Researchers determine how certain COVID-19 vaccines trigger rare blood clotting reactions

The COVID-19 vaccines from Oxford-AstraZeneca and Johnson & Johnson, both of which use adenoviral vector technology, are associated with rare cases of vaccine-induced immune thrombotic thrombocytopenia or VITT, a bleeding disorder characterized by a low number of blood platelets.

“We don’t know why these rare antibodies form in the first place, and we don’t know why they cause blood clots in unusual places, but we do know the specific target of the VITT antibody,” McMaster researchers said. in the study.

Ishac Nazy, the lead researcher and corresponding author, said some people have formed VITT antibodies after being vaccinated with adenoviral vaccines. These unusual antibodies then bound to a platelet protein in the blood called platelet factor 4 (PF4) “in a very unique and specific orientation”.

Bleeding disorder occurs in 1 in 60,000 AstraZeneca recipients in Canada

Antibodies bring PF4 proteins together to form immune complexes, which bind to and activate platelets and lead to “a self-sustaining vicious cycle of clotting events,” Nazy said in a statement.

The research team used a molecular mapping technique to study the interaction between the VITT antibodies and the PF4 protein, finding the precise location on the PF4 where the VITT antibodies bound.

The study also compared blood samples from five to 10 VITT patients with a similar clotting condition known as heparin-induced thrombocytopenia, or HIT, and found patterns of platelet activation that were distinct from HIT patient samples. This indicates that the tests used to diagnose HIT are not suitable for diagnosing VITT, according to the study.

The study also found that VITT antibodies could bind “very tightly to PF4, more tightly than HIT antibodies”.

Nazy, who is also the scientific director of the McMaster Platelet Immunology Lab, says he hopes the results can help diagnose and treat VITT, as well as make vaccines safer.

John Kelton, study co-investigator and co-medical director of the McMaster Platelet Immunology Laboratory, said the next step is to “develop a rapid diagnosis and an accurate test to diagnose VITT.” Researchers say current rapid tests take time and are prone to false negative results.

“Our major interest now is to go upstream of how clots occur to prevent them from happening,” he said in a statement.

VITT has been observed in one in 60,000 recipients of AstraZeneca in Canada.

Canada’s National Advisory Committee on Immunization recommended last month that provinces stop administering the AstraZeneca vaccine in most cases, adding that it prefers those who received the first doses of AstraZeneca to receive a vaccine. mRNA from Pfizer-BioNTech or Moderna to complete their two-dose series.

In June, the estimated rate of developing VITT after a second dose was one in 600,000.