Chronic Haemophilic Synovitis Research Articles

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.
 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.
 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<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<0.001), and knee flexion increased from 84.6±26.22 to 114±21.58 degrees (p<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.
 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<0.005). The Karnofsky and Lansky performance scales were also improved at 6 months follow up ( p<0.005). There was no significant difference between percentage of range of motion measured before and after the therapy ( p>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.

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.

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.

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.

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.

Orthopedic disorders of the knee in hemophilia: A current concept review.

The knee is frequently affected by severe orthopedic changes known as hemophilic arthropathy (HA) in patients with deficiency of coagulation factor VIII or IX and thus this manuscript seeks to present a current perspective of the role of the orthopedic surgeon in the management of these problems. Lifelong factor replacement therapy (FRT) is optimal to prevent HA, however adherence to this regerous treatment is challenging leading to breakthrough bleeding. In patients with chronic hemophilic synovitis, the prelude to HA, radiosynovectomy (RS) is the optimal to ameliorate bleeding. Surgery in people with hemophilia (PWH) is associated with a high risk of bleeding and infection, and must be performed with FRT. A coordinated effort including orthopedic surgeons, hematologists, physical medicine and rehabilitation physicians, physiotherapists and other team members is key to optimal outcomes. Ideally, orthopedic procedures should be performed in specialized hospitals with experienced teams. Until we are able to prevent orthopedic problems of the knee in PWH will have to continue performing orthopedic procedures (arthrocentesis, RS, arthroscopic synovectomy, hamstring release, arthroscopic debridement, alignment osteotomy, and total knee arthroplasty). By using the aforementioned procedures, the quality of life of PWH will be improved.

Efectos clínicos y funcionales de la radiosinoviortesis en pacientes con sinovitis crónica hemofílica. Un estudio prospectivo. Nivel de Evidencia: IV

BackgroundThe joint haemarthrosis is the most common manifestation in patients with haemophilia, whereas radioisotope synoviorthesis (radiosynoviorthesis) is a widely used procedure for the treatment of chronic synovitis in order to prevent progression to a chronic arthropathy. There are no available reports of the clinical or functional outcomes of patients undergoing radiosynoviorthesis. The aim of this study was to describe the sociodemographic characteristics and clinical and functional response of patients with chronic haemophilic synovitis in which radiosynoviorthesis was performed. MethodsBetween January 2010 and December 2012 in a high complexity centre, all patients with chronic haemophilic synovitis that received radiosynoviorthesis as a treatment were included in a prospective cohort. The joint function Gilbert scale for haemophilia patients was applied to each patient, identifying sociodemographic, clinical and functional features prior to the procedure. A minimum follow-up of one year after the intervention was achieved for each patient, when the Gilbert scale was applied once again to determine the functional outcome of the involved joint. ResultsThe mean functional Gilbert scale score was 7.95 before the procedure, and 5.53 after the procedure representing statistical significance (P=.002). The improvement mainly depends on three characteristics: the frequency and haemarthrosis characteristics, the presence of joint effusion, and pain. Other variables measured by the scale of Gilbert Scale remained almost constant after the procedure. DiscussionWe found an improvement in the scale of Gilbert after the procedure, with significant difference mainly pain control (P=.005) and episodes of hemarthrosis. An improvement in the number and characteristics of haemarthrosis was observed in 84% (P=.001) of patients. These results are encouraging for the use of radiosynoviorthesis as a very good alternative for the treatment of haemophilic patients with chronic synovitis.Evidence Level: IV.

