Blood clots linked to AstraZeneca vaccine stem from rare antibody reaction

Two reports published Friday in a leading medical journal help to explain how AstraZeneca’s COVID vaccine can, in rare cases, cause serious and sometimes fatal blood clots.

>>Denise GradyThe New York Times
Published : 9 April 2021, 08:19 PM
Updated : 9 April 2021, 08:23 PM

Scientific teams from Germany and Norway found that people who developed the clots after vaccination had produced antibodies that activated their platelets, a blood component involved in clotting. The new reports add extensive details to what the researchers have already stated publicly about the blood disorder.

Why the rare reaction occurred is not known. Younger people appear more susceptible than older ones, but researchers say no preexisting health conditions are known to predispose people to the problem, so there is no way to tell if an individual is at high risk.

Reports of the clots have already led a number of countries to limit AstraZeneca’s vaccine to older people, or to stop using it entirely. The cases have dealt a crushing blow to global efforts to halt the pandemic, because the AstraZeneca shot — easy to store and relatively cheap — has been a mainstay of vaccination programs in more than 100 countries.

A nurse fills a syringe with a dose of the AstraZeneca vaccine against the coronavirus disease (COVID-19) in Belgrade, Serbia, March 25, 2021. Reuters

Regulators in Europe have emphasised that the clotting disorder is rare, and that the vaccine’s benefits far outweigh its risks. But when a side effect has the potential to be devastating or fatal — like the blood clots in the brain linked to this vaccine — some regulators and segments of the public find the risk unacceptable, even if it is extremely rare.

As of Sunday, European regulators had received reports of 222 cases of the rare blood-clotting problem in Britain and the 30-nation European Economic Area (the European Union plus Iceland, Norway and Liechtenstein). They said that about 34 million people had received the AstraZeneca vaccine in those countries, and that the clotting problems were appearing at a rate of about one in 100,000 recipients.

European regulators said that as of March 22, they had carried out detailed reviews of 86 cases, 18 of which had been fatal.

The safety bar for vaccines is set high because they are given to healthy people. The seemingly greater vulnerability of younger people to the clotting disorder is of particular concern because their risk of severe illness from COVID itself is lower than that in older people. Those differences suggest that overall, compared to older people, younger people may have less to gain and more to lose from the AstraZeneca vaccine.

Germany, the Netherlands, the Philippines, Portugal and Spain have recommended that the AstraZeneca vaccine be given only to people over 60. Canada and France have limited it to those over 55; Australia, over 50; Belgium, over 56. Britain, where the vaccine was developed, has been its staunchest defender, but announced Wednesday that it would begin offering alternative shots to people under 30.

Cameroon, the Democratic Republic of Congo, Denmark and Norway have stopped using the vaccine.

Full vaccination with the AstraZeneca vaccine requires two doses, but regulators in France have recommended that people under 55 who have had one dose get a different vaccine for their second shot.

The AstraZeneca vaccine is not authorised for use in the United States, but the Food and Drug Administration is reviewing data on it to determine whether it should be.

On Wednesday, the European Medicines Agency said that the vaccine’s labelling should be revised to include listing the clotting disorder as a “very rare” side effect of the vaccine.

A vial with the AstraZeneca's coronavirus disease (COVID-19) vaccine is pictured in Berlin, Germany, March 16, 2021. Reuters

In a statement on its website, AstraZeneca said it was “actively collaborating with the regulators to implement these changes to the product information and is already working to understand the individual cases, epidemiology and possible mechanisms that could explain these extremely rare events.”

The two new reports were published by The New England Journal of Medicine. One from Germany describes 11 patients, including nine women ages 22 to 49. Five to 16 days after vaccination, they were found to have one or more clots. Nine had cerebral venous thrombosis, a clot blocking a vein that drains blood from the brain. Some had clots in their lungs, abdomen or other areas. Six of the 11 died, one from a brain haemorrhage.

One patient had preexisting conditions that affected clotting, but during a news briefing Friday, Dr. Andreas Greinacher, an author of the report, said those conditions most likely played only a minor role in the disorder that occurred after vaccination.

All the patients, as well as 17 others with clots after vaccination whose blood was tested, had antibodies known to activate platelets.

The antibodies led to a condition called thrombotic thrombocytopenia, which causes both clotting and abnormal bleeding. The researchers suggested naming the newly identified version in these patients “vaccine-induced immune thrombotic thrombocytopenia.”

The article described specialised blood tests that can be used to diagnose the disorder, and suggested treatment with a blood product called intravenous immune globulin, which is used to treat various immune disorders. Drugs called anticoagulants, or blood thinners, can also be administered in some cases, but not a commonly used one, heparin — because the vaccine-related condition is very similar to one that occurs, rarely, in people given heparin.

The second report, from Norway, described five patients, one male and four female health care workers ages 32 to 54, who had clots and bleeding from seven to 10 days after receiving the AstraZeneca vaccine. Four had severe clots in the brain, and three died. Severe headaches were among their early symptoms. Like the German patients, all had high levels of antibodies that could activate platelets.

The team from Norway also recommended treatment with intravenous immune globulin. The researchers said the disorder was rare, but “a new phenomenon with devastating effects for otherwise healthy young adults,” and they suggested that it may be more common than previous studies of the AstraZeneca vaccine had indicated.

On Friday, European regulators also said they were reviewing reports of a few blood clot cases that occurred in people who had received the Johnson and Johnson vaccine. In the United States, federal agencies are investigating reports of a different type of unusual blood disorder involving a precipitous drop in platelets that emerged in a few people who had received either the Pfizer-BioNTech or Moderna vaccines.

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