AstraZeneca COVID-19 vaccine causes very rare blood clots, EU regulator says

The COVID-19 vaccine made by AstraZeneca and the University of Oxford can sometimes cause unusual blood clots, accompanied by abnormally low platelets — the small blood cells involved in clotting — according to an investigation by the European Union's European Medicines Agency (EMA).

These rare blood clots and low platelet counts should be listed as possible side effects of the vaccine, Emer Cooke, the EMA's executive director, said at a news conference April 7, according to Science Magazine correspondent Kai Kupferschmidt. People receiving the shots should remain aware of these potential side effects, particularly within the first two weeks of their vaccination, she said, according to CNN.

Despite the blood clot risk, the investigation "has confirmed that the benefits of the AstraZeneca vaccine in preventing COVID-19 overall outweigh the risks of side effects," Cooke said.

However, the EMA does not yet have the data to say that's true for all groups of people, Sabine Straus, the chair of Pharmacovigilance Risk Assessment Committee (PRAC), said at the news conference. When asked whether the vaccine's risks may actually outweigh the benefits in certain age groups, Straus said, "At the moment that's something that's very difficult to answer because the clinical trials ... we do not have all the age stratified data available," according to CNN.  

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In its investigation, PRAC thoroughly reviewed 62 cases of cerebral venous sinus thrombosis, in which clots form in the venous channels that drain blood from the brain, CNN reported. They also analyzed 24 cases of splanchnic vein thrombosis, in which clots form in one or more veins in the abdomen, such as those connected to the liver and spleen.

These cases were reported to the EU drug safety database, and 18 were fatal, Straus said. And as of April 4, "34 million people were vaccinated in the European Economic Area, and the U.K." (The European Economic Area includes members of the European Union as well as Iceland, Liechtenstein and Norway.)

The overall frequency of the conditions have been difficult to assess, but Straus said that she estimates that "approximately one in 100,000" people vaccinated with AstraZeneca shots may be affected. The reported rate of cases may vary depending on how good the reporting system is in a given country and how well the cases are diagnosed and identified, so the exact rate still needs to be confirmed, she noted.

The U.S. Advisory Committee on Immunization Practices (ACIP) has also been on the lookout for any blood clots related to the mRNA COVID-19 vaccines developed by Moderna and Pfizer — two of the three COVID-19 vaccines approved for emergency use in the U.S. along with the Johnson & Johnson vaccine. With more than 50 million shots in arms, the rate of blood clots among vaccinated people in the U.S. does not appear higher than that seen in the general population, according to a report released March 1. That data suggests these rare side effects seem uniquely linked to the AstraZeneca vaccine, and not to either mRNA-based vaccine. 

PRAC could not definitively pinpoint any specific risk factors, such as age, sex or previous history of blood clots, that may make someone prone to the rare clotting disorders that seem to be linked to the AstraZeneca vaccine, Cooke said. However, she also said that, so far, most of the reported cases have occurred in women younger than 60 years old and within two weeks of vaccination, according to CNN. 

More research will be needed to confirm whether the side effects truly are more common in women, or if there are other risk factors at play.

Related: Quick guide: COVID-19 vaccines in use and how they work 

Similarly, "the currently available data did not allow us to identify a definite cause for these complications," Straus said. "Plausible explanations have been put forward," she said. 

For instance, the vaccine may trigger an immune response similar to "heparin-induced thrombocytopenia" (HIT) — a condition in which antibodies generated by the immune system attack key molecules and proteins that would normally regulate blood clotting, Straus said. 

Specifically, these autoantibodies target complexes made up of heparin (a molecule that thins the blood) and platelet factor 4 (a protein secreted by platelets to dial down the effects of heparin), according to a 2007 report in the Postgraduate Medical Journal.  When the antibodies latch onto this complex, they change its physical structure and make it appear "foreign" to the immune system, so the immune system then generates new antibodies to target it. The antibody-coated complex then plugs into a receptor on platelets, pushing the cells into hyperdrive and causing blood clots. 

Researchers in Germany and Norway have reported HIT-like cases in patients vaccinated with the AstraZeneca shots, and they've also identified antibodies that may be to blame for the reaction, NPR reported. 

Alternatively, some scientists think that the vaccine may mess with the so-called complement system,  a part of the immune system which helps to clear away pathogens and infected cells from the body, Science Magazine reported. The spike protein, a structure that sticks off the coronavirus, can bind to the lining of blood vessels and activate this complement system; in some people, the complement system can then end up attacking the blood vessels themselves, leading to blood clots. 

Something similar may be happening in response to the AstraZeneca vaccine, which prompts the body's cells to build spike proteins, Science reported, but that's just a theory for now.

"We can expect that there will be new information and new recommendations as time goes on," Cooke said at the news conference.

In light of the new data, Britain announced that it would offer an alternative vaccine option to adults aged 30 and younger, The New York Times reported. Similarly, Germany stopped distributing the AstraZeneca vaccine to people aged 60 and younger last week, according to CNN. 

Originally published on Live Science.