Recombinant Factor VIII Products and Hemophilia A: Efficacy, Safety, and Inhibitor Development

Abstract

This issue of Seminars in Thrombosis and Hemostasis reviews the development, efficacy, safety, and inhibitor formation of the newly manufactured recombinant factor VIII preparations for treatment of hemophilia A. About 50 years ago hemophilic bleedings were managed with whole blood, preferably direct from donor to patient. Fluid overload was at that time a great concern. Once fresh frozen plasma was prepared, it became the treatment of choice because the required factor VIII activity could now be infused in one-half the volume. A major step in volume reduction was the finding that cryoprecipitate contains virtually all of the factor VIII activity present in plasma. The next goal was to remove as many of the nonessential proteins, especially fibrinogen, from the cryoprecipitate, thus creating the first plasma-derived factor VIII concentrates. Then came the time when the transmission of viral contaminants, initially hepatitis B, later HIV, became the greatest concern. This led to ways to make these concentrates relatively virus safe. Although these newer plasma-derived concentrates greatly changed the quality of life for hemophiliacs and changed their life expectancy to almost normal, concerns remained that contaminants, known or not yet known, might have an impact. Once the gene structure of factor VIII was identified, this knowledge was used for developing recombinant products in which either the entire molecule or that part of the structure that contains the biological activity is produced. It is hoped that the possibility of potential viral transmission is abolished with these concentrates, but side effects, especially the concern for inhibitor development, are to be considered. This issue of Seminars in Thrombosis and Hemostasis addresses these problems.