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Further structural understanding of fVIII immunogenicity may result in the development of more effective and safe fVIII replacement therapies. Preoperative frailty is strongly associated with postoperative complications and mortality. However, the pathways between frailty, postoperative complications, and mortality are poorly described. The authors hypothesized that the occurrence of postoperative complications would mediate a substantial proportion of the total effect of frailty on mortality after elective noncardiac surgery.