Advanced bilateral hemophilic arthropathy of the knee: (a) Anteroposterior view; (b) lateral radiograph of the right knee; (c) lateral view of the left knee. As chronic hemophilic synovitis was not controlled, it led to severe joint degeneration (hemophilic arthropathy) eventually
There is a large body of evidence supporting RS in hemophilia (Table 10.1). The largest such study, performed by Rodriguez-Merchan et al. over a 40-year period, comprises more than 500 cases of RS (knee, elbow and ankle) either with yttrium-90 (Y-90) or rhenium-186 (Rh-186). Between one and three injections were performed with a 6-month interval between them . RS was performed under factor coverage to avoid the risk of re-bleeding during the procedure. For the knee, they used Y-90 at a dose of 185 megabecquerels (MBq) – 1.48 mSv. Rh-186 was used for elbows and ankles. Yttium-90 (Y-90) or Rheinum-186 (Rh-186) emit beta radiation, and have a therapeutic penetration power (TPP) of 1 mm (Rh-186) and 2.8 mm (Y-90). The authors performed joint scintigraphy using a small amount of Tc99 (Technetium-99) after the procedure to check the correct distribution of the radioactive material into the joint. After RS, bleeding frequency declined by 65 %. The size of the synovium (on clinical examination and imaging) declined by 30 % and clinical scores improved by 20 %. However, radiological scores did not improve. The rate of complications of RS was 1 %. The most serious complication was septic arthritis which occurred in 1 patient. Other complications included cutaneous burns if the radioactive material was injected out of the joint, and transient inflammatory reactions following injection which are successfully treated with rest and non-steroidal anti-inflammatory drugs. RS was considered an effective option for the treatment of chronic hemophilic synovitis (Fig. 10.2) [33–70].
Main data from the review of the literature on radiosynovectomy (RS) in chronic hemophilic synovitis
Number of joints (patients)
Effect on bleeding
Effect on joint
Replacement therapy was reduced to less than 1/4 and the effect persisted over at least 3 years
Synovitis was cured in 50 % of cases and given a notable improvement in about another 40 %
Ahlberg and Petterson 
RS decreased the bleeding frequency
RS stopped the progress of the arthropathy if applied at an early stage when the arthropathy was still reversible. If RS was begun at a later stage, the arthropathy seemed to progress independently of the effect on the bleeding frequency
4 patients yes, 10 patient no
Frequency and importance of bleeding decreased in all patients
Effect on ROM was best in knees; six of the seven treated improved and one was unchanged. In elbows, flexion-extension was improved in four cases, unchanged in five and decreased in one; pronation-supination was decreased in four cases. ROM was not affected in shoulders and ankles except for internal-external rotation which was improved in two of three shoulders treated
All patients yes
9/13 with 0 joint bleeding for 6 months and 6/9 for 1 year
All patients yes (<10 BU)
11 joints 0 bleeding for 6 months and 6 joints 0 bleeds for 1 year
5 joints good, 1 fair and 11 poor after 18–182 months
54 % resulted in complete cessation of bleeding into the treated joint after the procedure. Of patients 18 years old and younger, 79 % had a greater than 75 % reduction in bleeding incidence, and of patients older than 40 years, only 56 % had a similar reduction
73 % of patients reported improved ROM of the treated joint
Fernandez-Palazzi and Caviglia 
Au-198 and Rhe-186
80 % of excellent results with no further bleeding
Over 80 % of the patients with hemophilia reported a decrease in the number of hemarthroses and 15 % stopped bleeding altogether in the treated articulation
6–28 (15.9 on average)
In latest follow-up, 77 % of patients reported at least a 50 % decrease in bleeding frequency after treatment. The need for antihemophilic factor consumption dropped by about 74 % post-RS
In most of the injected joints, ROM remained stable or improved
Calegaro et al. 
8–34 (20.6 on average)
The reduction in hemarthrosis and use of the coagulation factor was respectively 78 % and 80 % for elbows, 82 % and 85 % for ankles and 30 % and 35 % for knees
Cho et al. 
13.8 on average
The average frequency of bleeding of the elbow joint has decreased from 3.76 to 0.47 times per month, the knee joint from 5.87 to 1.12 times per month, and the ankle joint from 3.62 to 0.73 times per month, respectively
There was no significant improvement of ROM in affected joints
Rodriguez-Merchan et al. 
6–53 (23.7 on average)
443 (345) and 57 repeat RS procedures
Y-90 and Rhe-186
Some patients yes
On average, the number of hemarthroses decreased by 64.1 %
The degree of synovitis showed a reduction of 31.3 %
Turkmen et al. 
