AstraZeneca: What's the deal with thrombosis?

Cerebral venous sinus thrombosis has led to the administration of the AstraZeneca vaccine being halted in many countries. But what exactly are these thromboses? And was the decision to halt the vaccine too hasty?

As of Wednesday, March 31, the AstraZeneca vaccine will no longer be administered to people under the age of 60 — that was the decision reached by the health ministers of Germany's federal and state governments following a recommendation by the country's Standing Committee on Vaccination (Stiko).

Of the 31 cases of rare thrombosis reported to the Paul Ehrlich Institute in Germany, it was determined each person had recently received the AstraZeneca vaccine. In nine cases, the outcome was fatal.

Here's what's known so far about the connection between the two:

Blood clotting in the brain: What exactly was observed?

According to the current status of vaccination monitoring by the Robert Koch Institute (RKI), a German government agency responsible for disease control and prevention, 31 cases of cerebral venous sinus thrombosis (CVST) occurred from 2.7 million first and 767 second doses of the AstraZeneca vaccine. At the same time, 19 of the affected individuals were also found to be deficient in platelets, which can affect blood clotting.

However, this type of thrombosis is considered rather rare, looking at its incidence — it is estimated that two to five people per 1 million experience CVST over the course of a year. However, recent studies indicate a higher number of people affected. As many as 15.7 cases per million people each year have been reported in an Australian study, says Paul Hunter, a professor of medicine at the University of East Anglia in the United Kingdom. That would mean the current incidence is underestimated by four to eight times, according to Hunter.

Does thrombosis always equal thrombosis?

Since Germany's Health Minister Jens Spahn announced a pause in AstraZeneca vaccinations in mid-March, there has been much discussion had — especially on social media. There were many angry responses: why is the contraceptive pill still being prescribed to women, even though it is known that roughly 1,100 women will suffer thrombosis among every 1 million who take it. In comparison, why do authorities throw the entire vaccination strategy out the window after only seven cases of thrombosis in 1.6 million vaccinated people?

Karl Lauterbach, a public health expert from Germany's center-left Social Democrats, criticized this comparison in an interview with German public radio Deutschlandfunk. CVST is not comparable in severity to thromboses caused by the contraceptive pill, he argued.

When people talk about thrombosis in connection with the contraceptive pill, they are usually referring to leg vein thrombosis. In this case, blood clots form within the veins in the legs and, if they break loose, can travel to the lungs and cause an embolism.

But that is not the entire truth. Taking the pill also increases the risk of the more dangerous CVST. "Women are af

fected more often than men, and hormones probably play a role. In late pregnancy, in the puerperium and in women taking the contraceptive pill, we see CVST most frequently," Peter Berlit, secretary-general of the German Society for Neurology, told DW. Regardless of gender, younger people are generally affected more often than older people, he added.

AstraZeneca: Concerns justified?

The decision to refrain from giving the vaccine to people under the age of 60 as a rule, of course, does not come out of the blue. The Stiko had recommended the step on Tuesday, the day before the announcement. The thromboses are rare but serious, it said in a press release. Because they occur predominantly in people younger than 60, the Stiko recommends limiting vaccines administration to people outside that age group.

There's still no conclusive information on how the sinus vein thromboses actually develop and whether there is a connection to the vaccine. Researchers at the University of Greifswald, Germany,had published study results at the end of March in which they described a possible mechanism.

For example, antibodies that activate blood platelets were detected in the blood samples of four individuals who had developed thromboses after being vaccinated with AstraZeneca. This causes the blood to clot and can lead to thrombosis.

These results were published in Research Square, a preprint publication, which means the data has not yet been reviewed by independent experts. But for safety reviews and recommendations by committees such as Stiko, quick results like this may be important.

"The picture is not yet complete, but the question is what preliminary conclusions can be drawn from it," Robert Klamroth, chief physician for internal medicine at Vivantes Hospital in Berlin, said.

He sees the data as strengthening the link between AstraZeneca and thromboses.

"If you consider the large number of vaccinations, it becomes vividly clear how rarely sinus thrombosis occurs and how low the risk is," said Alice Assinger of the Medical University of Vienna in Austria. "Never before have so many people been vaccinated in such a short time, which is what makes the recognition of these rare side effects possible in the first place."

Researchers have long observed that COVID-19 infections, for example, also lead to more frequent thrombosis. This is presumably due to the fact that in the case of COVID-19, our immune system upregulates a certain defense mechanism that influences blood clotting and can thus lead to more thromboses.

Vaccination strategy: Which decision is the right one?

It remains striking that, looking to the United Kingdom, only four explicit cases of sinus vein thrombosis have been reported in the current 13.7 million doses of AstraZeneca vaccine administered. There, the vaccination drive continues without restriction.

"One possible explanation could be that the older groups of people were vaccinated first, and this complication is virtually not observed there. One consequence of this could be to use a different vaccination for women up to 55 years of age in order to keep the number of atypical thromboses as low as possible," said Johannes Oldenburg, chairman of the board of the Society for Thrombosis and Hematosis Research (GTH).

The European Medicines Agency ( EMA) announced renewed consultations on the safety of AstraZeneca's vaccine for next week. Across the EU, 59 cases of sinus vein thrombosis have been recorded in the EudraVigilance database as suspected adverse events. Most recently, the EMA had emphasized in a press release that the benefits of the vaccine outweigh their risks.

There's no word on a possible connection between the other COVID vaccines and any thromboses. "So far, there is no evidence that this complication is clustered with any of the other approved vaccines," Oldenburg said, adding that this question was of course in focus now. "Any newly approved vaccine will certainly be closely monitored in this regard."

What should vaccinated individuals be aware of?

Those who have already received the AstraZeneca's vaccine should watch out for the following symptoms, according to Berlit: "People who have persistent and very severe headaches within the first 2-3 weeks after

vaccination need to get further evaluation." Similarly, pinpointshaped hemorrhages in the skin along with headache may indicate CVST.

For the 2.7 million people who have so far received their first dose of AstraZeneca, the second shot would be due in early May. But what about young women, who under the new circumstances would be considered to be a risk group? The Stiko said in its press release it is working on having a recommendation ready by the end of April.

This article was last updated on March 31, 2021. It was translated from German.

This is how thrombosis shows up in on a CT scan