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NETosis and thrombosis in vaccine-induced immune thrombotic thrombocytopenia

Vaccine-induced thrombotic thrombocytopenia (VITT) is an uncommon but serious adverse event of adenovirus-based COVID-19 vaccines. The elevated mortality rate (between 23 to 40%) has caused vaccine hesitancy, undermining vaccination efforts in many countries.

The condition presents with thrombocytopenia (low platelets), thrombosis (blood clots), and platelet activation, resulting from the action of the anti-platelet factor 4 (PF4).

VITT resembles heparin-induced thrombocytopenia (HIT), which is driven by NETosis (formation of neutrophil extracellular traps - NETs). When activated by pathogens, the neutrophils release these NETs, activating platelets and blood coagulation pathways.

But we still don´t know how these mechanisms influence thrombus formation in VITT. So, researchers at the University of New South Wales investigated blood samples of vaccinated individuals with VITT. The results were published in a preprint report from 2021.

Study Overview

VIIT samples

The researchers collected blood samples from VITT and HIT patients and healthy donors who had received one dose of the vaccine.

NETosis markers

First, they investigated NETosis markers in VITT patients. For that, they assessed the presence of citrullinated histone H3 (CitH3) and cell-free DNA (cfDNA) concentrations in the plasma and the presence of activated neutrophils in the blood.

Results indicated NETosis in VITT patients:

  • VITT patients had higher levels of CitH3 and cfDNA than healthy controls.

  • The fresh blood of VITT patients contained a significant number of activated neutrophils, neutrophil-platelet aggregates, and neutrophils undergoing NETosis

Thrombosis induction

To test if VITT antibodies induce thrombosis, the researchers treated the healthy donor’s whole blood with VITT IgG or normal IgG. After staining the blood, they flowed it through Cellix’s Vena8 Fluoro+ biochip microchannels coated with von- Willebrand factor (vWf).