Radioisotope Synovectomy for Treating Chronic Synovitis in Inhibitor Patients with Hemophilia.

Hemophilic arthropathy, caused by chronic synovitis is the most common musculoskeletal complication of recurrrent hemarthrosis in hemophilia patients. However, in patients with target joints and chronical synovitis, local directed therapy is more useful than systemic treatment. Radioisotope Synovectomy (RS) consists of destruction of synovial tissue by intra-articular injection of a radioisotope agent. RS has gained acceptance worldwide for 10 years after favourable reports in respect of efficacy and safety. The most frequent and serious complication in hemophilia-A is the development of inhibitors. Due to problems for hemostasis and limited treatment modalities, arthropathy risk is higher in these patients. For last 6 years, we have performed 163 RS procedures in 109 children and young adults in our center. In this report, we present our experience in inhibitor patients (16 cases and 28 joints). All cases were severe hemophilia-A (FVIII<2%). Thirteen patients had high responder (HR)(5–400 BU/ml), three had low responder (LR)(2–5 BU/ml) inhibitor. All patients had target joints and grade-II (n=8) and grade-III (n=20) synovitis. We have used intra-articularly 5 mCi Yttrium 90 for knees (n=16) and 2 mCi Yttrium 90 (n=7) or Rhenium 186 (n=5) for small joints (Schering-CIS, France). The age range was 3–26 years (mean 14.6±6.1yr). We have 4 patients below 10 years. The knees injected 16, elbows 7, ankles 3 and shoulders in 2 joints. Written informed consent was mandatory. For HR patients; recombinant FVIIa (Novoseven) was used (90 mcg/bw / in 2-h interval) in three consecutive doses except one case for 15 joints in 9 patients. Activated PCC (FEIBA) was used (75 IU/bw / in 12 h of interval) in 2 or 3 consecutive doses for 4 patients in 8 joints. High dose FVIII were used for 3 LR patients in 5 joints. Overnight hospitalization was applied. Mean follow-up period after procedure was 2.5 years (range: 6 month-5 year). The efficacy of procedure was evaluated by comparing joint bleedings and signs for synovitis. Seventy-five percent of inhibitor patients had satisfactory results. Pre-procedure joint bleeds were 7.9±3.2 (range: 4–16) for 6 months. After RS, during the first year hemarthroses were significantly decreased as (0.4±1.1). In cases with grade-II synovitis outcome was more better than grade-III synovitis as expected. In two patients, procedure was needed to be repeated due to insufficient effect. After repeated applications, outcome was satisfactory. In other two patients, late recurrence of synovitis was observed after 2 years. One of them, intra-articular injection was repeated and synovitis has improved. No complications have seen. Recently, some suspicions arose due to two children who had had the radioisotope synovectomy using with P32 subsequently developed acute leukemia (ALL) in the USA. However, we have used Y90 and Re186 and no malignancy have reported in the literature and not observed in our study group for 6 years. In conclusion, RS is efficient also in inhibitor patients as far as other patients. RS is cost-effective and easy to perform and hence highly recommended for inhibitor patients. RS seems to be invaluable for treatment of chronic synovitis of inhibitor patients for preventing hemophilic arthropathy.