5–39 (16.8 on average)
Some patients yes
Joint bleeding was reduced
Radiosynovectomy (RS) of the knee with Yttrium-90 (Y-90) in a case of chronic hemophilic synovitis
Regarding the potential genotoxic effect of RS, no increase in the risk of cancer has been reported in the literature. In 1977, Ahlberg et al. reported chromosome changes in the circulating lymphocytes of patients undergoing Gold-198 (Au-198) RS . However, in 1985 Rivard et al. did not find an increase of chromosome aberrations after 32P RS, reporting <4 % extra-articular escape of radiation compared to intra-articular counts . Several authors have reported chromosomal changes in patients after RS. In 2000, Falcón de Vargas and Fernandez-Palazzi reported reversible premalignant or nonspecific changes in chromosomal structure in the lymphocytes of hemophilia patients after using Au-198, Rh-186, Y-90; such changes persisted in a low proportion of metaphases up to 2 years after injection when 198Au was used . In 2001, Fernandez-Palazzi and Caviglia reported that chromosomal changes could be observed in equal numbers and frequency in patients after RS as in non-irradiated patients. Furthermore, the changes due to the radiation disappeared with time, never reaching more than 2 %, the threshold considered to be dangerous .
The report by Dunn in 2002 alerted the community to the occurrence of two cases of acute lymphocytic leukemia (ALL) in children with hemophilia after P-32 RS . The children, ages 9 and 14 years, developed ALL within 1 year of RS. Although a causal relationship could not be established, the authors recommended the use of RS only in patients with clearly defined risk/benefit situations, e.g. the treatment of synovitis in patients with inhibitory antibodies or in extremely non-compliant patients whose bleeding is not manageable with factor replacement alone.
Following this report, two publications by Turkmen et al. showed that RS with Rh-186 and : Y-90 in hemophilic children did not induce genotoxic effects [37, 38]. The effects of specific isotope doses and the number of RS treatments were analyzed by Infante-Rivard et al. . These authors found no increase in the risk of cancer and there was no dose–response relationship with the amount of radioisotope administered or number of RS treatments. This study provided some reassurance of the safety of the procedure but groups of younger hemophilia patients receiving RS may still need further study. To highlight this position, Silva et al. stated that unresolved questions regarding the safety of radiation exposure argues against the use of RS in children with hemophilia .
The dose of radiation after RS in patients with hemophilic synovitis is minimal and does not approach dangerous levels. The dose of radiation incurred during a single session of RS is less than that received due to natural sources (approximately 2 mSv –millisieverts per year). It is estimated that the lifetime cancer risk increases about 0.5 % with exposures of at least 100 mSv per year. Knee RS in children provides an approximate radiation dose of 0.74 mSv (90 megabecquerels-MBq) . Although two cases of ALL in children with hemophilia treated with RS have been reported, no causal relationship could be established and no further cases have been reported.
The data suggest that the risk of cancer after RS is not increased. The author recommends that clinicians consider RS in children with hemophilic synovitis when the potential benefits are clearly defined, such as in children with inhibitors or in pediatric patients whose recurrent joint bleeding is unmanageable with factor replacement alone. Importantly, in countries where the availability of factor replacement is limited, RS should be considered early in the patient’s clinical course before osteochondral changes are evident. The authors also recommend that clinicians avoid unnecessary radiation exposure whenever possible .
In our practice, AS is indicated after the failure of three episodes of RS with 6-month intervals. In our series, only 28 (6.3 %) joints eventually had to be subjected to AS or total knee arthroplasty (TKA) . We have never used CS because it requires multiple painful weekly injections. Global results of treatment with CS in the literature have been less favorable than with RS .
RS is our first option for treatment of hemophilic synovitis; the procedure is highly cost effective in comparison to AS (€3,000 per injection). Our second-line therapy is AS (€ 60,000 per procedure) .
10.3 Pigmented Villonodular Synovitis (PVNS)
Pigmented villonodular synovitis (PVNS) is a rare proliferative process of the synovium which most commonly affects the knee (Fig. 10.3) and occurs in either a localized (LPVNS) or a diffuse form (DPVNS). The effect of different methods of surgical synovectomy (either AS or open synovectomy, OS) and adjuvant radiotherapy on the rate of recurrence is unclear [8–32]. While there are several studies of synovectomy in PVNS, most are small series. Table 10.2 summarizes main data in patients with PVNS of the knee according to the literature.
Clinical view of the knee of a patient with pigmented villonodular synovitis (PVNS): (a) lateral view; (b) superior view
Main data in patients with pigmented villonodular synovitis (PVNS) of the knee according to literature on the topic
Mean age (years)
Mean follow-up (years)
Mean recurrence rate (%)
Mean complication rate (%)
Mean development of OA rate
De Carvalho 
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