Two-step process for VITT pathogenesis. (A) Shortly after vaccine administration, components of the adenovirus vaccine and PF4 generate immune complexes, whereas EDTA sequesters calcium, leading to vascular leak and an inflammatory response serving as a danger signal to provoke antibody generation. (B) One to 3 weeks after vaccine administration, polyanion/PF4/anti-PF4 antibody immune complexes trigger neutrophil extracellular trap formation and platelet aggregation in an FcγRIIA-dependent manner, resulting in thrombosis. Illustration by Alan Hoofring, National Institutes of Health.