Haemophilic Synovitis Research Articles

Activated factor X delivered by adeno-associated virus significantly inhibited bleeding and alleviated hemophilic synovitis in hemophilic mice.

In hemophilia, deficiency of factor VIII or IX prevents the activation of the common coagulation pathway, and inhibits the conversion of FX to activated FXa, which is required for thrombin generation. We hypothesized that the direct expressed FXa has the potential to activate the common pathway and restore coagulation in hemophilia patients. In this study, the cassettes that expressed FXa, FXaop and FXa-FVII were packaged into an engineered AAV capsid, AAV843, and were delivered into hemophilia A and B mice by intravenous injection. AAV-FXaop could be stably expressed in vivo and showed the best immediate and prolonged hemostatic effects, similar to those of commercial drugs (Xyntha and Benefix). AAV-FXaop also significantly inhibited bleeding in hemophilia A mice with inhibitors. In addition, FXa expression in joints significantly alleviated the occurrence of hemophilic synovitis. AAV-delivered FXa may be a novel target for treating hemophilic and hemophilic synovitis.

Treatment of Chronic Haemophilic Synovitis with PRP: Clinical and In Vitro Studies.

Intra-articular blood, iron and hemosiderin, hydroxyl radical cytokines, and neo-angiogenesis cause synovial inflammation, which leads to cartilage and joint damage. Platelet-rich plasma (PRP) inhibits most of the mediators that produce and maintain synovitis. We compile here our work showing the clinical effectiveness of intra-articular PRP injections and their potential role in stopping articular cartilage damage due to bleeding and its possible repair. A total of 116 joints, including knees (63%), elbows (19.8%), and ankles (17.2%), were treated with intra-articular injections of PRP. Moreover, we also show here the number of extracellular DNA traps (ETs) and the PRP effect in the synovial fluid of patients at the time of treatment and six months after. Clinically, it is demonstrated that PRP is effective in reducing bleeding episodes (p < 0.001) and pain (p < 0.0001) and improving the hemophilia joint health score (HJHS) (p < 0.001) at one year of follow-up. Furthermore, our results demonstrate that PRP inhibits ET formation in vitro and reconstitutes the immune system's cellular components in the synovial fluid of patients after treatment. We conclude that PRP can be considered an effective, safe, and easy treatment for hemophilic synovitis.

Radiosynovectomy in haemophilic synovitis and arthropathy of the knee: A scoping review.

Radiosynovectomy is an established treatment for chronic synovitis in patients with haemophilia. Although its role in rheumatological diseases has diminished, it remains an accepted therapy for haemophilic synovitis. The aim of this scoping review was to map and summarise the evidence surrounding radiosynovectomy in haemophilic knees, identify gaps in the literature and inform future research. Forty-three manuscripts and abstracts were identified for this review. Evidence was limited to observational studies and Yttrium-90 was the most studied licensed radioisotope. Radiosynovectomy was associated with a reduction in bleeding frequency and pain, improvements in range of motion and a reduction in the use of factor replacement. The literature reviewed lacks studies of sufficient methodological quality to permit systematic review and meta-analysis. Systematic review using risk of bias assessment for observational studies should be undertaken to better evaluate the efficacy and safety of radiosynovectomy. A causal relationship between RSV and key clinical outcomes remains undetermined.

