Optimal treatment strategies for hemophilia: achievements and limitations of current prophylactic regimens by Johannes Oldenburg Blood Volume 125(13):2038-2044 March 26, 2015 ©2015 by American Society of Hematology

The prophylaxis triangle. The prophylaxis triangle. Prophylaxis treatment regimen has 3 main determinants: (1) the given resources/concentrate availability to target a specific trough level and/or intervals of substitutions, which both reflect the costs; (2) the bleeding trigger, which comprises physical activity, presence and degree of arthropathy, and presence of chronic synovitis; and (3) the number of bleeds, especially joint bleeds, that are regarded as acceptable. These 3 determinants form a triangle. If 1 determinant is changed, the other 2 will adjust. With unlimited resources, zero bleeds and normal physical activity may be targeted; with few resources, only 2 low-dose substitutions per week may be given, thus accepting a certain number of bleeds and limited physical activity. Johannes Oldenburg Blood 2015;125:2038-2044 ©2015 by American Society of Hematology

Illustration and schematization of the long-term outcome results. Illustration and schematization of the long-term outcome results. Results of the 2013 study by Krämer et al,20 underlining that progression of joint arthropathy during intensive prophylaxis regimens is a process with subtle progression over years. Scores ≥2 are regarded to be pathological. The ankle joints are the first joints that develop arthropathy after a median time of 10 years, followed by knee joints and elbow joints significantly later. The clinical Gilbert scores are following the Pettersson scores 1 to 2 decades later. The gray area indicates the initial decade of prophylactic treatment when early joint disease remains undetected by the Pettersson score. GS, Gilbert score; PS, Pettersson score. Johannes Oldenburg Blood 2015;125:2038-2044 ©2015 by American Society of Hematology