The University of Oxford-AstraZeneca coronavirus vaccine triggers a potentially "devastating" blood clot in just one in 50,000 people aged under 50, research has shown.
The jab was approved after a study demonstrated it is up to 90% effective at warding off COVID-19, the disease caused by the infection.
Although safe in the vast majority of cases, the Oxford-AstraZeneca vaccine has been linked to an unusual form of blood clots, defined by a low number of clotting cells called platelets.
With the clots somewhat of a mystery, a team of scientists analysed the UK's first 220 cases of what they have called vaccine-induced immune thrombocytopenia and thrombosis (VITT) – a clot with a low number of platelets that blocks a blood vessel.
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Off the back of these cases, the scientists have developed a case definition criteria for VITT, allowing medics to identify and treat patients earlier in their illness' onset.
To mitigate the risk, people under 40 in England have routinely been offered an alternate coronavirus vaccine since early May, 2021. Younger people are less likely to develop COVID-19 itself, skewing the risk-benefit ratio when it comes to receiving the Oxford-AstraZeneca jab.
After analysing the 220 cases, the scientists found just under a quarter (23%) of the patients who presented to hospital with definite or probable VITT later died of the condition.
The mortality rate increased to nearly three quarters (73%) among the patients with a particularly low platelet count and bleeding within the brain as a result of a clot.
"It's important to stress this kind of reaction to the Oxford-AstraZeneca vaccine is very rare," said lead scientist Dr Sue Pavord, from the Oxford University Hospitals NHS Foundation Trust.
"In those aged under 50, incidence is around one in 50,000 people who have received the vaccine, but our study shows that for those who develop VITT, it can be devastating.
"It often affects young, otherwise healthy vaccine recipients and has high mortality.
"It is particularly dangerous when the patient has a low platelet count and bleeding in the brain."
Writing in the New England Journal of Medicine, the scientists outline how the first of five VITT criteria is a patient arriving at hospital five to 30 days after receiving the Oxford-AstraZeneca vaccine.
"Before that it's not VITT related," said Dr Pavord. "It takes five days for this immune response to develop."
The other criteria include a low platelet count and a known clot that is blocking a blood vessel.
Another tell-tale sign is having "very raised" levels of D-dimers, protein fragments that are produced when a clot is broken down.
Finally, the scientists look for the presence of infection-fighting proteins called antibodies against so-called platelet factor 4. This creates complexes that activate cells that cause clots.
"VITT is a very new syndrome and we are still working out what the most effective treatment is, but identifying prognostic markers has helped to determine what is the more effective way to manage the condition," said Dr Pavord.
"For example, we have adapted our treatments for patients with the most severe disease, to include plasma exchange with some success." Plasma exchange involves removing the liquid part of a patient's blood and replacing it with that of a healthy volunteer.
More than four in five (85%) of the 220 patients were under 60. This is despite older people being more at risk of coronavirus complications and getting vaccinated earlier in the immunisation programme.
VITT's prevalence does not differ between males and females, according to the analysis. Unlike COVID-19 itself, the risk of VITT is also not higher among those with pre-existing medical conditions.
"It can affect anybody," said Professor Beverley Hunt, from King's College London. "There is no predisposing factor we can identify.
"About 50% of the patients we saw had no previous medical illness."
While it may sound alarming, the scientists have stressed people should get vaccinated when called up, with the coronavirus itself posing a greater clot risk.
"We have worked relentlessly to understand and manage this new condition, so the hugely successful vaccine roll out can continue, which is the most viable solution to the global pandemic," said Dr Pavord, who met with the team of scientists every day of the analysis.
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