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 gamma receptor IIadependent 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 a recall immune response on memory B cells.(9)