Radiosynovectomy in haemophilia: Long-term results of 500 procedures performed in a 38-year period

BackgroundRadiosynovectomy (RS) can reduce the number of haemarthroses in chronic haemophilic synovitis. The purpose of this study was to assess the effectiveness of RS in terms of the objective improvement of five parameters (number haemarthroses, articular pain, degree of clinical synovitis, clinical score of the World Federation of Haemophilia (WFH), and radiological score of the WFH. MethodsIn a 38-year period (1976-2013), five hundred radiosynovectomies were performed in 443 joints of 345 patients with haemophilia diagnosed with chronic synovitis. The mean patient age was 23.7years (range, 6-53). The mean follow-up was 18.5years (range: 6months-38years). The RS was carried out with either yttrium-90 or rhenium-186. We performed 1 to 3 injections (RS-1, RS-2, RS-3), with a 6-month interval between them. ResultsRS resulted in significant improvement in all the parameters studied, except in the WFH radiologic score that showed no improvement. On average, the number of haemarthroses decreased by 64.1% and articular pain decreased by 69.4%. The degree of synovitis showed a reduction of 31.3%. The WFH clinical score revealed an improvement of 19%. The WFH radiological score showed no improvement. There were four complications (0.9%) of RS. Twenty-eight (6.3%) joints eventually had to be subjected to arthroscopic synovectomy or total knee replacement (TKR). No cancer was observed in this group of patients during the 38-year period. ConclusionsRadiosynovectomy (RS) is an effective, safe, minimally invasive, well tolerated procedure in the long-term for the treatment of chronic haemophilic synovitis. Moreover, it is very easy to perform. The knee required more injections than the elbow or the ankle and more severe synoviums required a higher number of RS procedures.

A Technical Complication of Radiosynovectomy in the Ankle

Chronic hemophilic synovitis due to intra-articular bleeding in hemophilia A (a congenital coagulation defect) is a common manifestation. Radiosynovectomy is used for the ablation of chronic hemophilic synovitis. Complications due to radiosynovectomy may be seen, such as leakage of radioactivity to the lymph nodes, liver, and spleen via the lymphatic system. We report herein 2 cases that developed leakage to the distal tibiofibular syndesmosis, lymph nodes, liver, and spleen after radiosynovectomy to the ankles. In order to prevent leakage, low-volume injection is recommended.

Radionuclide synovectomy in haemophilic joints

Chronic synovitis often occurs in people with haemophilia. Untreated chronic haemophilic synovitis affects the metabolism of chondrocytes, thus leading to haemophilic arthropathy. A recently introduced therapeutic protocol includes radiation synovectomy (RS), a safe and cost-effective therapeutic method, which has given satisfactory results in 75% of haemophiliacs with chronic hypertrophic synovitis. Because of its efficacy, we will discuss additional recommendations on the use of RS as a method of choice. The focus of this review is haemophilic arthropathy treatment, including its aetiopathogenesis, reasons for RS indication and its mechanism of action, and use of radioisotopes and other agents for treatment.

Effect of Pulsed Ultrasound using Ketoprofen Gel in Children with Chronic Haemophilic Synovitis of the Knee Joint

Introduction: Chronic knee synovitis (45%) is one of the most common musculo-skeletal complications in haemophilia. However for, chronic synovitis there is aspiration, debridement and synovectomy, which are the expensive procedures. These are invasive procedures, which carry risk in paediatrics population. Also clotting factor replacement is expensive. So in developing countries like India, there exists, need to treat these children without factor replacement and surgery cover due to socio-economic reasons. Thus this study intended to evaluate the effect of pulsed ultrasound using ketoprofen in reducing pain and increasing range of motion (ROM) of the knee joint which inturn is helpful in improving activities of daily living and would be cost effective. Materials and Method: The study was conducted on 10 children in the age group of 4-14 years with chronic haemophilic synovitis of the knee joint. They were evaluated pre- and post-intervention for intensity of pain, ROM and functional activity along with swelling diameter. They received pulsed ultrasound with ketoprofen with following parameter intensity of 1.5W/m2, pulsed mode, 1:1 ratio, frequency 1 MHz for 8 min/day for 15 days. Results: Intra group analysis was done for the Visual Analogue Scale using Wilcoxon Signed Rank test with mean reduction 0.86±0.63. The mean increase in ROM was 3.11±2.69 and in Lower Extremity Functional Scale was 1.2±1.08 which was statistically significant (p Conclusion: Pulsed ultrasound with ketoprofen gel helps in reducing pain, increase ROM and improves functional activities of daily living in children with chronic haemophilic synovitis of the knee joint.