The Histopathological Landscape of Synovitis in Hemophilic Arthropathy

Recurrent joint bleeding leads to chronic arthropathy in severe hemophilia A and B. With the recent introduction of novel therapies and the increased availability of treatments for patients with hemophilia, a very tight control of bleeding is achievable, but some patients still experience synovitis oat target joints. A deeper knowledge of the synovial membranes in hemophilic synovitis may help the personalised treatment. However, very few data are available regarding the histopathological characteristics of the synovial membrane of patients with hemophilic arthropathy. We studied the histopathological aspects of the synovial membranes of nine patients undergoing orthopedic surgery in order to describe the overall characteristics and the immune infiltrate. Hematoxylin-eosin coloration was applied. Immunohistochemical analysis was performed and two synovitis scores currently used for rheumatoid arthritis were applied: the Krenn and the Humby scores. Moreover, we evaluated synovial collagen fibrosis by means of Masson trichromic staining, grading subintimal fibrosis semiquantitatively. Iron deposits were parallelly assessed with Perls histochemical stain and graded semiquantitatively. For each case we also evaluated whether iron deposits were mostly found in the intracellular (mainly siderophages) or extracellular compartment. Nine patients (six affected by severe hemophilia A, one by moderate hemophilia A and two by severe hemophilia B) with a mean age of 41 ± 14 years, were included. All patients were in prophylaxis with replacement drugs. Synovial membrane was collected during surgery (four total knee replacement, one arthroscopic knee synovectomy, two total ankle replacement, two arthroscopic ankle debridement), following good clinical practice. Informed consent was obtained before the procedure. All the synovial membrane samples were characterised by synovial hyperplasia and hemosiderin deposits. In seven out of nine samples a pauci-immune infiltrate was observed, whereas in two samples a lymphoid-myeloid infiltrate with lymphoid aggregates was present. All cases showed ≥1 grade fibrosis, with eight out of nine cases showing moderate to severe subintimal fibrosis and only one case with lympho-myeloid infiltrate exhibiting mild fibrosis. Iron deposition across the cohort was heterogeneous, with equal distribution of cases with mild (33%), moderate (33%) and severe (33%) iron deposition. Iron deposits were observed mostly in the intracellular compartment (i.e siderophages) with scattered extracellular presence, with the exception of one case with mild and almost exclusive extracellular deposition. In hemophilic arthropathy, we fount typical characteristics of the blood-induced synovial hyperplasia in the majority of the studied synovial membranes, with a pauci-immune infiltrate resembling degenerative arthropathies such as osteoarthritis. By contrast, lymphoid aggregates similar to inflammatory arthritis were less frequent. Fibrosis and iron deposition were more frequent than in osteoarthritis. It should be noted that all the samples were collected from patients undergoing orthopedic surgery due to long-lasting synovitis. A larger study including patients at different stages of arthropathy may help clarify if a different histopathological landscape may correlate with a different clinical history and predict the response to different therapeutic approaches.

Effect of Radiosynovectomy with Rhenium-188 in the Treatment of Knee Joint Inflammation in Patients with Hemophilia

Background: One of the effective methods to control chronic hemophilic synovitis is radiosynovectomy. Rhenium-188 is a new radionuclide, and its half-life is 0.7 day. This study aimed to investigate the effect of radiosynovectomy with Rhenium-188 on the knee joint of hemophilic patients.&#x0D; Methods: Thirty patients with hemophilic synovitis of the knee visited in the orthopedic clinic in 2019 and 2020, entered the study. They all had at least two bleeding per month; in the supine position with slight knee flexion, after local sterilization, 550 to 750 MBq Rhenium-188 was injected into the knee. A splint was installed for five days. The demographic characteristics, radiography, articular line tenderness, joint line tenderness, flexion and extension restrictions, and joint volume characteristics were evaluated before and six months after injection.&#x0D; Results: The amount of monthly injected factors (VIII and IX) 6 months after injection was decreased from 5260.2±1836 units to 3870.83±1106 units (p&lt;0.001). The radiographic classification has not changed within six months. The average knee pain score decreased from 7.3±1.2 to 2.3±1.1, after six months (p&lt;0.001), and knee flexion increased from 84.6±26.22 to 114±21.58 degrees (p&lt;0.001). None of the patients have experienced complications such as skin necrosis or joint infection. All patients have reported that the pain increases 24 hr after the injection were manageable.&#x0D; Conclusion: The use of Rhenium-188 radiopharmaceutical in radiosynovectomy of 30 hemophilic patients’ knees is effective in reducing pain, tenderness of the joint line, and the number of bleeding episodes, and it improved knee range of motion in the short term (6 months).

