapy, prophylaxis, and home treatment have been used and treatment intensified. Over the last 3 decades, annual clotting factor consumption increased by 260%, for both prophylactic and on-demand treatment. Annual clotting factor consumption kg,1 increased during childhood and appeared to stabilize in early adulthood for patients born 1965,79, who were treated with early replacement therapy or early prophylaxis. In contrast, clotting factor consumption increased continuously for patients born before 1965, who had had no access to replacement therapy during the early years of their life. The annual number of joint bleeds decreased over the years. Arthropathy as measured by the Pettersson score generally became apparent around the age of 15 years and was lowest in patients treated with primary prophylaxis. In conclusion, clotting factor consumption has increased and haemophilic arthropathy has decreased due to the intensification of treatment for severe haemophilia over the last 3 decades. Annual clotting factor consumption stabilizes in adulthood for patients who receive early intensive treatment. [source] Clinical and radiographic scores in haemophilic arthropathies: how well do these correlate to subjective pain status and daily activities?HAEMOPHILIA, Issue 6 2002T. Wallny Summary. Haemophilic patients who reached adulthood before the establishment of prophylactic treatment frequently show multiple and substantial arthropathies. The aim of this study was to determine to what extent haemophiliac's subjective impairment due to arthropathies correlates with objective clinical and radiographic parameters. By means of a questionnaire and a visual analogue scale, we consulted 79 haemophiliacs concerning their joint-pain status, how these were treated and to what extent their daily activities had been affected. Using a scoring system suggested by the Advisory Committee of the World Federation of Haemophilia, clinical evaluation was performed. Radiographs of 60 patients were assessed by means of the Petterson scale. The results were statistically compared. We found a significant correlation between pain intensity and clinical pathology as well as between pain intensity and radiographic joint damage for both knees and for the right ankle. The number of painful joints correlated well with the number of clinically/radiographically affected joints. The more pronounced the objective damage to joints, the more frequently patients claimed to have constant pain, depressive episodes and a dependency on pain-relieving medication. The more pronounced the objectively assessed damage to the knee and ankle joint, the higher the likelihood that the patient suffers from severe joint pain and reduction of activity. Treatment of painful symptoms from arthropathies is often insufficient. Scores and questionnaires may help to define the haemophiliacs pain status more clearly, thereby offering a possibility of assessment and long-term observation. [source] Quantitative determination of the diagnostic accuracy of the synovitis score and its componentsHISTOPATHOLOGY, Issue 3 2010Elisabeth Slansky Slansky E, Li J, Häupl T, Morawietz L, Krenn V & Pessler F (2010) Histopathology,57, 436,443 Quantitative determination of the diagnostic accuracy of the synovitis score and its components Aims:, To assess the diagnostic accuracy of a three-component synovitis score and to determine the relative contribution of each of its components to its overall discriminatory power. Methods and results:, The synovitis score was determined in 666 synovial specimens: normal synovium, n = 33; post-traumatic arthropathy (PtA), n = 29; osteoarthritis (OA), n = 221; psoriatic arthritis (PsA), n = 42; and rheumatoid arthritis (RA), n = 341. The discriminatory abilities of the score and its components were quantified with binary and multicategory receiver operating characteristic (ROC) analysis. The score differentiated all arthropathies accurately from normal tissue (area under the ROC curve, AUC: 0.87,0.98) and RA from OA or PtA (AUC: 0.85 for both), but could not distinguish well within pairs of inflammatory or degenerative arthropathies. AUCs of the intimal hyperplasia and stromal cellularity components correlated with the AUCs of the complete score markedly more strongly (r = 0.94 and 0.91, respectively) than the inflammatory infiltration component (r = 0.60). Multicategory ROC analysis ranked the score several-fold higher than any of its components, and the components in the order stromal cellularity>intimal hyperplasia>infiltration. Conclusion:, Combining three distinct histological parameters into a three-component score produces greatly increased overall diagnostic power. The discriminatory ability of the score stems more from measuring proliferative than infiltrative aspects of synovitis. [source] Evidence That Peroxynitrite Affects Human Osteoblast Proliferation and Differentiation,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2002Francisco Airton Castro Da Rocha Abstract Peroxynitrite (PN), a nitric oxide (NO·)-derived anion, has been associated with NO· damage in various cell types. We examined the effects of adding PN to cultured human osteoblast-like (hOB) cells obtained after hip arthroplasty. Exposure to PN (0.1-0.4 mM) decreased both hOB proliferation and differentiation, measured by [3H]thymidine uptake and alkaline phosphatase production, respectively. Incubation with 3-morpholinosydnonimine (SIN-1; 0.25-1 mM), an NO· and O2, donor that leads to PN release, also reduced both hOB