New-onset and relapsed thrombotic microangiopathy post-COVID-19 vaccination

Thrombotic microangiopathy (TMA) associated with coronavirus disease 2019 (COVID-19) vaccination has been reported, however, the clinical characteristics and pathogenesis remained mysterious. We reviewed 84 TMA cases post-COVID-19 vaccination, including 64 patients diagnosed with thrombotic thrombocytopenic purpura (TTP), 17 cases presented as atypical hemolytic uremic syndrome (aHUS), and three cases manifested as unclassified TMA. TMA episodes were mostly associated with messenger RNA vaccines. For TTP, 67.6% of females developed symptoms after the first dose of the vaccine, and 63.0% of males were secondary to the second dose (p = 0.015). Compared with TTP, aHUS generally appeared within 7 days (p = 0.002) and showed higher levels of serum creatinine (p < 0.001). 87.5% of TTP received plasma exchange (PEX)-based treatment, and 52.9% of aHUS adopted non-PEX-based therapies (p < 0.001). Mechanistically, complement dysfunction, neutrophil activation, and the generation of pathogenic autoantibodies resulting from molecular mimicry contribute to explaining the pathogenesis of TMA post-COVID-19 vaccination.