An international team of researchers in the United Kingdom and United States say they may have identified the reason why some people develop blood clots after receiving the Oxford-AstraZeneca or Johnson & Johnson COVID-19 vaccines.

Around March 2021, reports began to emerge that some younger people were developing a rare form of blood clotting after receiving those jabs.

Some countries responded by restricting the AstraZeneca vaccine, for instance, to people over the age of 60.

Now eight months on, researchers who worked with AstraZeneca and have published their peer-reviewed findings. They believe these viral vector vaccines may be attracting a protein, which may be causing an immune response that's kickstarting a potentially hazardous process — namely, blood clotting.

The protein is known as platelet factor 4 and is otherwise associated with coagulation.

Rare but life-threatening

"Vaccine-induced immune thrombotic thrombocytopenia, also known as thrombosis with thrombocytopenia syndrome, is a life-threatening condition seen in a very small number of people," wrote the researchers in a press release.

Whether it's a "rare" condition is not merely a matter of interpretation.

In October 2021, the British Heart Foundation reported that in the UK, there had been 423 known cases of blood clots after an estimated 24.9 million first doses, and 24.1 million second doses of the vaccine. Of the 423 people who developed blood clots, 72 died. Six of the deaths occurred after the second dose.

There were also some deaths in Germany and Australia.

Findings suggest viral vector

The Oxford-AstraZeneca and Johnson & Johnson vaccines use viral vector technology. 

In that press release, which was published by the University of Cardiff, findings suggest "it is the viral vector — in this case an adenovirus used to shuttle the coronavirus' genetic material into cells — and the way it binds to platelet factor 4 (PF4)" that causes those blood clots.

Adenoviruses are common viruses that cause a range of complaints, from a sore throat to pink eye.

They can also be used as a carrier or vehicle in vaccines — to help deliver just enough information to our immune systems so that they know what coronavirus is and that it needs to be defeated. In this context, they are known as "viral vectors."

In very rare cases, the scientists suggest, "the viral vector may enter the bloodstream and bind to PF4, where the immune system then views [it] as foreign." They believe this misplaced immunity could result in the release of antibodies against PF4, which bind to and activate platelets, "causing them to cluster together and trigger blood clots in a very small number of people after the vaccine is administered."

Why exactly the immune system should view PF4 as a threat is left unexplained. 

DW requested interviews with the lead researchers, Alan Parker at Cardiff Universtiy and Alexander Baker at the Mayo Clinic in Arizona, but they were unavailable to speak or correspond by email at the time of writing.

A potential solution

This is, however, not the first research to focus on the role of PF4 in trying to understand why some people get blood clots after receiving vector-based vaccines.

In April 2021, the European Medicines Agency said it had found a "possible link to very rare cases of unusual blood clots with low blood platelets."

And in May 2021, German researchers said in a pre-print study (not peer-reviewed at the time) that they had detected antibodies against PF4 in people who had received vector-based vaccines.

The difference now is that the Cardiff-Arizona study is peer-reviewed — and that they say they now understand more about why they are seeing PF4 platelets.

They say the viral vector vaccine — also known as ChAdOx1 — has a strong negative charge and that "can act like a magnet and attract proteins with the opposite, positive charge, like PF4." 

Now that they know that, they can start to work on a potential solution.

Lead author Alexander Baker is quoted in the press release as saying that there is "an opportunity to engineer the capsid, or outer shell of the vaccine, to prevent this interaction occurring. Modifying ChAdOx1 to reduce electronegativity may reduce the chance of causing thrombosis with thrombocytopenia syndrome."

A history of learning

This is also not the first time that vaccines have been released into the community and have been found to produce previously rare or unknown health risks, while at the same time protecting people against their intended target; in this case, COVID-19.  

It happened with the early polio vaccine, for instance. Due to a set of circumstances that included poor local sanitation in some communities, the polio vaccine helped eradicate wild polio, but caused a vaccine-derived form of the virus at the same time — which we are still fighting.

What is now known about the rare risk of rare blood clots likewise means scientists can improve the COVID-19 vaccines.

Editor: Fabian Schmidt