ABSTRACT
ABSTRACT Introduction: The radiosynovectomy (RS) is one treatment option for recurrent hemarthrosis in patients with hemophilia (PWH). A prospective cohort study was designed to evaluate the effects of the RS on the synovial membrane volume in the ankles and knees of PWH and patient characteristics related to the RS outcome. Methods: In a one-year follow-up, 25 joints of 22 PWH who presented 3 bleeds or more in the same joint over the last 6 months (target joints) were subjected to the RS. Two groups were compared: those who retained target joints following the RS and those who did not (less than 3 bleeds/6 months after the RS). The groups were analyzed according to age, hemophilia type/severity, joint, body mass index (BMI), inhibitor and Hemophilia Joint Health Score 2.1 (HJHS). The magnetic resonance images (MRI) of six ankles and six knees were acquired prior to, and 6 months after, the RS. The synovial membrane volume and arthropathy MRI scale were accessed and volumes were compared and correlated with the Yttrium-90 dose injected. Results: Patients with a mean age of 12 years and a mean HJHS of 6.7 (p < 0.05) retained target joints after the RS. The inhibitor, joint, type/severity of disease and BMI showed no significant differences between groups. The synovial membrane volume had a significant reduction after the RS (p = 0.03), but no correlation with the Yttrium-90 dose. In proportion to the synovial membrane volume, doses injected to the ankles were larger than those injected to the knees. Conclusion: The synovial membrane volume is reduced after the RS, regardless of the effective 90Y dose.
Subject(s)
Humans , Child , Adolescent , Adult , Synovitis , Magnetic Resonance Imaging , Synovectomy , Hemarthrosis , Hemophilia A , Joint DiseasesABSTRACT
Objective: To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A (HA) . Methods: Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018. Results: A total of the 381 children were enrolled with 116 (30.4%) mild, 196 (51.4%) moderate, and 69 (18.1%) severe cases; 54 patients (14.2%) had inhibitors, including 22 high and 32 low titer inhibitors. Positive family history was positively associated with inhibitors[P<0.001, OR=3.299 (95%CI 1.743-5.983) ], and high-intensity exposure was associated with inhibitors[P=0.002, OR=2.587 (95%CI 1.414-4.731) ]. High-intensity exposure was associated with high titer inhibitor production[P=0.001, OR=8.689 (95%CI 2.464-30.638) ], and high-intensity exposure increased the risk of high titer inhibitors in HA patients. After inhibitors occurred in 54 patients with HA, the rates of overall joint annual bleeding (z=-3.440, P=0.001) and traumatic annual bleeding (z=-2.232, P=0.026) increased, but the rates of the annual joint bleeding (z=-1.342, P=0.180) and spontaneous annual bleeding (z=-1.414, P=0.157) remained to be not statistically significant. The joint ultrasound score did not change significantly after the inhibitor information (z=-0.632, P=0.527) . Conclusions: Positive family history and high-intensity exposure could increase the risk of F Ⅷ inhibitors in HA patients, and high-intensity exposure increased the risk of high titer inhibitors. The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.
Subject(s)
Child , Humans , Factor VIII/therapeutic use , Hemarthrosis , Hemophilia A/drug therapy , Hemorrhage , Retrospective StudiesABSTRACT
Objective@#To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A (HA) .@*Methods@#Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018.@*Results@#A total of the 381 children were enrolled with 116 (30.4%) mild, 196 (51.4%) moderate, and 69 (18.1%) severe cases; 54 patients (14.2%) had inhibitors, including 22 high and 32 low titer inhibitors. Positive family history was positively associated with inhibitors[P<0.001, OR=3.299 (95%CI 1.743-5.983) ], and high-intensity exposure was associated with inhibitors[P=0.002, OR=2.587 (95%CI 1.414-4.731) ]. High-intensity exposure was associated with high titer inhibitor production[P=0.001, OR=8.689 (95%CI 2.464-30.638) ], and high-intensity exposure increased the risk of high titer inhibitors in HA patients. After inhibitors occurred in 54 patients with HA, the rates of overall joint annual bleeding (z=-3.440, P=0.001) and traumatic annual bleeding (z=-2.232, P=0.026) increased, but the rates of the annual joint bleeding (z=-1.342, P=0.180) and spontaneous annual bleeding (z=-1.414, P=0.157) remained to be not statistically significant. The joint ultrasound score did not change significantly after the inhibitor information (z=-0.632, P=0.527) .@*Conclusions@#Positive family history and high-intensity exposure could increase the risk of F Ⅷ inhibitors in HA patients, and high-intensity exposure increased the risk of high titer inhibitors. The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.
