Scientists at Cardiff University discovered that a protein in blood likes to bind to part of the vaccine, which can lead to dangerous clotting.
Intriguingly, the reaction is not caused by the coronavirus particles contained in the vaccine, but the system used to deliver it inside the body.
The AstraZeneca vaccine encapsulates coronavirus genetic material inside a weakened version of the common cold virus - known as an adenovirus, which infects chimpanzees.
The new study shows that adenovirus attracts a protein called “platelet factor four” to it like a magnet.
This new hybrid protein-virus confuses the immune system, which creates new antibodies, which themselves stick to the proteins, triggering the formation of dangerous blood clots.
The process happens only rarely, explaining why few people are affected by the condition.
The clots have been linked to 73 deaths out of 50 million doses of AstraZeneca in the UK.
Cardiff University received government funding to discover what was causing the clotting. Researchers soon realised that people suffering clots had extra antibodies that were attacking “platelet factor four”.
Professor Alan Parker, one of the researchers at Cardiff University, told BBC News: “The adenovirus has an extremely negative surface, and platelet factor four is extremely positive and the two things fit together quite well.”
He added: “We’ve been able to prove the link between the key smoking guns of adenoviruses and platelet factor four.
“What we have is the trigger, but there’s a lot of steps that have to happen next.”
The AstraZeneca vaccine is believed to have saved more than a million lives around the world and prevented 50 million cases of Covid-19.
“Although the research is not definitive, it offers interesting insights and AstraZeneca is exploring ways to leverage these findings as part of our efforts to remove this extremely rare side effect,” a spokeswoman for the vaccine manufacturer said.
The researchers have so far only shown the binding effect in lab experiments, but say it “provides a mechanism” by which clotting could occur.
They are hoping that their findings could be used to design vaccines that do not trigger this reaction, and so will be safer.
Currently, the AstraZeneca jab is not offered to people under 40 because the risks of blood clotting are thought to outweigh the benefits of the vaccine.
The research was published in the journal Science Advances.