Assessment of Joint Health Status of Haemophilia Patients in a Tertiary Care Hospital of Bangladesh

Background: Haemophilia is a sex-linked bleeding disorder. Affected patients suffer spontaneous or post-traumatic bleeding into various sites of the body, mainly into joints, depending on the level of coagulation factor deficiency. Recurrent joint bleeds lead to progressive disability. Susceptibility to joint haemorrhage in persons with haemophilia suggests that the routine assessment of joint health is an important aspect of clinical management and outcome studies assessing the efficacy of treatment. Aim: The aim of the study was to assess of joint health status in haemophilia patients attending in a tertiary care hospital, Bangladesh. Methodology: A descriptive observational study was carried out in the department of Haematology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. A total number of 45 patients who were attended in OPD and IPD, meeting inclusion and exclusion criteria of enrolled haemophilia patients, were included in the study. Joint assessment or any kind of joint impairment was assessed by the Haemophilia Joint Health Score (HJHS) score 2.1 version (an eight-item scoring tool for assessing joint impairments of the six index joints in boys with haemophilia aged 4–18 years. Clinical and laboratory information was recorded with a semi structured questionnaire. Result: Among 45 haemophilia patients, the mean age was 12.9±3.4 years while males were predominant (91.1%). Majority (80.0%) of the patients (36) were diagnosed as haemophilia A. This study observed that, 48.9% of the patients had moderate and 28.9% had severe haemophilia. Knee joint was the predominant target joint. Left knee joint involved in 80% cases and right knee joint were involved in 55.6% of patients. The mean global gait score was found 1.49±0.66 and mean HJHS score was 15.8±4.4. There was no significant correlation between HJHS score and severity of haemophilia (r= -0.081; p=0.596) while significant correlation between the ages of patient with HJHS score (r=0.536; p=0.001) was observed. Conclusion: Haemophilia is a debilitating and life-threatening disease that affects mostly knee, ankle and elbow joints. The joint evaluation system is of paramount importance in clinical practice which is capable to prevent major haemarthrosis and chronic haemophilic synovitis. Haemophilia Joint Health Score (HJHS) is an effective and reliable tool to detect early and subtle changes in joint health and function. This study finding will help in future to assess early the joint conditions and complications, which will assist to modify the treatment approach on demand and start prophylaxis.

Radiosynovectomy for the Treatment of Chronic Hemophilic Synovitis: An Old Technique, but Still Very Effective.

A radiosynovectomy (RS) should be indicated when recurrent articular bleeds related to chronic hemophilia synovitis (CHS) exist, established by clinical examination, and confirmed by imaging techniques that cannot be constrained with hematological prophylaxis. RS can be performed at any point in life, mainly in adolescents (>13−14 years) and adults. Intraarticular injection (IAI) of a radioactive material in children might be arduous since we need child collaboration which might include general anesthesia. RS is our initial option for management of CHS. For the knee joint we prescribe Yttrium-90, while for the elbow and ankle we prescribe Rhenium-186 (1 to 3 IAIs every 6 months). The procedure is greatly cost efficient when compared to surgical synovectomy. Chemical synovectomy with rifampicin has been reported to be efficacious, inexpensive, simple, and especially practical in developing countries where radioactive materials are not easily available. Rifampicin seems to be more efficacious when it is utilized in small joints (elbows and ankles), than when utilized in bigger ones (knees). When RS and/or chemical synovectomy fail, arthroscopic synovectomy (or open synovectomy in some cases) should be indicated. For us, surgery must be performed after the failure of 3 RSs with 6-month interims. RS is an effective and minimally invasive intervention for treatment of repeated articular bleeds due to CHS. Although it has been published that the risk of cancer does not increase, and that the amount of radioactive material used in RS is insignificant, the issue of chromosomal and/or deoxyribonucleic acid (DNA) changes remains a concern and continued surveillance is critical. As child and adulthood prophylaxis becomes more global, RS might become obsolete in the long-term.

Therapy Response of the Yttrium-90 (Y-90) Colloid and Rhenium-186 (Re-186) Sulphur Colloid Radiosynovectomy in Hemophilic Arthropathy