Consecutive radiosynovectomy procedures at 6-monthly intervals behave independently in haemophilic synovitis.

Previous studies on the same group of patients investigated here demonstrated the effectiveness of radiosynovectomy in the treatment of chronic haemophilic synovitis even if one, two or three radiosynovectomy procedures (RS-1, RS-2, RS-3) may be necessary. The purpose of this study was to determine whether the joints' response to each radiosynovectomy procedure behaved independently or not. One hundred and fifty-six radiosynovectomies were performed in 104 joints of 78 people diagnosed with chronic haemophilic synovitis. The patient's mean age was 18 years. Fifty-eight patients required radiosynovectomy in a single joint, whereas 20 received treatment in more than one joint. Of the 104 joints subjected to radiosynovectomy, 33 were elbows, 47 knees and 24 ankles. Radiosynovectomy was carried out with either yttrium-90 or rhenium-186 (1-3 injections with 6-month intervals between them). Of the 104 joints, 68 required a single injection of the radioisotope (RS-1), 20 required two injections (RS-2) and 16 required three injections (RS-3). In eight cases (7.6%), the affected joints eventually required surgery. An analysis of seven variables (number of bleeding episodes, articular pain, range of motion in flexion and extension, muscle strength in flexion and extension, and synovial thickness by imaging) demonstrated that each consecutive radiosynovectomy behaves independently in haemophilic synovitis. Each consecutive radiosynovectomy behaves independently in haemophilic synovitis. This finding had not been documented in the literature before the present study.

Radiosynoviorthesis in people with haemophilia.

In the last three decades radiosynovectomy (RSV) has been partially accepted as an alternative to surgical synovectomy in cases of haemophilic arthropathy. This issue of the journal contains an interesting article1 on the use of RSV in haemophiliacs by a Spanish group with experience in this technique2. RSV was first used by Fellinger et al. in 1952 in patients with rheumatoid arthritis3 and the technique has now been exploited for more than 50 years to treat resistant synovitis in patients with this form of arthritis. It is well known that about 90% of people with severe haemophilia experience chronic degenerative joint changes by the second or third decades of their lives. Such degenerative changes are mainly due to spontaneous recurrent intra-articular bleeding in patients undergoing on-demand treatment and a critical point for avoiding haemophilic arthropathy is the prevention of articular haemorrhages by means of prophylactic treatment. However, despite regular infusions of antihaemophilic concentrate at an early age (primary or secondary prophylactic treatment), recurrent haemarthrosis and chronic arthropathy still persist in adult patients treated on-demand as well as in a small proportion of patients on prophylaxis even in the absence of clinical evidence of bleeding4. Synoviorthesis with radioisotopes has some advantages over the same technique using chemical agents. These advantages are mainly related to the reduced number of injections, usually only one, although in some cases up to three as described in the paper published in this issue1, compared to five to ten, which are the norm with chemicals, as reported by Radossi et al5. The paper by De la Corte-Rodriguez et al.1 describes the possibility that further improvements can be achieved by using more than one radioisotope injection and that the results, in terms of relief of pain, increased range of movements and decreased haemarthrosis, are obtained by the cumulative administrations which seem to work “independently”. This approach needs optimal safety precautions. Indeed, although much has been learnt from thousands of administrations in patients with rheumatoid arthritis, RSV is not widely used in the management of haemophilic arthropathy as it is considered to be potentially dangerous because of the isotopes. Furthermore, some logistic difficulties may be encountered in relation to, for example, drug supplies and inadequate space for the procedure to be carried out in designated protected areas. Further caution is required in haemophiliacs because of the young age of the patients and there are also concerns about the risk of chromosomal damage. Even though long-term monitoring has not detected this adverse event in any haemophiliac who has undergone RSV, these concerns probably explain why there is only limited experience of RSV in Europe and in North America as opposed to Latin America and developing countries. Radossi et al. have demonstrated the successful treatment of end-stage arthropathy using chemical synoviorthesis even in advanced age. Although the average age of the cohort described by the Spanish group in this issue of the journal was 18 years1, the patients’ ages ranged from 18 to 51 years old and the cohort probably included a proportion of patients with advanced stage arthropathy: the overall results of the study would, therefore, support the use of RSV in this subset of patients. The current, ideal treatment of haemophilic arthropathy is primary prophylaxis but unfortunately, only 15–20% of the world’s population has access to this, meaning that 80–85% of haemophiliacs in the world are presently treated on-demand or even untreated. RSV is a relatively simple, virtually painless and inexpensive technique for the treatment of chronic haemophilic synovitis, even in patients with inhibitors. In conclusion, we strongly support the spread of use of RSV and we invite doctors dealing with haemophilia to address frequent logistic difficulties (e.g. legal restrictions, poor appeal) in order to adopt this technique, especially in the current climate of cost-saving and resource limitation, as underlined in the paper by De La Corte-Rodriguez et al1.

