RESUMEN
The infusion of plasma-derived or recombinant factors to treat bleeding disorders such as hemophilia A and B is a success story in the management of a chronic disease. The effectiveness of this approach is however limited by challenges with adverse effects of treatment. The most notable of these are the development of inhibitory antibodies that target the protein therapeutic. The current standard of care for management of hemophiliacs is prophylactic treatment that includes frequent infusions of a Factor VIII product. Failure to comply with the prophylactic regimen is a major hurdle in the management of these patients. We discuss here more recent findings that argue for a pharmacogenetic approach to understanding (and eventually circumventing) immunogenicity. We also review strategies used to bioengineer coagulation factors to extend the half-lives of coagulation proteins. The rapid progress in the last few years to bioengineer coagulation factors in different ways to attain this goal is described. Finally, novel technologies and potential products are emerging that utilize synthetic molecules in lieu of replacement proteins obviating the limitations associated with replacement therapies.