proliferation and differentiation. Coincubation with both superoxide dismutase (SOD; 100 U/ml) and catalase (CAT; 50 U/ml), rendering SIN-1 a pure NO· donor, reversed its effects on hOB proliferation and differentiation. However, SIN-1-induced NO· production, measured by nitrite release to the hOB medium, was not altered by cotreatment with SOD and CAT. Expression of nitrotyrosine by hOB, a marker of PN action, was significantly increased after SIN-1 addition, as compared with untreated cells, as revealed by Western blot analysis. Interleukin-1, (IL-1,) and interferon , (IFN-,) but not tumor necrosis factor , (TNF-,) also significantly increased nitrotyrosine expression in these cells. These data show that PN is at least partially responsible for osteoblast derangement by NO· and that cytokines released during inflammatory arthropathies can induce PN production in hOB cells. [source] Avascular necrosis not Charcot'sDIABETIC MEDICINE, Issue 10 2001Y. P. Samarasinghe Abstract Background, A case of avascular necrosis (AN) of the navicular bone, in a 24-year-old woman with Type 1 diabetes with peripheral neuropathy, in the absence of any history of direct trauma is presented. The clinical and radiological features at presentation suggested an evolving Charcot arthropathy (CA), but subsequent serial X-rays clearly confirmed AN. Conclusions Swelling and foot deformity in association with long-standing diabetic peripheral neuropathy is suggestive of CA, although AN, a less common condition, may show the same clinical features. It is therefore important to undertake further confirmatory radiological investigations if there is any doubt about the diagnosis. Diabet. Med. 18, 846,848 (2001) [source] The role of prophylaxis in bleeding disordersHAEMOPHILIA, Issue 2010E. BERNTORP Summary., The rationale for long-term prophylaxis in more severe forms of von Willebrand's disease (VWD) is obvious, as mucosal bleeding and haemophilia-like joint bleeds resulting in chronic morbidity may occur. However, the experience with prophylactic treatment in this group is scanty. An international VWD Prophylaxis Network (VWD PN) was established in 2006. The VWD PN will investigate prophylaxis with retrospective and prospective studies. Eighteen centres in Europe and North America are recruiting patients and an additional 40 centres are preparing for or evaluating participation. In the absence of randomized prospective studies for most rare bleeding disorders, guidelines for prophylaxis are a subject of controversy. In situations where there is a strong family history of bleeding, long-term prophylaxis is administered in selected cases. Short intervals of prophylaxis can also be given before some surgeries or during pregnancy. The benefits of prophylaxis must be balanced by the risk of side effects. Therefore, it is essential to delineate its management in a specialized comprehensive care environment. In haemophilia, decades of clinical experience and numerous retrospective and, recently, prospective studies clearly demonstrate that prophylactic treatment is superior to on-demand treatment, regardless of whether the outcome is the number of joint- or life-threatening bleeds, arthropathy evaluated by X-ray or MRI, or quality of life measured by generic or haemophilia-specific instruments. Optimal prophylactic treatment should be started early in life (primary prophylaxis) but various options exist for the dose and dose interval. These depend on the objective of treatment in the individual patient, which, in turn, is dependent on resources in the health care system. [source] Co-morbidity in the ageing haemophilia patient: the down side of increased life expectancyHAEMOPHILIA, Issue 4 2009E. P. MAUSER-BUNSCHOTEN Summary., Because of an increased life expectancy, (age-related) co-morbidity is becoming a common occurrence in haemophilia patients. In this review, haemophilia-related and non-haemophilia-related medical problems, treatment recommendations and psychosocial consequences in ageing haemophilia patients are discussed. Haemophilic arthropathy is an important cause of pain and disability, and a frequent indication for surgery in haemophilia patients. In addition, many adult patients are infected with hepatitis C or HIV, the consequences and treatment of which can add to physical and mental discomfort. Moreover, inhibitors against factor VIII can also develop in adulthood, especially in patients with mild haemophilia. Hypertension is reported to occur more often in haemophilia patients than in the general population. Other internal problems, like renal abnormalities, overweight, diabetes mellitus and hypercholesterolemia are discussed. Haemophilia seems to protect against cardiovascular disease, although the incidence is increasing. Recommendations are given on dealing with tooth extractions, surgical interventions and sexuality problems in patients with haemophilia. In addition to haemophilia in itself, co-morbidity has a major psychological impact, and an important effect on quality of life. It can also result in complex treatment regimens, in which coordination between health care workers is essential. [source] Current approaches in haemophilic arthropathy of the hipHAEMOPHILIA, Issue 3 2009H. A. MANN Summary., The hip is considered to be one of the main load bearing joints of the body. In the haemophilic patient joint bleeds can be catastrophic, leading to long-term joint degeneration and accompanying arthritis. In this review we explore the mechanisms of joint destruction, with