Vaccine-induced immune thrombotic thrombocytopenia is mediated by a stereotyped clonotypic antibody

The syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare thromboembolic complication of adenoviral-vectored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson) mediated by antibodies directed against platelet factor 4 (PF4).1-5 The mechanisms by which the adenoviral DNA vectors break immune tolerance to PF4 and trigger B-cell clonal expansion and secretion of anti-PF4 immunoglobulin Gs (IgGs) are under intense investigation and likely involve formation of immunogenic complexes of PF4 with vaccine components in a proinflammatory setting.6 Pathogenic anti-PF4 IgGs subsequently form circulating immune complexes with PF4 tetramers, which are thought to drive thrombotic events by Fc γ receptor IIa–dependent platelet activation and to activate granulocytes to release procoagulant neutrophil extracellular traps.6-8 Serum anti-PF4 antibodies are mostly transient and appear in serum within days of vaccination, suggesting...