Assessment of the effectiveness of prophylactic replacement of lower than ‘standard’ doses of clotting factor concentrates in children with severe hemophilia A

Hemophilia is indeed a model disease of hemostasis characterized in its severe form with spontaneous bleeding into muscles and joints. The irony is that in spite of tremendous advances in the understanding of the cause of the disease, including its genetics, and the availability of excellent therapeutic products, the vast majority of people with haemophilia (PWH) in the developing world, do not receive appropriate treatment. While the reasons for this are indeed multiple, the predominant issue is the cost associated with effective treatment protocols. This is because the models of prophylaxis with CFC, which are currently in vogue, the doses of CFC used are much more than what is available or affordable in most developing countries. Thus prophylaxis, the only form of effective treatment for haemophilia, that has been shown to be excellent in preserving good musculoskeletal function over the long term, is not practiced in the vast majority of developing countries. Unfortunately, there is enough data to show that ‘on-demand’ / episodic treatment over a wide range of doses, which is what is predominantly used in these countries, does not maintain musculoskeletal structure or function over the long run. This study is therefore designed to challenge the understanding of doses needed to initiate prophylaxis and show that even at lower doses, it should not only be possible to offer prophylaxis at least to children but also have better long term musculoskeletal outcome. If successful, such data can not only give a new dimension to CFC replacement protocols in developing countries but could also impact practices in other parts of the world.

There is enough long term data on bleed frequency and joint changes with prophylaxis at low doses (weekly dose varying from 15-25 IU/kg) from the van Creveld clinic.(Table 2) (7) These data clearly show that even at those doses, there was significant reduction in the bleeding frequency and joint changes. There is also some recent limited data from China (15) and Sri Lanka (Sudharma Vidyatilake, personal communication) suggesting that even at lower doses, prophylaxis reduces the bleeding frequency in children with severe hemophilia compared to ‘on-demand’ treatment. xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /

The hypothesis for this study therefore is that prophylactic CFC even at lower doses will reduce the bleeding frequency and therefore joint and muscle damage in people with severe haemophilia much more than ‘on demand’ or episodic treatment with similar quantities of CFC. This study is designed to begin to test this hypothesis.