particular consideration of the anatomy of the hip and how it may influence disease progression. We also review current strategies for treatment including hip replacement in the haemophilic patient and describe our experiences as a unit. Finally we evaluate future prospects in the management of hip disease in haemophilia. [source] The benefits of prophylactic treatment with APCC in patients with haemophilia and high-titre inhibitors: a retrospective case seriesHAEMOPHILIA, Issue 3 2009L. A. VALENTINO Summary., Prophylactic infusion of factor concentrates is a safe, effective intervention for preventing arthropathy in patients with haemophilia; on-demand treatment is insufficient to prevent the orthopaedic complications and subsequent haemophilic arthropathy that stem from recurrent joint haemorrhages. The usefulness of prophylaxis in haemophilia patients without inhibitors suggests that patients with haemophilia and inhibitors could derive similar benefits. In patients with haemophilia and high-titre (>5 BU mL,1) inhibitors, bleeding episodes are treated with bypassing agents such as activated prothrombin complex concentrates (APCCs) and recombinant activated factor VII (rFVIIa, NovoSeven®; Novo Nordisk A/S, Bagsvaerd, Denmark). It is possible to administer bypassing therapy regularly to prevent haemorrhages, with the goal of limiting arthropathy and serious life- and limb-threatening bleeding. The data evaluating the efficacy and safety of this approach in patients with inhibitors are limited, consisting of results from one prospective trial and retrospective case reports. This report describes our experience with the prophylactic use of the APCC Factor Eight Inhibitor Bypassing Activity, Anti-Inhibitor Coagulant Complex, Vapor Heated (FEIBAÔ; Baxter AG, Vienna, Austria). Data from patients at one treatment centre were retrospectively evaluated. Case records of six patients with haemophilia A or B and high-titre inhibitors were identified. When APCC was administered regularly, most patients exhibited a reduction in the numbers of haemorrhages, an improvement in orthopaedic status, and an improvement in quality of life. Prophylaxis with APCC can reduce haemorrhages and halt further joint deterioration in patients with haemophilia and inhibitors. [source] Forum on: the role of recombinant factor VIII in children with severe haemophilia AHAEMOPHILIA, Issue 2 2009M. FRANCHINI Summary., The development of recombinant FVIII (rFVIII) products, fuelled by the need for improved safety of treatment arising from the dramatic widespread blood-borne virus transmission in the 1970,1980s revolutionized the care of children with haemophilia A over the last two decades. The larger availability of perceived safer replacement therapy associated with the introduction of rFVIII products reassured the haemophilia community and there was a strong push in some Western countries to treat haemophilic children only with rFVIII. Moreover, this significantly contributed in the 1990s to the diffusion outside Northern Europe of prophylactic regimens implemented at an early age to prevent bleeding and the resultant joint damage (i.e. primary prophylaxis), together with the possibility of home treatment. These changes led to a substantial improvement of the quality of life of haemophilic children and of their families. The general agreement that primary prophylaxis represents the first-choice treatment for haemophilic children has been recently supported by two randomized controlled trials carried out with rFVIII products, providing evidence on the efficacy of early prophylaxis over on-demand treatment in preserving joint health in haemophilic children. However, the intensity and optimal modalities of implementation of prophylaxis in children, in particular with respect to the issue of the venous access, are still debated. A number of studies also supports the role of secondary prophylaxis in children, frequently used in countries in which primary prophylaxis was introduced more recently. With viral safety now less than an issue and with the more widespread use of prophylaxis able to prevent arthropathy, the most challenging complication of replacement therapy for children with haemophilia remains the risk of inhibitor development. Despite conflicting data, there is no evidence that the type of FVIII concentrate significantly influences the complex multifactorial process leading to anti-FVIII alloantibodies, whereas other treatment-related factors are likely to increase (early intensive treatments due to surgery or severe bleeds) or reduce (prophylaxis) the risk. Although the optimal regimen is still uncertain, eradication of anti-FVIII antibodies by immune tolerance induction (ITI), usually with the same product administered at inhibitor detection, should be the first-choice treatment for all patients with recent onset inhibitors. This issue applies particularly to children, as most patients undergo ITI at an early age, when inhibitors usually appear. The availability of a stable and long-lasting venous access represents a leading problem also in this setting. These and other topics concerning rFVIII treatment of haemophilic children were discussed in a meeting held in Rome on 27 February 2008 and are summarized in this report. [source] Successful angiographic embolization of recurrent elbow and knee joint bleeds in seven patients with severe haemophiliaHAEMOPHILIA, Issue 1 2009R. KLAMROTH Summary., In haemophilic joints with high-grade arthropathy, bleeds occur that do not respond to