Scheme of proposed procoagulant mechanisms in VITT. Early reactions: Initial VITT reactions are triggered by complexes formed by PF4 and vaccine constituents and are accompanied by an inflammation-induced “danger signal.” Both events occur early following vaccination (days 1-2). Late reactions: In some vaccine recipients, PF4/vaccine-induced activation of B cells produces high-titer anti-PF4 autoantibodies that bind to platelets and induce platelet activation. Anti-PF4 antibodies together with platelets activate granulocytes (neutrophils) to release procoagulant NETs (NETosis), culminating in VITT-associated thrombosis.