Why would a Covid vaccine cause rare blood clots? Researchers have found clues

By Matthew Herper  April 13, 2021

A doctor inoculates someone with AstraZeneca’s Covid-19 vaccine.MICHELE TANTUSSI/GETTY IMAGES

Aweek after receiving the AstraZeneca Covid-19 vaccine, a 37-year-old woman in Norway went to the emergency department with fever and persistent headaches. A CAT scan of her head showed a blood clot in blood vessels involved in draining the brain, but her levels of platelets, involved in clotting, were low. She was treated with platelet infusions and a blood thinner, but had a bleed in her brain the next day. She underwent surgery to relieve the pressure on her brain but died two days later.

This is the side effect, known as cerebral venous sinus thrombosis, that has caused a week of worries around the Covid-19 vaccine developed by AstraZeneca. On Tuesday, the U.S. government said that it had seen the same effect six times among the 6.8 million people given a dose of a similar vaccine, from Johnson & Johnson, and that it recommended a pause on use of that vaccine “out of an abundance of caution,” while researchers investigated.

The news puts a spotlight on the question of whether and how these vaccines are causing this side effect.

The woman in Norway was one of 16 patients described in two different papers in the New England Journal of Medicine that not only described cerebral venous sinus thrombosis, but also offered a partial explanation for why it might be seen in rare cases tied to the AstraZeneca vaccine. The papers likened the condition to the one doctors sometimes see in patients treated with heparin, one of the most common and potent blood thinners. There, too, patients have low platelets and blood clots.

“It’s extremely convincing,” said David Juurlink, the head of the division of Clinical Pharmacology and Toxicology at Sunnybrook Health Sciences Centre in Toronto. He was not involved with the research and, like others interviewed for this story, spoke before the U.S. recommended a pause on the J&J vaccine.

Most tellingly, both the paper from Norway and the second paper, which looked at patients from Austria and Germany, found that blood clots were seen in people who had high levels of antibodies to platelet factor 4, the same types of antibodies reported, infrequently, after treatment with heparin. That doesn’t explain why a vaccine is causing the immune system to produce those antibodies, or whether other vaccines might do the same. But it provides a first step toward explaining the side effect, which experts say is extremely rare, and to looking into whether the same types of rare clots could occur with other shots.

“It’s now a recognized syndrome, a recognized disorder, and most importantly there is a combination of tests that can establish if a patient has this or not,” said Theodore Warkentin, a professor at McMaster University, a co-author of one of the papers and an expert on the rare clots that can be caused by heparin.

The new discovery still raises questions about what, exactly, is going on.

The challenge for public health officials is that these deadly clots occur without vaccines. It’s possible that some people who developed clots after being vaccinated would have developed them even without being vaccinated. So officials have to compare the vaccines against each other, and to try and model the normal rate of clots with low levels of platelets.

On Tuesday, Peter Marks, head of the FDA center that regulates vaccines, said on a call with reporters that there have been no cases of CVST with thrombocytopenia with the Pfizer/BioNTech and Moderna vaccines, indicating that the side effect is not occurring with those vaccines.

Earlier, the European regulators had said it was not clear that the effect existed for any vaccine other than AstraZeneca’s.

“If you look at those reports of blood clots with thrombocytopenia for those other vaccines and then compare them to the background rate we would expect to see, they are not raised,” Peter Arlett, the European Medicines Agency’s head of pharmacovigilance, said at an April 7 press conference.

He gave somewhat mismatched figures — cases of clots worldwide, along with the number of people who received vaccine only in Europe. Still, he said there were 35 cases of serious blood clots with the vaccine made by Pfizer/BioNTech among 54 million doses given; five cases with the Moderna vaccine among 4 million Europeans dosed; and three cases, later updated to four, of blood clots with low platelet counts among 4.5 million people doses — apparently worldwide — with the vaccine developed by Johnson & Johnson. That is the number the U.S. appears to have updated to six cases out of 6.8 million doses.

By contrast, he said, there were 169 cases of cerebral venous sinus thrombosis, and another 53 similar clots in a blood vessel draining the abdomen, among 34 million people.