Proposed biological mechanisms that influence the immunogenicity of pdFVIII and rFVIII products. Recombinant FVIII products have been associated with a 1.87-fold increase in inhibitor risk compared with pdFVIII. Within the spectrum of rFVIII products, a full-length second-generation rFVIII concentrate has been reported to be 1.6-fold more immunogenic than a full-length third-generation rFVIII product. The potential immunomodulatory components of each concentrate are portrayed here in order of perceived importance. TGF-β, transforming growth factor β.