Prophylaxis in the haemophilia population

Prophylaxis is recommended as preventive therapy for young boys with severe haemophilia in countries where safe factor concentrates are available. This recommendation is supported by results from a randomized, controlled study that compared on-demand therapy with full-dose prophylaxis (Manco-Johnson MJ, Abshire TC, Shapiro AD et al. N Engl J Med 2007;357:535). It is important to distinguish primary vs. secondary prophylaxis. Primary prophylaxis refers to preventive treatment started before the onset of joint damage, whereas secondary prophylaxis refers to treatment started after joint damage has occurred. Whereas the benefits of primary prophylaxis are well documented, data relating to secondary prophylaxis are limited, especially in the adolescent/adult haemophilia population. Failure of prophylaxis may relate to several variables, including: (i) underlying status of the joints; (ii) poor compliance; (iii) participation in high-risk activities and (iv) unfavourable pharmacokinetics (PK), i.e., too rapid elimination of infused coagulation factors. There is evidence that the risk of joint bleeding in individuals with severe haemophilia A relates to time spent with factor levels < 1% (Collins PW, Blanchette VS, Fischer K et al. J Thromb Haemost 2009;7:413); this variable is strongly influenced by frequency of factor infusions and the individual's PK profile. Key ongoing questions relating to prophylaxis include: (1) what is the optimal regimen for initiating primary prophylaxis; (2) role of prophylaxis in the adolescent/young adult haemophilia population and (3) role of prophylaxis in individuals with severe von Willebrand's disease and other rare inherited coagulation disorders. The role of novel long-acting factor concentrates for prophylaxis will also need to be evaluated.