The European and British medicines regulators have found that there is a strong possibility that the Oxford-AstraZeneca vaccine is associated with rare blood clots, but both agencies have insisted that the shot continues to be effective for the vast majority of people.
“What we have learned from the very detailed review of the cases is that there is a strong association with the AstraZeneca vaccine and the adverse events,” said Sabine Straus, who chairs the safety committee of the European Medicines Agency.
The EMA said on Wednesday that as a result of its findings the unusual blood clots should be listed as a very rare side effect of the vaccine. However, the EMA left it up to national health agencies to decide whether it should be restricted to specific age groups.
Britain’s regulator, the Medicines and Healthcare products Regulatory Agency, came to a similar conclusion on Wednesday and the government’s vaccine advisory committee recommended that people between the ages of 18 and 29 should be offered an alternative.
“The balance of benefits and risks is very favourable for older people but it is more finely balanced for younger people,” said June Raine, chief executive of the MHRA. “And we at the MHRA are advising that this evolving evidence should be taken into account when considering how the vaccine is used.”
The announcements mark a further setback for the vaccine, which was developed last year in conjunction with researchers at the University of Oxford and has been rolled out in dozens of countries, including Canada.
The current controversy stems from multiple reports that it has been linked to cerebral venous sinus thrombosis, CVST, a sometimes fatal condition that occurs when clots form in veins that drain blood from the brain. It has also been tied to other clotting events that were coupled with low platelets, which can lead to heavy bleeding. Both types of cases were especially high in younger women.
The vaccine has been suspended for use in Norway and Denmark, while health officials in Canada, France, Sweden, Germany, Estonia and the Netherlands have recommended that it only be used in older people.
The EMA said Wednesday that out of 34 million vaccinations with the AstraZeneca vaccine, it had received 169 reports of CVST and 53 reports of clotting with low platelets. The cases came from across the European Union and Britain, and 18 people had died. Dr. Straus said the reports represented one case for every 100,000 vaccinations.
The MHRA said that out of 20 million vaccinations in the U.K., it had received 79 reports of both types of blood clots – 51 were women and 28 men. A total of 19 people had died and of those 14 had CVST and five had clotting with low platelets. Dr. Raine said the cases amounted to four in one million. The agency said it had not found any clotting cases among the 5.6 million people who have received two doses of the vaccine.
Both agencies stressed that the benefits of the vaccine outweighed the risk for the vast majority of people and that it should continue to be widely available. “This vaccine has proven to be highly effective – it prevents severe disease and hospitalization, and it is saving lives,” said Emer Cooke, the EMA’s executive director.
Researchers believe that the blood clots could be triggered by an immune response similar to what occurs infrequently with a blood thinning drug called heparin – known as heparin-induced thrombocytopenia, or HIT. In the case of HIT, the drug binds to a protein called platelet factor 4. Some people produce antibodies against that combination, leading to out-of-control clotting. Platelets are consumed in the process of forming clots, which ultimately results in a low platelet count.
“You could speculate that maybe when people are making antibodies to some constituent of the vaccine, there is something there that makes them make the unique antibody that also cross reacts with platelet factor 4,” said Beverley Hunt, a professor of thrombosis and hemostasis at King’s College London. “But we don’t know what part of the vaccine might do that.”
Dr. Hunt added that there is a treatment for HIT that involves injecting concentrated antibodies that block the effect of the antibodies causing harm. The same treatment could work in cases involving the vaccine.
While most of the clotting cases involve the AstraZeneca vaccine, there have been some similar events from vaccines that are based on the same type of technology.
The AstraZeneca shot is known as viral vector vaccine, where genetic material from the virus that causes COVID-19 is packaged inside a different, harmless virus. Once injected, the modified virus mimics the COVID-19 virus and triggers the immune system.
The Johnson & Johnson and Sputnik vaccines use a similar platform. The EMA said there have been three rare clotting cases in the J&J jab out of roughly 5.5 million vaccinations. “This is, however, under close scrutiny. The [safety committee] is looking at it carefully, and I think it would be fair to say there’s intensive monitoring of this issue across the vaccines,” said Peter Arlett, who heads the EMA’s Data Analytics and Methods Task Force.
Adam Finn, a professor of pediatrics at the University of Bristol, said the overall risk of the blood clots is extremely low, comparing it with other risks we accept. “We’ve seen data that the annual risk of dying in a car crash if you regularly travel in a car is about one in 20,000, and the lifetime risk is about one in 240,000. We take those risks fore granted,” he said.
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