Inhibitor formation in hemophilia, a T cell–dependent immune response to infused FVIII, involves binding to HLA class II molecules, presentation to CD4+ T cells, and recognition by the T-cell receptor. In the 25% of severe hemophilia A patients who develop inhibitors, it is hypothesized that if the initial interaction of FVIII and CD4+ T cells occurs in the presence of “danger” signals, that is, severe bleeding or surgery, the innate immune response is activated, with up-regulation of immune response to FVIII. Whether this model also applies to inhibitor formation in the aging adult with hemophilia A is not established.