Opinions on radiosynovectomy for chronic haemophilic synovitis: point/counterpoint

Joint bleeding is the hallmark of severe haemophilia and the major cause of disability in patients with this coagulopathy. Repeated bleeding into the same joint can lead to chronic synovitis and progressive arthropathy. Radiosynovectomy is one option for the treatment of chronic haemophilic synovitis, but concerns about the risks of exposure to ionizing radiation have divided clinicians as to the safety and appropriate use of the procedure. This article presents two differing viewpoints, one from a pair of orthopaedic surgeons who collectively have performed more than 300 radiosynovectomies in patients with haemophilia. They maintain that radiosynovectomy is a simple, effective, safe and low-cost technique children and adults with chronic haemophilic synovitis. The other perspective is from an experienced haemophilia treater who directs a major US haemophilia treatment centre. She believes that unresolved questions about the safety of radiation exposure in children argue against the use of radiosynovectomy in paediatric patients with haemophilia.

Musculo-Skeletal Complications of Hemophilia

Prophylactic treatment from ages 2 to 18 years could avoid the development of hemophilic arthropathy if the concentration of the patient’s deficient factor is prevented from falling below 1% of normal. A review of the literature on the musculo-skeletal complications of hemophilia has been performed. Early treatment is of paramount importance because the immature skeleton is very sensitive to the complications of hemophilia; severe structural deficiencies may develop quickly. Major hemarthrosis (including joint aspiration) and chronic hemophilic synovitis should be treated aggressively to prevent hemophilic arthropathy. For the treatment of chronic haemophilic synovitis, radiosynovectomy should always be indicated as the first procedure. If, after three procedures with 6-month interval, radiosynovectomy fails, an arthroscopic synovectomy must be indicated. When advanced hemophilic arthropathy is present with severe disability, the aim should be to restore function. Arthroscopic joint debridement is an effective method to achieve this goal and can be considered to be an alternative to total joint arthroplasty in the younger age groups. Finally total joint arthroplasty can usually be relied upon to restore both mobility and function in a diseased joint. The potential benefits of joint arthroplasty must though always be weighed up against the long term sequelae, especially loosening and consequent revision surgery. A correct surgical haemostasis must be achieved by the infusion of factor concentrate at the right dose. Prophylactic treatment from ages 2 to 18 years could avoid the development of hemophilic arthropathy if the concentration of the patient ’s deficient factor is prevented from falling below 1% of normal. Major hemarthrosis, chronic hemophilic synovitis and the initial stages of hemophilic arthropathy should be treated aggressively to prevent hemophilic arthropathy. Finally total joint arthroplasty can usually be relied upon to restore both mobility and function in a diseased joint. A correct surgical haemostasis must be achieved by the infusion of factor concentrate at the right dose. doi:10.4021/jh18e