ABSTRACT
Hemophilic arthropathy (HA) is one of the most common and typical manifestation in the course of recurrent bleeding episodes in patients with hemophilia.The main pathogenesis are synovial hyperplasia,inflammation and neovascularization,articular cartilage degeneration and bone injury.Considering its pathogenesis,potential targets for disease modifying therapy in HA are iron,inflammation,vascular remodeling,hyper fibrinolysis,bone remodeling and cartilage regeneration.So far,iron chelators,anti-inflammatory therapy,anti-fibrinolytics and bone remodeling agents have demonstrated beneficial effects,predominantly in a preclinical setting.This article reviews the pathogenesis of HA and identifies potential therapeutic targets to provide more therapeutic options for HA.
ABSTRACT
Hemophilic arthropathy (HA) is one of the most common and typical manifestation in the course of recurrent bleeding episodes in patients with hemophilia.The main pathogenesis are synovial hyperplasia, inflammation and neovascularization, articular cartilage degeneration and bone injury.Considering its pathogenesis, potential targets for disease modifying therapy in HA are iron, inflammation, vascular remodeling, hyper fibrinolysis, bone remodeling and cartilage regeneration.So far, iron chelators, anti-inflammatory therapy, anti-fibrinolytics and bone remodeling agents have demonstrated beneficial effects, predominantly in a preclinical setting.This article reviews the pathogenesis of HA and identifies potential therapeutic targets to provide more therapeutic options for HA.
ABSTRACT
La profilaxis en el tratamiento de la hemofilia ha sido crucial en la mejoría del pronóstico y calidad de vida en las personas con hemofilia (PCH). A pesar de ello, no está globalmente implementado y no ha sido ejecutado satisfactoriamente en Latinoamérica, donde es difícil evaluar la situación, y el manejo de las PCH no se ajusta a los estándares ideales. El grupo GLAITH (Grupo Latino Americano para el Impulso del Tratamiento de la Hemofilia) discutió el problema a través de una encuesta entre sus integrantes. Los hallazgos fueron discutidos en Bogotá en mayo del 2013 en donde los participantes definieron los puntos esenciales a comunicar en un llamado a la acción. Las proporciones de casos de hemofilia A reportados fueron entre 75 y 90% y entre 10 y 25%, los de hemofilia B. La hemofilia grave representó entre el 26 y el 55% de los casos. Un alto porcentaje de PCH tiene artropatía hemofílica. La atención de PCH varía en cada país, sólo se cubre entre el 50 y 60% del tratamiento, que es a demanda en el 85 a 95% de los casos. Sólo 5 a 15% reciben profilaxis, la mayoría secundaria. Pocos países tienen programa nacional o registros homogéneos. En llamado a la acción y conclusión para la región se recomienda: establecimiento de un registro latinoamericano unificado; estudios prospectivos de costo efectividad y evaluación de criterios en profilaxis secundaria; estudios comparativos de calidad de vida, individualización del tratamiento e implementación de la profilaxis en forma global en Latinoamérica.
Prophylactic treatment in the management of hemophilia has been a crucial factor in improving the prognosis and quality of life for people with hemophilia (PCH). However, it is not globally implemented. In Latin America it is difficult to assess the status of PCH and the its management does not conform to ideal standards. The GLAITH group discussed the problem in Latin America. A survey of its members and its findings were discussed at a meeting in Bogota in May 2013. Proportions of hemophilia A and B were 75-90% and 10-25% respectively. Severe hemophilia represents 26-55% of cases. A high percentage of PCH have hemophilic arthropathy. The general care and specific treatments of PCH vary by country, only 50-60% of the treatment is covered and in 85-95% of the cases are performed on an ondemand basis. Just 5-15% receives prophylaxis, most of them secondary. Few countries have a national program or homogeneous records. Finally the GLAITH group proceeded to develop a conclusion and call to action for the region where the following points are recommended: the establishment of a unified Latin American registry; prospective cost-effectiveness studies and evaluation criteria related to secondary prophylaxis; comparative studies of quality of life with and without prophylaxis in the region; promotion of individualization of treatment and, the increase of primary and secondary prophylaxis globally in Latin America.
