15 July 2021

Details of the mechanism behind vaccine-induced immune thrombotic thrombocytopenia (VITT) – a rare side-effect associated with certain COVID vaccines – have been reported for the first time.

A team of scientists at McMaster University in Hamilton, Canada, say their findings could pave the way to better diagnosis and treatment of VITT, as well as prevention.

The research was led by Dr Ishac Nazy, associate professor of medicine and scientific director of McMaster Platelet Immunology Laboratory. “Our work also answers important questions about the connection between antibodies and clotting,” said Dr Nazy, whose research was fast-tracked for publication in Nature.

The study shows, at a molecular level, how unusual antibodies stick to components from blood platelets, which cause them to trigger clot formation.

The team altered the molecular composition of the PF4 protein, which allowed them to identify the binding region on the protein. In doing so, they found the antibodies stick to platelet factor 4 (PF4) protein in a unique and specific orientation, which enables them to align with other antibodies and platelets. This leads to a self-perpetuating vicious cycle of clotting events.

“These disease-causing aggregates quickly activate platelets, creating a highly intense clotting environment in patients,” Dr Nazy added.

Study co-investigator John Kelton, who is co-medical director of the McMaster Platelet Immunology Laboratory, added: “We believe that this study is important because it clarifies how the clotting ensues, and because we have been able to identify the molecules involved.

“The next step is to develop a rapid diagnostic and accurate test to diagnose VITT. Our major interest is now to move upstream from how the clots happen to preventing them from occurring.”

The study also sheds some light on why current rapid tests yield so many false-negative results and allows for new strategies to improve diagnostic testing.


Source:

Huynh A, Kelton JG, Arnold DM, Daka M, Nazy I. (2021) “Antibody epitopes in vaccine-induced immune thrombotic thrombocytopenia.” Nature, doi: 10.1038/s41586-021-03744-4

 

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