Introduction Radiosynovectomy (also known as radiosynoviorthesis) is a local form of radiotherapy that is used in chronic hemophilic synovitis in the absence of radiological evidence of extensive joint damage and in patients that have failed conservative therapy with clotting factor replacement and physiotherapy. Objectives To evaluate the effectiveness of the Yttrium-90 (Y-90) colloid and Rhenium-186 (Re-186) sulphur colloid radiosynovectomy in hemophilic arthropathy in terms of bleeding frequency, pain score, range of motion and performance score. Methodology This was a prospective cohort trial. A total of 68 hemophilic arthropathy patients who had been treated with radiosynovectomy for knee, ankle, elbow and hip joint were included in this study. Patients were followed up to assess their bleeding frequency, pain score, range of motion of the affected joint and Karnofsky or Lansky performance scale at pre and 6 months post therapy. Result A marked decrease (80–100%) in bleeding frequency was seen in 66.2% of patients, 14.7% of patients had moderate decrease (51–79%) and mild decrease (30–50%) was seen in 14.7% of patients. The frequency of intraarticular bleeding and pain score were significantly reduced at 6 months follow up ( p&lt;0.005). The Karnofsky and Lansky performance scales were also improved at 6 months follow up ( p&lt;0.005). There was no significant difference between percentage of range of motion measured before and after the therapy ( p&gt;0.005). Conclusion Radiosynovectomy is a safe and effective procedure in limiting bleeding frequency, reducing pain and increasing performance scale.

DNA extracellular traps as potential biomarker of chronic haemophilic synovitis and therapeutic perspective in patients treated with PRP: A pilot study.

Hemarthrosis causes chronic haemophilic synovitis (CHS). Although neutrophils are major immune cells infiltrating joints after bleeding, their role on the pathogenesis of CHS is unknown. Neutrophils release extracellular DNA traps (ETs), structures of DNA with bound granular enzymes that were associated with tissue damage. To evaluate the presence of ETs as pathogenic biomarker and the protective effect of intraarticular injection of platelet-rich plasma (PRP) in patients with CHS. Haemophilia Joint Health Score (HJHS) and bleeding episodes (BE) were measured and correlated with ETs indicators (DNA/DNA-Elastase) in synovial fluids (SF), PRP and plasma of 21 patients. Soluble DNA and DNA-Elastase were detected in SF and plasma of patients. The synovial and plasma levels of DNA-Elastase positively correlated with worse HJHS/BE. Interestingly, remaining ETs-inducer factors were present in SF that induced the in vitro release of ETs from blood-isolated neutrophils. This phenomenon was impaired by adding plasma or PRP. Finally, preliminary data obtained from five patients indicate that levels of DNA-Elastase and HJHS/BE decreased after receiving intraarticular injection of PRP. The synovial and plasma levels of DNA-Elastase correlated with worse HJHS/BE suggesting that ETs formation could be a biomarker and potential therapeutic target for CHS. The intraarticular injection of PRP underlined a new potential alternative therapy, decreasing ETs formation in synovia of patients with CHS. However, our hypotheses must be confirmed in the future with better designed and more statistical power studies. Meanwhile, the use of intraarticular injections of PRP for the treatment of CHS remains controversial.

Clinical assessment and point of care ultrasonography: How to diagnose haemophilic synovitis.

The ability of clinical tools to identify early joint changes is limited. Synovitis is a fundamental finding in understanding haemophilia activity and the response to its therapies; thus, there is a need for sensitive methods to better diagnose subclinical synovitis early. Our aim was to compare the frequency with which clinical assessment and ultrasound detected synovial hypertrophy in the most frequently affected joints in patients with haemophilia (elbows, knees and ankles). We analysed patients with haemophilia older than 16 years who came to the haemophilia centre for routine follow-up. From the clinical assessment carried out in the consultation, the swelling, pain and history of haemarthrosis were evaluated and compared with the findings of synovial hypertrophy detected by ultrasound. This comparison was also analysed independently for elbows, knees and ankles. A total of 203 joints of 66 patients with haemophilia (mean age 34 years), most of them on secondary, tertiary prophylaxis or on demand treatment, were included. In joints with swelling, pain and history of haemarthrosis, 78% of the joints showed synovial hypertrophy on ultrasound. However, in joints with no swelling, no pain and no history of haemarthrosis, 40% presented subclinical synovial hypertrophy on ultrasound. This percentage was higher in elbows than in knees and ankles. In adults with haemophilia, physical examination and point-of-care ultrasound study provide complementary data on their joint disease. However, without ultrasound, the ability to detect subclinical synovitis is considerably reduced, especially in the elbows.

