H. M. Van Den Berg

Summary. Published retrospective reports from France, the Netherlands and Sweden were analysed for data relating to the long‐term outcomes (primarily the development of arthropathy) of three regimen...

Since the late 1950s, prophylactic therapy has been used in patients with severe hemophilia in order to convert their phenotype into the phenotype of moderate hemophilia. In the early years, prophylaxis was mostly started after the development of arthropathy. This secondary prophylaxis decreased the number of bleeds but did not halt the development of arthropathy. With the start of primary prophylaxis, however, it was shown that both joint bleeds and arthropathy could be prevented. Although its benefits have been proved, prophylaxis has been used as standard treatment for children in only few countries. There are now favorable results with prophylaxis on bleeding and arthropathy with more than 25 years of follow-up. In general, the strategies used for prophylaxis can be divided into those that are targeted at preinfusion clotting factor levels of > 1% and those that are guided by clinical bleeding patterns of individual patients. In both types of strategies, treatment should be started early, before the start of joint damage. However, clotting factor consumption in the first group of strategies is expected to be higher, whereas bleeding frequencies are expected to be slightly lower. The differences in long-term outcome between both strategies may only become apparent after more than two decades. In addition, some patients may be able to stop taking prophylaxis in adulthood while maintaining a low bleeding frequency. In conclusion, although the optimal prophylactic regimen is still under debate, it is well established that prophylaxis reduces or even prevents joint bleeds and hemophilic arthropathy. Therefore, prophylaxis should be offered to all children with severe hemophilia, at least until adulthood.

Summary. Both Sweden and the Netherlands have a long experience with primary prophylaxis in children with severe haemophilia. In these countries it has been offered to all children for the last 3–4 decades. In Sweden prophylaxis is generally started at an earlier age with a higher dosage and frequency than in the Netherlands. Patients in the Netherlands receive a more individually tailored regimen, with prophylaxis now started after the first one or two joint bleeds and dosages are increased when breakthrough bleeds occur. The current study evaluated the effect prophylaxis on long‐term outcomes and the consumption of clotting factor concentrates in Dutch and Swedish cohorts. Our results show that the orthopaedic outcome in the oldest groups of patients from Sweden and the Dutch cohorts were comparable, although the Swedish patients used twice as much clotting products per year. In the youngest patients, joint status is very good and further follow‐up is necessary to demonstrate the benefits of either strategy. In conclusion, more individually tailored regimens aimed at preventing bleeding prevent joint damage in children with severe haemophilia, while clotting factor consumption is about half of that in previously described regimens.

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.

Summary. Port‐A‐Caths have been used increasingly in children with severe haemophilia. In non‐inhibitor patients where Port‐a‐Caths were used to facilitate long‐term prophylaxis, the infection rate is rather low and ranges in the various studies from 0 to 29%, with a median follow‐up time of about 27 months. Patients that received the Port‐A‐Cath for the induction of immune tolerance (inhibitor patients) have a high infection rate of 50% to 83%. Although this percentage is high, good venous access is extremely important, especially in this group. The number of both inhibitor and non‐inhibitor patients in the studies are very small, and a prospective survey is important to obtain more adequate data.