Subject(s)
Humans , Quality of Life , Hemophilia B/therapy , Hemophilia A/therapy , Primary Prevention/methods , Prognosis , Severity of Illness Index , Secondary Prevention/methods , Latin AmericaABSTRACT
<b>Introduction</b> : The purpose of this study was to clarify the effectiveness of a home exercise (HE) program for hemophilic patients.<br><b>Methods</b> : An intervention study was conducted over twelve weeks for patients aged 16 to 60 years, inclusive. Exercise guidance to assist in the improvement of their knee function was provided to the patients. Using questionnaires and assessments of physical function, we measured the physical condition of the patients before and after HE. Guidance about the strengthening of knee extensor muscles, static stretching of knee flexor muscles and standing balance training, as well as advice for the promotion of physical activities, was provided on an individualized basis. Muscle force and range of motion of the knee, modified Functional Reach (mFRT), 10 meter walking time, and 3 minute gait distance were all measured. All patients were surveyed for bleeding frequency, activities of daily living (ADL), and health related quality of life (HRQOL : SF-36), respectively.<br><b>Results</b> : Twenty-two patients with an average age of 37.2 years, were included in the analysis, with 86.4% of them having a history of severe of hemophilia (coagulation factor level <0.01 IU mL−1). There were significant improvements in strength of knee extensor and range of extension of the knees, mFRT, 10 meter gait time, 3 minute gait distance, ADL, and physical function of SF 36. There was a significant correlation between Ex for locomotive activities and change of 3 minute gait distance. No increase in bleeding frequency was noted.<br><b>Conclusion</b> : HE for hemophilic patients is useful for the improvement of muscle force and range extension of the knees, mFRT, gait speed, and ADL. Individualised guidance for improvement of physical activities and knee function is necessary for improvement of overall physical function.
ABSTRACT
PURPOSE: We designed this study to demonstrate the pathophysiology of hemophilic arthropathy (HA) by creating an animal model for determining the effect of repeated intraarticular bleeding in the synovium and articular cartilage. MATERIALS AND METHODS: 20 normal male New Zealand white rabbits were used for this study. We injected 1 ml of autologous blood from the ear vein of the rabbits into the right knee joint three timeds a week for 18 weeks, and we injected 1 ml of normal saline into the left knee joint three times a week for 18 weeks as a control group. We examined the pathologic changes by microscopy and plain X-ray, and we determined the mRNA expression of proinflammatory cytokines in the synovium of the HA by performing real time RT-PCR at the 11th week and 18th week after starting blood-injection. We also examined the GAG and the PGE2 production in cultured chondrocytes that were extracted from the HA knees. RESULTS: At the 11th week, after blood injection there were no remarkable gross changes in the HA knees and the control knee joints. At the 18th weeks, the experimental knee joints (HA knees) showed grossly swelling and degenerative changes by X-ray. The infiltration of inflammatory cells and the synovial proliferation in the HA knee joints were compared with that in the control knee joints by microscopic examination. The expressions of the mRNA of TNF-alpha, IL-1, MMP-1 and MMP-3 in the HA synovium were increased, as determined by real time RT- PCR, as compared with that in the control knee. In the cultured chondrocytes, the GAG production was decreased and the PGE2 was increased, but the MMP-1 and MMP-3 were not changed, as determined by ELISA. CONCLUSION: Our results showed that the GAG production of chondrocytes of the HA knees was decreased and there was increased PGE2, so that the cartilage degeneration by intra-articular bleeding was caused by the decreased metabolism of chondrocytes rather than by increased catabolism of the chondrocytes. We suggest that HA was associated with synovitis and cartilage degeneration, but decreased cartilage metabolism was the major mechanism of HA.