The long and short of it: using the new factor products

Abstract

Hemophilia A (HA) and B (HB) are classified as mild (>5%-40%) moderate (1%-5%) and severe (<1%) disease based on plasma factor activity. Severity of bleeding is commensurate with baseline factor levels in general; however, heterogeneity of bleeding in patients is well described. Recurrent bleeding with painful and disabling musculoskeletal complications is the largest source of morbidity for persons with hemophilia (PWH) but treatment advances through the years has led to improved outcomes. In the early 20(th) century, only whole blood and fresh frozen plasma (FFP) was available to treat bleeding episodes. In 1959, cryoprecipitate was discovered and became an option for treatment of HA in 1965. In the 1970s plasma fractionation led to the first standard half-life (SHL) concentrates. These products ushered in the use prophylactic therapy to prevent bleeding episodes. However, viral contamination slowed the use of prophylaxis until the 1980s when viral attenuation steps increased the safety of plasma concentrates. In the 1990s recombinant concentrates were developed and prophylactic therapy is increasing widely yet not yet universally used. However even with frequent SHL concentrate infusions outcomes are not optimal as PWH spend the majority of time with factor levels below the normal range and are at increased risk for bleeding. In 2014, the first extended half-life (EHL) products were approved for use and have begun to change the landscape of hemophilia care. Challenges of EHL implementation include patient selection, product selection, dose and schedule of infusions, monitoring for safety, efficacy and outcomes, and managing economic aspects of care.