Acquired hemophilia A following SARS-CoV-2 infection and vaccination: clinical summary and insights.

BACKGROUND: Acquired hemophilia A (AHA) is a bleeding diathesis caused by antifactor (F)VIII antibodies produced spontaneously or in response to triggers such as infections, autoimmune disorders, and malignancies. Recently, SARS-CoV-2 exposure, through both infection and vaccination, has emerged as a potential trigger. OBJECTIVES: This is the first systematic review to compare cases of AHA following both SARS-CoV-2 infection and vaccination, presented alongside an illustrative case of severe AHA following SARS-CoV-2 infection during the Omicron variant outbreak. This is also the first study to explore the potential for molecular mimicry between SARS-CoV-2 spike protein (S) and human FVIII. METHODS: A systematic review of AHA cases associated with SARS-CoV-2 infection (n = 14) or vaccination (n = 28) was conducted. An in silico analysis was performed to compare surface epitopes between SARS-CoV-2 S and human FVIII. RESULTS: AHA following SARS-CoV-2 infection or vaccination presented in individuals aged >60 years, with a significantly more rapid onset and potentially milder anti-FVIII response following vaccination. Spontaneous hemorrhagic shock was observed exclusively in AHA following infection. In silico analysis revealed 2 shared surface epitopes between SARS-CoV-2 S and FVIII, one of which is specific to the Omicron variant. CONCLUSION: AHA following SARS-CoV-2 exposure is an emerging trend that may become more prominent with newer variants, highlighting the need for improved clinical characterization and earlier intervention. Preliminary evidence of shared surface epitopes between FVIII and SARS-CoV-2 S supports further investigation of molecular mimicry, and the identification of variant-specific epitopes offers insights into possible differences in immunogenicity between variants.