Lessons from vaccine-induced immune thrombotic thrombocytopenia

Abstract

Adenoviral vector vaccines are effective against SARS-CoV-2 but have been associated with a rare side effect termed vaccine-induced immune thrombotic thrombocytopenia (VITT). Here, we discuss our understanding of how vaccine-induced antibodies to platelet factor 4 (PF4) form immune complexes that activate platelets and trigger the thrombotic events seen in VITT.

Fig. 1. Overview of vaccine-induced immune thrombotic thrombocytopenia.

In most people, administration of an adenovirus-based COVID-19 vaccine induces antibodies to the spike protein of SARS-CoV-2 and protects the recipient against COVID-19 (steps 1–4). In rare cases (step 5), vaccine-induced immune thrombotic thrombocytopenia (VITT) antibodies are induced that can bind to platelet factor 4 (PF4) and form immune complexes that activate platelets (steps 5–7). This leads to pathological activation of clotting cascades and a fall in platelet counts (steps 8–9). VITT-associated clots have been described in the brains, lungs, abdomen, liver and legs (step 10). Image courtesy of Christy Groves, adapted by S. Bradbrook/Springer Nature Limited.