While COVID-19 vaccines have been deemed safe, one rare side effect is a blood clotting reaction called vaccine-induced immune thrombotic thrombocytopenia (VITT).
VITT involves a drop in the platelet count, termed thrombocytopenia, combined with the formation of clots (thrombosis). VITT is similar to heparin-induced thrombocytopenia (HIT), a syndrome that can develop after the introduction of the anticoagulant heparin.
VITT is known to occur with the AstraZeneca and Johnson & Johnson vaccines, but how the severe clots that characterize VITT develop was unclear. A new study has now shed light on how the vaccines cause blood clots.
The researchers determined that platelets are activated by antibodies in patients with VITT. In rare cases, unusual antibodies to platelets are triggered by the vaccine, and these stick to blood platelet components which cause them to trigger the formation of blood clots.
These antibodies bind tightly to the platelet factor 4 (PF4) protein, with the antibodies only binding to eight surface amino acids, all of which are located in the same location where heparin binds. The researchers found heparin inhibits the binding of the antibodies.
Biolayer interferometry (BLI) was used to determine how tightly VITT antibodies bind to their PF4 target. The researchers found the location and the strength of binding allowed the antibodies to cluster PF4 proteins together, which form immune complexes capable of activating platelets and triggering an intense clotting reaction.
“The antibodies stick to the platelet protein called platelet factor 4 (PF4) in a very unique and specific orientation, which allows them to align with other antibodies and platelets in the precise formation that leads to a self-perpetuating vicious cycle of clotting events,” explained Ishac Nazy, PhD, associate professor of medicine for the Michael G. DeGroote School of Medicine at McMaster University in Ontario, Canada. “These disease-causing aggregates quickly activate platelets, creating a highly intense clotting environment in patients.”
Now that the mechanism involved in blood clot formation has been determined, the researchers are concentrating on potential treatments to prevent clots from forming. It will also be necessary to develop an accurate and rapid diagnostic test that will allow VITT to be diagnosed.
You can read more about the study in the paper – Antibody epitopes in vaccine-induced immune thrombotic thrombocytopenia – which was recently published in Nature. DOI: 10.1038/s41586-021-03744-4