replacement therapy of the deficient coagulation factor. The reason may be pathologically reactive angiogenesis in chronic synovitis. Seven patients with severe haemophilia A or haemophilia B experienced recurrent massive bleeds of one elbow joint or knee joint in the absence of trauma. After initial application of factor VIII or IX (fVIII/fIX; 50 IU kg,1 bodyweight), there was only slow and never complete relief of symptoms. Despite intensive secondary prophylaxis maintaining the plasma level of factor concentrate at minimum 50%, new massive bleeds at the same location occurred. Vascular bleeding was suspected. Angiography of the arteries was performed via the femoral artery. Vessels identified as potential bleeding sources were embolized with embolization fluid (ONYX) in eight joints (six elbow and two knee joints). Under low-dose prophylactic treatment (15 IU fVIII or fIX per kg bodyweight for three times per week), no recurrent severe bleed unresponsive to coagulation factor replacement occurred after a mean observation time of 16 months after embolization. The consumption of factor concentrate decreased to one-third of the amount consumed before embolization. In conclusion, angiographic embolization with a non-adhesive liquid embolic agent might be considered as a promising therapeutic and coagulation factor saving option in joint bleeds not responding to replacement of coagulation factor to normal levels. [source] Obesity: a new disaster for haemophilic patients?HAEMOPHILIA, Issue 5 2008A nationwide survey Summary., The prevalence of obesity, an important risk factor for both cardiovascular disease and arthropathy, is strongly increasing in the general population, but data for the haemophilia population are scarce. Obesity may have a more profound effect on arthropathy and on cardiovascular disease in patients with haemophilia. To assess the prevalence of obesity in haemophilia patients and install adequate measures, if necessary. We performed a nationwide postal survey to measure the prevalence of overweight and obesity in Dutch haemophilia patients in 1992 (n = 980) and 2001 (n = 1066). A random sample of the Dutch male population served as the control group. In adult haemophiliacs, the prevalence of overweight (BMI 25,30 kg m,2) increased from 27% to 35% (95% CI 31.1,38.0) and the prevalence of obesity (BMI ,30 kg m,2) doubled from 4% to 8% (95% CI 6.0,10.1), which was comparable with the general population. The increased prevalence of obesity in boys with haemophiliacs, which tripled in 10 years, is alarming. The increased prevalence of overweight and obesity in patients with haemophilia may have a profound effect on morbidity and quality of life of haemophilia patients by aggravating pre-existing arthropathy and predisposing aged patients to cardiovascular disease. Measures to prevent overweight in haemophiliacs are therefore urgently needed. [source] Cost-utility analysis of Canadian tailored prophylaxis, primary prophylaxis and on-demand therapy in young children with severe haemophilia AHAEMOPHILIA, Issue 4 2008N. RISEBROUGH Summary. Primary prophylaxis is the emerging standard treatment for boys with severe haemophilia. Tailored (escalating-dose) prophylaxis (EscDose), beginning at a low frequency and escalating with repeated bleeding may prevent arthropathy at a lower cost than standard prophylaxis (SP). From a societal perspective, we compared the incremental cost per joint-haemorrhage that is avoided and quality-adjusted-life-year (QALY) gained of SP and EscDose to on-demand (Demand) therapy in severe haemophilia A boys treated to age 6 using a decision analytic model. Costs included factor VIII (FVIII), professional visits and tests, central venous placement/complications, hospitalization, home programmes and parents' lost work-days. Resource utilization was estimated by surveying 17 Canadian clinics. The natural history of bleeding and other probabilities were determined from a longitudinal chart review (n = 24) and published literature. EscDose costs an additional $3192 per joint-haemorrhage that was avoided compared with Demand whereas SP costs an additional $9046 per joint-haemorrhage that was avoided compared with EscDose. Clinic costs and lost wages were reduced by 60,80% for EscDose and SP compared with Demand. EscDose attained more QALYs than SP and Demand on account of less bleeding than Demand and lower need for ports than SP. The incremental cost per QALY for EscDose vs. Demand was $542 938. EscDose was less expensive with similar QALYs compared to SP. Sensitivity analysis was performed on all probability- and cost-estimates, and showed the model was sensitive to the cost of FVIII and the SP and target joint utilities. In conclusion, prophylaxis will substantially improve clinical outcomes and quality of life compared to Demand treatment, but with substantial cost. [source] Inter- and intra-observer reliability of radiographic scores commonly used for the evaluation of haemophilic arthropathyHAEMOPHILIA, Issue 3 2008M. SILVA Summary., Although the severity of haemophilic arthropathy is commonly assessed using established radiographic scoring systems, there is limited available information about their inter- and intra-observer reliability. The purpose of the present study was to establish the inter-observer reliability (IEOR) and intra-observer reliability (IAOR) of three different methods available for the classification of haemophilic arthropathy, including the Arnold and Hilgartner classification, a modification to the Arnold