Prognostic factors of radiosynovectomy in haemophilia patients with inhibitors: Survival analysis in a 19-year period.

People with haemophilia (PwH) with inhibitors have an increased risk of bleeding and early development of progressive arthropathy. Radiosynovectomy (RS) has been effective in dramatically reducing the frequency of haemarthroses. In the present study, the mid- and long-term results of the efficacy of RS in PwHs with inhibitors and prognostic factors that influence success and failure of RS were presented. Radiosynovectomy was performed in 51 joints of 22 PwHs with inhibitors diagnosed with chronic haemophilic synovitis between January 2000 and December 2018. Two patients were lost to follow-up and four joints were excluded. Number of bleeding episodes within the pre- and post-treatment 6months were documented. Treatment failure was defined as need for repeat RS injection. Results of 47 RS were analysed. The mean bleeding frequency of the joints was 11.2±6.2 (median 9) within the last 6months in the pre-treatment evaluation. After the treatment, the mean bleeding frequency of the joints decreased to 1.2±2.8 (median 0) for first 6months (P<.0001). The cumulative survival rate at 12months was 87% and 78% at 36months. The receiver operating characteristic (ROC) curve analysis revealed that cut-off points of 12 bleeding episodes within the last 6months (sensitivity, 71.4; specificity, 81.8 P=.0022) and an inhibitor titre of 63.4 BU (sensitivity, 57.1; specificity, 75.8; P=.31) were threshold levels for a predisposition for failure. Radiosynovectomy is an effective and safe intervention in PwHs with inhibitors. Bleeding frequency is a prognostic marker for the success of RS treatment. Patients who have more than 12 bleeding episodes within the last 6months before the RS treatment have a higher rate of failure.

EPCR deficiency or function-blocking antibody protects against joint bleeding–induced pathology in hemophilia mice

AbstractWe recently showed that clotting factor VIIa (FVIIa) binding to endothelial cell protein C receptor (EPCR) induces anti-inflammatory signaling and protects vascular barrier integrity. Inflammation and vascular permeability are thought to be major contributors to the development of hemophilic arthropathy following hemarthrosis. The present study was designed to investigate the potential influence of FVIIa interaction with EPCR in the pathogenesis of hemophilic arthropathy and its treatment with recombinant FVIIa (rFVIIa). For this, we first generated hemophilia A (FVIII−/−) mice lacking EPCR (EPCR−/−FVIII−/−) or overexpressing EPCR (EPCR++ FVIII−/−). Joint bleeding was induced in FVIII−/−, EPCR−/−FVIII−/−, and EPCR++FVIII−/− mice by needle puncture injury. Hemophilic synovitis was evaluated by monitoring joint bleeding, change in joint diameter, and histopathological analysis of joint tissue sections. EPCR deficiency in FVIII−/− mice significantly reduced the severity of hemophilic synovitis. EPCR deficiency attenuated the elaboration of interleukin-6, infiltration of macrophages, and neoangiogenesis in the synovium following hemarthrosis. A single dose of rFVIIa was sufficient to fully prevent the development of milder hemophilic synovitis in EPCR−/−FVIII−/− mice. The development of hemophilic arthropathy in EPCR-overexpressing FVIII−/− mice did not significantly differ from that of FVIII−/− mice, and 3 doses of rFVIIa partly protected against hemophilic synovitis in these mice. Consistent with the data that EPCR deficiency protects against developing hemophilic arthropathy, administration of a single dose of EPCR-blocking monoclonal antibodies markedly reduced hemophilic synovitis in FVIII−/− mice subjected to joint bleeding. The present data indicate that EPCR could be an attractive new target to prevent joint damage in hemophilia patients.

Inhibition of Fenton reaction is a novel mechanism to explain the therapeutic effect of intra-articular injection of PRP in patients with chronic haemophilic synovitis.

