Long‐term outcome of individualized prophylactic treatment of children with severe haemophilia

Abstract

Summary. The development of arthropathy is a serious complication of severe haemophilia. With the use of prophylaxis, bleeds can be prevented and arthropathy delayed. We investigated whether an individually tailored prophylactic regimen can prevent arthropathy and whether it had a similar effect on orthopaedic outcome compared with that of a high-dose regimen. Efficacy was determined clinically and by radiographs of six major joints. Prophylaxis was started in 70 patients at a mean age of 4´1 years. Mean follow-up was 15´6 years (range 8±24´5 years). The mean factor VIII consumption was 2319 IU/kg/year. The mean number of joint bleeds was 3´5/year and the mean clinical score (maximum score 90) was 1´0, with a mean Pettersson joint score (maximum score 78) of 3´0 at a mean age of 13´5 years. In conclusion, long-term, early-onset, individualized prophylaxis in haemophilia is feasible and prevents arthropathy.

Short-Term Exposure of Cartilage to Blood Results in Chondrocyte Apoptosis

“…27,28 The present data suggest that new treatment strategies to prevent joint destruction may be directed toward prevention of apoptosis. The use of nonselective caspase inhibitors might be an approach in this respect.…”

Effects of the factor V G1691A mutation and the factor II G20210A variant on the clinical expression of severe hemophilia A in children results of a multicenter study

“…In addition, the course of bleeding episodes has been controversially discussed with respect to individualized therapeutic regimens employed by the treating hemophilia center. [15][16][17][18][19] Since 1985, patients enrolled from the different pediatric hemophilia treatment centres in Germany have been treated by the same medical teams using the same treatment protocols. Similar to the Canadian hemophilic cohort recently reported, 11 these patients have been on treatment protocols that have remained unchanged with respect to treatment indications and the criteria chosen to treat a bleeding episode on demand or on prophylaxis.…”

The effects of postponing prophylactic treatment on long-term outcome in patients with severe hemophilia

“…Dosage and frequency of prophylactic infusions were increased in case of spontaneous breakthrough bleeds. 12 Treatment was started earlier and intensified over the years. Over the last 3 decades, the use of prophylaxis in this cohort increased from 44% of treatment years in the 1970s, to 78% in the 1980s, and 95% in the 1990s.…”

“…Although prophylaxis was postponed even longer for patients in the last category (Ն 45 joint bleeds before prophylaxis), both their Pettersson scores and clinical scores were comparable to those of patients who started prophylaxis after 15 to 44 joint bleeds. The median Pettersson score for all patients who had at least 15 joint bleeds before prophylaxis was 11 points (IQR [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Analysis of the adjusted effect of the number of joint bleeds before starting prophylaxis on Pettersson scores after 19 years of follow-up showed a 7% higher Pettersson score per 10 extra joint bleeds before prophylaxis (RI 1.07, CI 1.00-1.15, P .14).…”

“…10,11 Since its introduction in 1968, prophylactic treatment for severe hemophilia in The Netherlands has been started at increasingly younger ages but generally after the occurrence of the first joint bleed. 12 Currently, no prospective studies have been performed on when to start prophylaxis. Therefore, we used the historical changes in treatment strategy to perform a retrospective cohort study on the long-term effects of postponing prophylaxis.…”