and Hilgartner system described by Luck et al., and the classification described by Pettersson et al. Antero-posterior and lateral radiographs of 54 haemophilic joints were included for the analysis. To determine the IEOR for each one of the three radiographic systems, the radiographs were randomly evaluated by four observers, including two orthopaedic surgeons, one orthopaedic resident and one haematologist. For the determination of IAOR, all four reviewers repeated the assessment in a similar fashion, after a period of at least 2 weeks. IEOR and IAOR for the three classification systems was established using kappa (,) statistics. A Spearman rank correlation was used to determine the similarities between each reviewer's own interpretative scales. The IEOR was low for the Arnold and Hilgartner system (, = 0.35, P , 0.001) and the Luck system (, = 0.38, P , 0.001), but even lower for the Pettersson system (, = 0.06, P = 0.1). For the Pettersson system, particularly low , values were observed for the presence or absence of osteoporosis (, = 0.11, P = 0.0027), enlarged epiphysis (, = 0.10, P = 0.0039), erosion of joint margins (, = 0.11, P = 0.0018), and joint deformity (, = 0.16, P = 0.00001). However, a relatively high Spearman rank correlation for all three scales [rs = 0.75 (P < 0.001) for Arnold and Hilgartner system, rs = 0.74 (P < 0.001) for the Luck system and rs = 0.81 (P < 0.001) for Pettersson system] indicated an overall, general agreement among the reviewers with regard to the severity of the haemophilic arthropathy. There was a moderate IAOR value for both, the Arnold and Hilgartner system (, = 0.57, P = 0.00001) and the Luck system (, = 0.62, P = 0.00001) with a low IAOR value for the Pettersson system [, = 0.22, P = 0.00001). Currently available radiographic scoring systems for haemophilic arthropathy have low inter- and intra-observer reliability rates. Improvements, either through education or modification of the scoring systems, are critical in an era where correlations between clinical and radiographic scores have received significant attention. [source] The co effect of prophylaxis and radiosynovectomy on bleeding episodes in haemophilic synovitisHAEMOPHILIA, Issue 3 2008J. BRECELJ Summary., Prophylactic substitution treatment and radiosynoviorthosis have a leading role in preventing irreversible haemophilic arthropathy. The aim of the study was to evaluate the effects of prophylaxis treatment and radiosynovectomy on the length of intervals between subsequent haemorrhages in haemophilic patients. Thirty-three joints were treated with radiosynovectomy in 28 patients with bleeding disorders. 90Y colloid was used in knees and 186Re colloid for elbows, shoulders and ankles. Twenty patients were on prophylaxis. Joint X-rays were evaluated on the Pettersson scale between 0 (normal) and 13 (severe joint destruction). During an observation period (range 6,44 months) bleeding episodes were recorded and data statistically analysed. Before radiosynovectomy, increasing intensity of the prophylaxis 10% lengthens intervals between two haemorrhages by 1% (P < 0.05). In patients with a Pettersson score higher than nine, intervals between bleedings are shorter by 73% (P < 0.05), in comparison with patients with lower Pettersson scores of 0,5. After radiosynovectomy, the length of the first non-bleeding interval increased by 120% (to 60 days) in comparison with the intervals before the procedure (P < 0.001). But, in the following year and half, every subsequent non-bleeding interval was 8% shorter (P < 0.1). In that period, prophylaxis shortened the non-bleeding interval by 1.7% (P < 0.05) per 10% increase of its intensity. Radiosynovectomy is more efficient in patients with less affected joints and is less efficient in younger patients. Prophylaxis reduced time between the bleedings episodes after isotope application. Before radiosynovectomy, prophylaxis reduces the number of haemorrhages. Our findings support data previously published by Rodriguez-Merchan et al. [J Thromb Haemost, 5 (2007) P-W-126]. [source] Haemophilic knee arthropathy with extension contractureHAEMOPHILIA, Issue 3 2008R. J. HAWKINS No abstract is available for this article. [source] Total ankle replacement for end-stage arthropathy in patients with haemophiliaHAEMOPHILIA, Issue 3 2008P. RADOSSI No abstract is available for this article. [source] Reliability and construct validity of the compatible MRI scoring system for evaluation of elbows in haemophilic childrenHAEMOPHILIA, Issue 2 2008A. S. DORIA Summary., We assessed the reliability and construct validity of the Compatible MRI scale for evaluation of elbows, and compared the diagnostic performance of MRI and radiographs for assessment of these joints. Twenty-nine MR examinations of elbows from 27 boys with haemophilia A and B [age range, 5,17 years (mean, 11.5)] were independently read by four blinded radiologists on two occasions. Three centres participated in the study: (Toronto, n = 24 examinations; Atlanta, n = 3; Cuiaba, n = 2). The number of previous joint bleeds and severity of haemophilia were reference standard measures. The inter-reader reliability of MRI scores was substantial (ICC = 0.73) for the additive (A)-scale and excellent (ICC = 0.83) for the progressive (P)-scale. The intrareader reliability was excellent for both P-scores (ICC = 0.91) and A-scores (ICC = 0.93). The total P- and A-scores correlated poorly (r = 0.36) or moderately (r = 0.54), but positively, with clinical-laboratory measurements. The total