Haemarthroses cause major morbidity in haemophilia resulting in chronic haemophilic synovitis (CHS) and arthropathy. Oxidation of haemoglobin-coupled iron released in synovium after haemolysis induces chondrocytes death and cartilage damage, allowing postulate using iron-chelating drugs as potential therapeutic tool for haemophilic joint damage. Considering that albumin, the most abundant plasma protein, is a physiologic iron chelator, we aim to demonstrate that impediment of haemoglobin oxidation is exerted by plasma as a mechanism involved in the therapeutic effect of intra-articular injection of platelet-rich plasma in CHS. Oxidation of haemoglobin (Hb) to methaemoglobin (MeHb) through Fenton reaction was induced in vitro by addition of potassium ferricyanide in the presence or absence of peripheral blood-derived platelets-rich or platelets-poor plasma (PRP/PPP) or albumin. The relevance of in vitro findings was analysed in synovial fluid (SF) samples from one patient with CHS obtained before and after 6months of PRP intra-articular injection. MeHb formation was completely impaired either by of PPP, PRP or albumin indicating that PRP exerts an anti-oxidative effect, probably due by plasma albumin. Analysis of SF samples revealed the presence of MeHb levels and haemosiderin-laden macrophages in SF obtained before PRP treatment. Reduction of synovial MeHb, normalization of cellular composition and improvement of health joint haemophilic score, pain and bleeding episodes were registered after 6months of PRP intra-articular injection. Inhibition of Fenton reaction and the consequent normalization of joint cellular composition is a noncanonical mechanism underlying the therapeutic effect of PRP intra-articular injection in CHS.

Chromic phosphate-32 colloid radiosynovectomy for the treatment of haemophilic synovitis: A long-term follow-up study.

We previously reported the outcome of chromic phosphate-32(32 P) colloid synoviorthesis in 53 haemophilic patients with an average follow-up of 31months. The purpose of the present study was the long-term follow-up of the same cohort on both clinical and radiographic features. Nine patients failed to attend the recall appointment. The mean follow-up for the remaining 44 patients (52 procedures) was 15years (range, 14.6-15.5). The mean age at the time of reassessment was 31years (range, 18-43). The haemarthrosis frequency was not statistically significant at the latest follow-up years compared with 31months (0.8 vs 0.4 per week, P=.3). There was no significant change in the clinical severity of haemophilic arthropathy (P=.5). Most of the treated joints still are in stage III of Fernandez-Palazzi and Caviglia classification. There was a trend towards the radiologic deterioration of arthritis with nearly 50% of patients at Arnold-Hilgartner Stage V. 13% of patients underwent a total knee arthroplasty (TKA). The age at which the initial radiosynovectomy was performed was significantly higher in patients who had a TKA than those who had not (22 vs 15years, P<.002). The bleeding control effect of 32P on the target joint remains over time; however, it did not appear to halt the progression of radiographic changes in haemophiliacs. It could delay the need for TKA if it performs at the right time.

Blood-induced bone loss in murine hemophilic arthropathy is prevented by blocking the iRhom2/ADAM17/TNF-α pathway

AbstractHemophilic arthropathy (HA) is a debilitating degenerative joint disease that is a major manifestation of the bleeding disorder hemophilia A. HA typically begins with hemophilic synovitis that resembles inflammatory arthritides, such as rheumatoid arthritis, and frequently results in bone loss in patients. A major cause of rheumatoid arthritis is inappropriate release of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) by the TNF-α convertase (TACE; also referred to as ADAM17) and its regulator, iRhom2. Therefore, we hypothesized that iRhom2/ADAM17-dependent shedding of TNF-α also has a pivotal role in mediating HA. Here, we show that addition of blood or its components to macrophages activates iRhom2/ADAM17-dependent TNF-α shedding, providing the premise to study the activation of this pathway by blood in the joint in vivo. For this, we turned to hemophilic FVIII-deficient mice (F8−/− mice), which develop a hemarthrosis following needle puncture injury with synovial inflammation and significant osteopenia adjacent to the affected joint. We found that needle puncture–induced bleeding leads to increased TNF-α levels in the affected joint of F8−/− mice. Moreover, inactivation of TNF-α or iRhom2 in F8−/− mice reduced the osteopenia and synovial inflammation that develops in this mouse model for HA. Taken together, our results suggest that blood entering the joint activates the iRhom2/ADAM17/TNF-α pathway, thereby contributing to osteopenia and synovitis in mice. Therefore, this proinflammatory signaling pathway could emerge as an attractive new target to prevent osteoporosis and joint damage in HA patients.

