On Monday, Germany, France and Italy joined a group of other European countries that had temporarily stopped administering the AstraZeneca vaccine. The decision came amid a handful of severe blood clotting cases reported in people who had received the vaccine.
While they say stopping AstraZeneca inoculations is a precautionary move, the EMA, which acts much like Australia’s Therapeutic Goods Administration (TGA) in regulating medicine across the European Union, said that severe blood clots weren’t more common among vaccinated people than among the general population.
“The vaccine is not associated with an increase in the overall risk of blood clots (thromboembolic events) in those who receive it. There is no evidence of a problem related to specific batches of the vaccine or to particular manufacturing sites. However, the vaccine may be associated with very rare cases of blood clots associated with thrombocytopenia, i.e. low levels of blood platelets,” wrote the agency after the extraordinary meeting held yesterday.
The World Health Organization shares the same view and has appealed to countries not to pause vaccination campaigns.
Have European countries overreacted, or could there be a possible link between the AstraZeneca vaccine and these cases of blood clots?
Data from AstraZeneca’s clinical trials, which included 24,000 people, reported four blood-clot events in people who received the vaccine and eight in the placebo group. While clinical trials showed the AstraZeneca vaccine is safe, it is still possible that rare side effects occur.
So far, about five million doses have been administered in Europe, and 15 cases of deep-vein thrombosis and 22 pulmonary embolisms have been reported following vaccinations, some with fatal consequences.
On Wednesday, the Paul-Ehrlich-Institut (PEI), the German federal agency and medical regulatory body, reported seven severe cerebral venous sinus thrombosis (CVST) cases. CVST occurs when a blood clot forms in the brain’s venous sinuses, and is associated with platelet deficiency. The individuals were 20 to 50 years old. Three of them subsequently died.
All cases occurred 4–16 days after vaccination with the AstraZeneca vaccine, and this pattern was “flagged” in the surveillance data.
The PEI writes that this number of cases was found to be statistically significantly higher than the number of CVSTs that normally occur in the general population. In 1.6 million people – the number of individuals vaccinated with AstraZeneca in Germany so far – one case of CVST would have been expected in 14 days. Seven were reported in the vaccinated population.
These cases occurred in the younger to the middle-aged population. This caused concern, as age is generally a risk factor for cardiovascular diseases.
The problem is separating cause-and-effect from coincidence.
Every year 1 to 2 people in 1000 develop a dangerous blood clot, and 8% of people develop a blood clot in their lifetime.
Globally, there is evidence that blood clotting cases aren’t happening at a higher rate than in non-vaccinated people. There hasn’t been an increased risk of thrombotic events in the UK, where over 11 million people have already received the AstraZeneca vaccine.
But a plausible biological link between the formation of blood clots and COVID-19 vaccines might exist.
Blood clots are caused by platelets, which usually prevent us from losing too much blood when we cut ourselves. When platelets clump blood cells together unnecessarily, a blood clot forms.
Sometimes blood clots form in veins and block blood flow to parts of the body. They can also travel to vital organs such as the lungs and the brain, leading to potentially deadly consequences.
Venous thromboembolism – a clot that forms in the vein – is the third most common cardiovascular disease globally. In Australia, over 17,000 people develop venous thromboembolism every year.
What seems unusual in these European cases is that the people affected also showed platelet deficiency (thrombocytopenia), which may sound counterintuitive. “A mild reduction in platelet counts is not uncommon in people who have clots,” says Dr Phil Choi, a haematologist at Canberra Hospital and senior lecturer at the Australian National University.
We tend to think that a higher platelet count is associated with a higher tendency for clotting, says Choi, but sometimes the platelet count can be mildly reduced in patients who develop a major blood clot because platelets are consumed in the clot.
Another possible explanation is that these people might have experienced idiopathic thrombocytopenic purpura (ITP): a condition that makes the immune system produce antibodies against platelets. While the number of platelets lowers (sometimes so dangerously that it can lead to haemorrhages), this condition can also paradoxically cause blood clots.
People with ITP have a very mildly increased risk of clotting, says Choi, but that is usually due to the treatments they’re given (called prothrombotic treatments).
The question to answer is whether the AstraZeneca vaccine could have possibly elicited such a response.
“We actually have good evidence that it can because we’ve known for decades that children can get ITP after the measles vaccine,” says Choi. “People who get influenza vaccines can get ITP. But usually, these situations are very minor, and resolve on their own.”
In January, a gynaecologist in Florida, US, died due to a haemorrhage caused by a low blood platelet count after receiving the Pfizer vaccine. By February, when over 30 million people had already been vaccinated with either the Pfizer or Moderna vaccines, 36 cases of ITP were reported in the US in people who had received a COVID-19 vaccine less than two weeks earlier. It’s still unclear whether the mRNA vaccines caused the US ITP cases.
Any kind of immune-mediated process usually takes several weeks to develop, explains Choi.
“The idea that these people are getting ITP within four days of a coronavirus vaccine is very hard to believe,” he says.
It remains unknown whether COVID-19 vaccines might cause such blood conditions, but a biological link is not implausible.
How concerned should we be? Maths can help.
Even if there is a link between the vaccine and blood clotting, there’s still a very low risk associated with the AstraZeneca vaccine.
The link hasn’t been confirmed, but let’s imagine for a minute that it has. So far, 37 cases of blood clotting have been reported in Europe against 5 million people vaccinated. That’s a rate of 3.3 clots for every million vaccinations, or 0.00033%. Considering that we are vaccinating in enormous numbers, we might expect a few hundred more cases to occur, but the absolute risk remains extremely low.
Even a 20-year-old has a 1–in-16,000 chance of dying from COVID-19: 0.00625%. So if the vaccine is responsible for these blood clots, then the risk of dying from COVID-19 for a 20 year old is about 20 times higher than the risk of having a clot.
“The individual risk is tiny; compared to the hundreds of cases of mortality in Germany every day, it pales in comparison,” says Choi.
Choi suggests monitoring symptoms after receiving the AstraZeneca vaccine until more information about the European cases is released. He says that if symptoms such as headaches, feeling lethargic or unwell continue after four or five days, it’s advisable to seek medical attention.
The International Society of Thrombosis and Haemostasis has released a statement reaffirming their belief that there is no need to discontinue the AstraZeneca vaccine. So far, no reports of thrombotic events have been reported in Australia in people who have received the vaccine.