MRI scores demonstrated high accuracy for discrimination of presence or absence of arthropathy [P-scale, area-under-the-curve (AUC) = 0.94 ± 0.05; A-scale, AUC = 0.89 ± 0.06], as did the soft tissue scores of both scales (P-scale, AUC = 0.90 ± 0.06; A-scale, AUC = 0.86 ± 0.06). Areas-under-the-curve used to discriminate severe disease demonstrated high accuracy for both P-MRI scores (AUC = 0.83 ± 0.09) and A-MRI scores (AUC = 0.87 ± 0.09), but non-diagnostic ability to discriminate mild disease. Similar results were noted for radiographic scales. In conclusion, both MRI scales demonstrated substantial to excellent reliability and accuracy for discrimination of presence/absence of arthropathy, and severe/non-severe disease, but poor to moderate convergent validity for total scores and non-diagnostic discriminant validity for mild/non-mild disease. Compared with radiographic scores, MRI scales did not perform better for discrimination of severity of arthropathy. [source] Pathogenesis of haemophilic synovitis: experimental studies on blood-induced joint damageHAEMOPHILIA, Issue 2007L. A. VALENTINO Summary., Hemarthrosis is a common manifestation of haemophilia, and joint arthropathy remains a frequent complication. Even though the exact mechanisms related to blood-induced joint disease have not yet been fully elucidated, it is likely that iron deposition in the synovium induces an inflammatory response that causes not only immune system activation but also stimulates angiogenesis. This process ultimately results in cartilage and bone destruction. Investigating the processes that occur in the early stages of blood-induced joint disease in humans has been very limited. Therefore, the use of haemophilic animal models is critical to augment the understanding of this phenomenon. This article discusses three cellular regulators (p53, p21 and TRAIL) induced in synovial tissue that are important for iron metabolism. A cartilage remodelling programme induced by the release of cytokines and growth factors that result in articular damage is also discussed. Full elucidation of the pathogenesis of haemophilic joint disease is required to identify new avenues for prevention and therapy. [source] An outline of the current orthopaedic management of haemophilic disease of the upper limbHAEMOPHILIA, Issue 5 2007M. Z. B. CHOUDHURY Summary., There remains a relative paucity in the literature regarding upper limb manifestations of haemophilic arthropathy. Haemophilia has a wide range of clinical manifestations, often presenting with orthopaedic complications. These arise from multiple haemarthroses which exact a cumulative toll on the fabric of the joints. Although the lower limbs are predominantly affected due to their load-bearing nature, upper limb disease is common. This arises from the mechanical demands on the upper limb as the elbow and shoulder become partially weight bearing on use of walking aids such as elbow crutches. [source] European Study on Orthopaedic Status of haemophilia patients with inhibitorsHAEMOPHILIA, Issue 5 2007M. MORFINI Summary., ,Development of inhibitors against factor VIII (FVIII) or factor IX (FIX) in haemophilia patients is one of the most serious complications of repeated exposure to replacement therapy and has major clinical and economic consequences. To evaluate the relationship between inhibitor status of haemophilia patients and their quality of life (QoL) and degree of arthropathy and to compare the orthopaedic status of patients with/without inhibitors. An observational, cross-sectional, case control study enrolling: group A (n = 38), males aged 14,35 years, with severe congenital haemophilia A or B who had inhibitors against FVIII/FIX >5 years; group B (n = 41), as group A, but aged 36,65 years and group C (n = 49), as group A, but without inhibitors. Socio-demographics: medical history, clinical characteristics and QoL were assessed. In groups A and B, 16% and 27% were hospitalized for orthopaedic procedures vs. 4% in group C. Patient mobility was also severely reduced in groups A and B, with 24% and 22% using wheelchairs vs. 4% in group C, and 50% and 51% needing a walking aid vs. 29% in group C. Significantly more joint pain was reported by patients in group A vs. those in group C; clinical/radiological orthopaedic scores were also worse in group A vs. group C. Significantly more joint abnormality was reported by patients in group A vs. group C. The burden of orthopaedic complications and the impact on QoL are more severe in haemophilia patients who have developed inhibitors than in those without inhibitors. [source] Force fluctuations during the Maximum Isometric Voluntary Contraction of the quadriceps femoris in haemophilic patientsHAEMOPHILIA, Issue 1 2007L.