Management of Hemophilic Arthropathy of the Ankle.

Hemophilic arthropathy (HA) of the ankle is prevalent in people with hemophilia (PWH). It is frequently severe and incapacitating, due to recurrent bleeding into the ankle articulation during infancy. Around 50% of hemophilic patients suffer from ankle pain and radiological signs of HA. To review current treatment of HA of the ankle in PWH. A literature review of hemophilic ankle arthropathy in PWH was performed utilizing MEDLINE (PubMed) and the Cochrane Library. Primary hematologic prophylaxis could keep away from the development of ankle HA if the level of the patient's deficient factor is prevented from dropping below 1% of normal. Recurrent articular bleeding can be prevented by the intravenous infusion of clotting factor concentrates (prophylaxis). Major articular bleeds and chronic hemophilic synovitis should be managed fiercely to prevent ankle HA. In the circumstance of advancing articular involvement, some noninvasive and invasive procedures can procure symptomatic mitigation and ameliorate the patient's function and quality of life. The ideal treatment for the hemophilic ankle when hematologic prophylaxis fails includes physical medicine and rehabilitation, orthoses, radiosynovectomy, arthroscopic ankle debridement (in the initial stages of cartilage degeneration), and ankle distraction, ankle fusion or total ankle replacement (in advanced stages of cartilage degeneration).

Platelet Rich Plasma for Chronic Synovitis Treatment in Patients with Haemophilia.

Haemophilic synovitis is caused by chronic accumulation of blood in the joint. Conservative treatment is insufficient to solve this pathology. Platelet-rich plasma (PRP) has a high concentration of growth factors (GFs) that play a key role in regulation and stimulation of healing processes. The aim of this study was to describe the effect of PRP injection in chronic synovitis of the joints in patients with haemophilia (PWH). Nineteen patients with 28 joints were treated at our centre in Buenos Aires, Argentina between December 2014 and December 2015. Eighteen were Haemophilia type A (17 severe, one mild) and one was type B severe. Mean age was 26 years old. Chronic synovitis was present in two ankles, seven elbows and 19 knee joints. All affected joints were evaluated for range of motion (ROM), perimeter, Haemophilia Joint Health Score (HJHS), number of bleedings episodes and Visual Analogue Scale (VAS). Evaluations were before treatment and 3 and 6 months after treatment. A mean volume of 4 mL of PRP was injected into the joint cavity. The statistical analysis before and after treatments revealed a statistically significant (P < 0.001) decrease in the HJHS score. Decrease in joint bleeding episodes was also statistically significant (P < 0.001). All patients reported pain relief and VAS scores were statistically significant (P < 0.001). Joint perimeter also showed a statistically significant difference (P < 0.001). No complications were observed in any of the patients, either during blood collection or during PRP injection, even for inhibitor patients. Platelet-rich plasma is a useful, safe, and inexpensive treatment for chronic haemophilic synovitis.

Therapeutic response of radiosynovectomy with p-32 colloid in 326 patients with hemophilic arthropathy

目的观察32P-胶体滑膜切除术治疗血友病性关节病的疗效，并评估MRI Denver评分对血友病性关节病进行分期的临床意义。方法对326例血友病患者的405个关节进行32P-胶体滑膜切除术治疗，根据MRI表现对102个关节进行Denver评分并比较0~6分和7~10分组临床疗效的差异，观察29个膝关节治疗前后滑膜体积变化。结果①全部326例血友病性关节病患者治疗前的疼痛评分为（3.2±2.4）分，治疗后6个月及1、2、3年分别为（1.2±0.6）分（285例）、（1.7±0.5）分（242例）、（2.1±1.1）分（212例）、（2.2±1.6）分（176例），均低于治疗前（P值分别为0.021、0.032、0.030、0.037）。②全部326例血友病患者治疗前的出血频次为（15.1±3.6）次/年，治疗后1、2、3年分别为（2.1±0.7）、（4.3±0.6）、（4.8±0.8）次/年，均低于治疗前（P值分别为0.016、0.011、0.025）。③治疗后6个月及1、2、3年靶关节活动度明显改善的比例分别为68.50%（248/362）、58.39%（181/310）、55.67%（162/239），42.61%（75/176）；Denver评分0~6分组治疗后6个月、1年和2年的HSS评分均高于7~10分组（P值分别为0.011、0.007、0.026）。④Denver评分0~6分组（45个靶关节）治疗前出血频次为（13.0±1.9）次/年，治疗后1、2年分别为（1.3±0.6）、（3.1±0.9）次/年，均低于治疗前（P值分别为0.002、0.009）；Denver评分7~10分组（57个靶关节）治疗前出血频次为（16.6±2.1）次/年，治疗后1、2年分别为（3.1±0.9）、（5.7±1.1）次/年，均低于治疗前（P值分别为0.008、0.004）。Denver评分7~10分组治疗前出血频次与0~6分组差异无统计学意义（P=0.773），治疗后1、2年均高于0~6分组（P值分别为0.028、0.042）。⑤29个膝关节治疗后6个月滑膜体积小于治疗前[（2 362.15±32.41）mm3对（3 012.40±39.78）mm3，t=7.621，P<0.001]。结论32P-胶体滑膜切除术治疗血友病性关节病安全有效。Denver评分0~6分的患者行滑膜切除术治疗效果更佳。

