Optimizing efficacy of factor VIII prophylaxis for severe haemophilia A

Prophylactic replacement therapy is very effective in preventing bleeds and arthropathy in patients with severe haemophilia. Both patient-related and external factors that affect bleeding should be considered to optimize treatment. Prophylaxis is most effective in preventing arthropathy when started early, before the third joint bleed and/or before the age of 3 years. Bleeding phenotype is best characterized by the age at onset of joint bleeding: joint bleeding before the age of 1.8 years is associated with a more severe bleeding type. Pharmacokinetics should be considered as factor VIII half-life increases with age and low trough levels on prophylaxis are associated with increased bleeding. As physical activity promotes well-being and joint health, prophylaxis should be targeted to cover peaks in physical activity. Young children have a shorter half-life and less structured physical activity patterns, therefore they need more intensive treatment and close monitoring. In conclusion, to optimize prophylactic replacement therapy, treatment should be started as soon as possible after the first joint bleed or significant soft tissue bleed. Consequently, bleeding phenotype, physical activities and pharmacokinetics should be taken into consideration to determine the frequency and dose of prophylaxis. Individualization should continue throughout life, as physical activities and pharmacokinetics change with age.