-M. GONZÁLEZ Summary., In the general population, the degenerative processes in joints are directly related to adult age, and osteoarthrosis represents the most frequent musculoskeletal alteration. In the haemophilic patient, the degenerative processes in the joint begin at very early ages, and are directly related to musculoskeletal bleeding episodes, which are occasionally subclinical and constitute haemophilic arthropathy. In the haemophilic patient, arthropathy constitutes the most frequent, severe and disabling pathology, and its assessment includes muscular force-related parameters. We have studied the value of Maximum Isometric Voluntary Contraction in the quadriceps femoris of 46 subjects, 28 haemophiliacs (16 severe, eight moderate and four mild) and 18 healthy individuals with a view to establishing appropriate values of force and to restoring physical therapy recommendations. The maximum force values were significantly greater (P < 0.001) in the healthy individuals group. The mild haemophiliacs group also presented significant differences of force (P < 0.05) in relation to the severe and moderate haemophilic patient groups. The mild and severe haemophilia patients presented greater fluctuations of force (P < 0.001) than the control group, the haemophilia group have a minor skill to produce constant force. The seriousness of the arthropathy in the knee is directly related to diminished values of maximum force. Our work evidences that patients with severe haemophilia present a greater degree of arthropathy in relation to moderate and mild haemophilia patients. Haemophilic arthropathy is associated with muscular atrophy and strength deficit. In haemophilic patients, the deficit of maximum force and the presence of fluctuations may suggest an increased risk of bleeding during physical activities and the need to programme specific physical therapy guidelines which increase muscular power through resistance training. [source] The Colorado Haemophilia Paediatric Joint Physical Examination Scale: normal values and interrater reliabilityHAEMOPHILIA, Issue 1 2007M. R. HACKER Summary., ,Persons with haemophilia often experience their first joint haemorrhage in early childhood. Recurrent bleeding into a joint may lead to significant morbidity, specifically haemophilic arthropathy. Early identification of the onset and progression of joint damage is critical to preserving joint structure and function. Physical examination is the most feasible approach to monitor joint health. Our group developed the Colorado Haemophilia Paediatric Joint Physical Examination Scale to identify earlier signs of joint degeneration and incorporate developmentally appropriate tasks for assessing joint function in young children. This study's objectives were to establish normal ranges for this scale and assess interrater reliability. The ankles, knees and elbows of 72 healthy boys aged 1 through 7 years were evaluated by a physical therapist to establish normal ranges. Exactly 10 boys in each age category from 2 to 7 years were evaluated by a second physical therapist to determine interrater reliability. The original scale was modified to account for the finding that mild angulation in the weight-bearing joints is developmentally normal. The interrater reliability of the scale ranged from fair to good, underscoring the need for physical therapists to have specific training in the orthopaedic assessment of very young children and the measurement error inherent in the goniometer. Modifications to axial alignment scoring will allow the scale to distinguish healthy joints from those suffering frequent haemarthroses. [source] Health economics of treating haemophilia A with inhibitorsHAEMOPHILIA, Issue 2005C. KNIGHT Summary., Haemophilia is a rare, inherited blood disorder in which blood clotting is impaired such that patients suffer from excessive internal and external bleeding. At present there is no cure for haemophilia A and patients require expensive, life-long treatment involving clotting factor replacement therapy. Treatment costs are perceived to be higher for patients who have developed inhibitory antibodies to factor VIII, the standard therapy for haemophilia A. However, initial cost analyses suggest that clotting factor therapy with alternative haemostatic agents, such as recombinant activated factor VII or activated prothrombin complex concentrate, is no more expensive for the majority of haemophilia A patients with inhibitors than for those without inhibitors. With the availability of effective alternative haemostatic agents, orthopaedic surgery for haemophilia A patients with inhibitors is now a clinical option, and initial cost analyses suggest this may be a cost-effective treatment strategy for patients with inhibitors whose quality of life (QoL) is severely impaired by joint arthropathy. In an era of finite healthcare resourcing it is important to determine whether new treatments justify higher unit costs compared with standard therapies and whether such higher costs are justified from an individual perspective in terms of improved QoL, and from a societal perspective in terms of improved productivity and reduced overall healthcare costs. This paper examines current data on the health economics of treating haemophilia A patients with inhibitors, focusing on the overall costs of clotting factor replacement therapy and the cost consequences of joint replacement. [source] Variability in clinical phenotype of severe haemophilia: the role of the first joint bleedHAEMOPHILIA, Issue 5 2005K. van Dijk Summary., To quantify variation in clinical phenotype of severe haemophilia we performed a single centre cohort study among 171 severe haemophilia patients. Age at first joint bleed, treatment requirement (i.e. annual clotting factor use), annual bleeding frequency and arthropathy were documented. Because treatment strategies intensified during follow-up, patients were stratified in two age groups: patients born 1968,1985 (n = 91), or 1985,2002 (n = 80). A total of 2166 patient-years of follow-up were available (median 12.0 years per patient). Age at first joint bleed ranged from 0.2 to 5.8 years. Patients who had their first joint bleed later needed less treatment and developed less arthropathy. In patients born 1968,1985 during both on-demand and