Prophylaxis for severe hemophilia: experience from Europe and the United States

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.