Radiosynovectomy in haemophilic synovitis of elbows and ankles: Is the effectiveness of yttrium-90 and rhenium-186 different?

BackgroundRadiosynovectomy (RS) reduces the number of haemarthroses and the synovial size in chronic haemophilic synovitis. The purpose of this study was to quantitatively compare the effectiveness of two types of RS (yttrium-90 vs. rhenium-186) in terms of the objective improvement of haemarthroses and synovial size. MethodsSeventy RSs were performed in 70 joints (44 elbows, 26 ankles) of 70 haemophiliacs diagnosed with chronic synovitis. Yttrium-90 was used in 21 joints and rhenium-186 was used in 49 joints. The mean patient age was 20.61years. ResultsRS resulted in significant improvement in the three variables studied (six months before RS vs. six months after RS), namely in the number of episodes of haemarthrosis (67.8% improvement); the size of the synovium as measured by means of a clinical scale (43.8% improvement) and imaging techniques in millimetres (26.7% improvement). We did not find significant statistical differences between yttrium-90 and rhenium-186 regarding their efficacy. No correlation was found between the results and other variables: age, joint (ankle or elbow), presence or absence of radiological involvement, type of haemophilia (A or B), grade of haemophilia (mild, moderate or severe), previous haematological treatment (on demand or prophylaxis), and the presence or absence of inhibitor ConclusionsYttrium-90 RS and rhenium-186 RS were equally effective in reducing the number of haemarthroses and the size of the synovium in ankles and elbows in the short-term (6months). No correlation was found between the results and other patients´ characteristics.

Effects of intraarticular (32)P colloid in the treatment of hemophilic synovitis of the knee: A short term clinical study.

Background:Chronic synovitis is a consequence of recurrent intraarticular hemorrhage in patients with hemophilia. Eventually, synovitis leads to degeneration of the articular cartilage, with serious consequences that impact the quality-of-life in hemophiliacs. The aim of our study was to investigate the short term clinical effects of intraarticular injection of the radionuclide preparation32P colloid (32P-labelled colloidal chromic phosphate suspension) on recurrent intraarticular hemorrhages in patients with hemophilic synovitis of the knee.Materials and Methods:Patients who met the inclusion criteria (n = 22) were enrolled in an open-label study between October 2011 and September 2012.32P colloid was injected into the knee joint and patients were followed up over 6 months after treatment. Hemorrhage frequency, visual analog scale pain score, hospital for special surgery knee score, knee circumference, upper knee circumference, knee diameter, and knee range of motion (ROM) were compared before and after treatment with intraarticular32P colloid injection.Results:In 24 knees evaluated in 22 participating patients, there was a significant reduction in the number of hemorrhages after32P colloid treatment, along with significant pain relief. However, there were no statistically significant changes in the degree of joint swelling, degree of muscle atrophy and knee ROM between the pre and post treatment evaluations.Conclusion:The frequency of joint hemorrhage in patients with hemophilic knee synovitis can be significantly reduced and local symptoms can be improved in the short term by intraarticular injection of32P colloid.