prophylactic treatment, the 75th percentile of annual joint bleed frequency was consistently four times as high as the 25th percentile. In both age groups variation in annual clotting factor use between 25th and 75th percentiles was 1.4,1.5 times for prophylaxis and 3.8 times for on-demand treatment. To conclude, the onset of joint bleeding is inversely related with treatment requirement and arthropathy and may serve as an indicator of clinical phenotype. Thus, providing a starting point for aetiological research and individualization of treatment. [source] A new magnetic resonance imaging scoring method for assessment of haemophilic arthropathyHAEMOPHILIA, Issue 4 2004B. Lundin Summary., In a European multicentre study, 39 ankles in 28 haemophilic boys were investigated by magnetic resonance imaging (MRI). A new MRI score was developed in the format A(e:s:h) for evaluating haemophilic arthropathy. This scheme provides high resolution and allows separation of different pathological components. The factor A is calculated as the sum of scores for subchondral cysts (maximum value 6), irregularity/erosion of subchondral cortex (maximum 4) and chondral destruction (maximum 6); e, s and h, respectively, represent effusion/haemarthrosis, synovial hypertrophy and haemosiderin deposition, and they are separately evaluated on a scale of 0,4. Working independently, two radiologists scored the 39 ankles twice using both this new ,European' scoring method and a previously published ,Denver' scoring scheme. Final classification was achieved by consensus. The reproducibility of the readings was assessed, and for both scoring methods the results indicated good or moderate intraobserver agreement, and good, moderate or fair interobserver agreement. These findings suggest that MRI can be useful for semiquantitative evaluation of haemophilic arthropathy, providing the examination is performed according to an appropriate protocol, and the images are evaluated by specially trained radiologists. [source] Experimental haemophilic synovitis: rationale and development of a murine model of human factor VIII deficiencyHAEMOPHILIA, Issue 3 2004L. A. Valentino Summary., Haemophilia is a genetic disease as a result of the deficiency of blood coagulation factor VIII or IX. Bleeding is common, especially into joints where an inflammatory, proliferative synovitis develops resulting in a debilitating arthritis, haemophilic arthropathy. The pathogenesis of blood-induced haemophilic synovitis (HS) is poorly understood. The gross, microscopic and ultrastructural changes that occur in the synovial membrane following human and experimental hemarthrosis have been described. Repeated episodes of bleeding induce synoviocyte hypertrophy and hyperplasia, an intense neovascular response and inflammation of the synovial membrane. The component(s) in blood that initiates these changes is(are) not known, although iron is often proposed as one possibility. Here, we describe a novel murine model of human haemophilia A, which facilitates the examination of large number of animals and tissue specimens. The effects of hemarthrosis on the physical, gross and microscopic changes evoked following joint bleeding are described. Controlled, blunt trauma to the knee joint consistently resulted in joint swelling because of a combination of bleeding and inflammation. Hemosiderin was found in the synovial membrane. Similar to hemarthrosis in human haemophilia, joint bleeding resulted in acute morbidity evidenced by inactivity, weight loss and immobility. With time the animals recovered. The model of experimental murine HS described here has utility in the study of the pathogenesis of HS. This is the first of a series of articles, which will discuss the pathophysiology and characterize the model, with comparison of his model to others which have been published previously. It should provide a useful model to test potential therapeutic interventions. [source] Prophylactic therapy for haemophilia: early experienceHAEMOPHILIA, Issue 2003E. Berntorp Summary., During the 1960s, it was reported from Sweden that haemophiliacs with factor levels above 1% rarely develop arthropathy. This observation suggested that severe haemophilia could be converted to a milder form by regular infusions with factor concentrate. After several earlier publications, a report was published in 1992 that detailed 25 years' experience with prophylaxis in 60 patients from the Malmö centre. The results showed that starting prophylaxis early in life with a dose regimen that would prevent factor VIII or IX plasma levels from falling below 1% could prevent the development of haemophilic arthropathy. Also, older age groups who had received less intensive treatment, and who started prophylaxis later in life, were still in a much better condition than historic controls. In the 1970s several small but well-controlled studies from the USA, Germany and Italy clearly showed the benefit of prophylaxis in reducing bleeding frequency. Early experience from the Netherlands was published in 1971. Since these early studies, the results have been corroborated from many countries and in a large multinational study. Although the benefits of prophylaxis seem unquestionable, several research questions remain to be better elucidated, such as when to start and when to stop, dosing and dose interval, and how to assess the long-term treatment effects. These issues are of great economic importance, and the need for health economical studies is obvious. [source] | |||||||||||||