Blood clot risk much higher from COVID-19 than after vaccination: Oxford-led study

The authors noted that the risk of these adverse events is substantially higher and for a longer period of time, following infection from the SARS-CoV-2 coronavirus than after either vaccine

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The risk of developing adverse events such as blood clots is considerably higher after infection with the SARS-CoV-2 virus than after immunisation with Pfizer and AstraZeneca COVID-19 vaccines, according to a large UK study published in the British Medical Journal (BMJ) on Friday.

The team led by researchers at the University of Oxford in the UK conducted the study on thrombocytopenia -- a condition with low platelet counts -- and thromboembolic events or blood clots following COVID-19 vaccination with Oxford-AstraZeneca and Pfizer-BioNTech preventives.

Some of these events have led to restricted use of the Oxford-AstraZeneca vaccine, known as Covishield in India, in a number of countries.

The researchers compared rates of adverse events after vaccination with rates of the same events after a positive SARS-CoV-2 test result using data from over 29 million people in the UK who received the first dose of either of the two vaccines.

They concluded that with both of these vaccines, for short time intervals following the first dose, there are increased risks of some blood-related adverse events leading to hospitalisation or death.

"People should be aware of these increased risks after COVID-19 vaccination and seek medical attention promptly if they develop symptoms, but also be aware that the risks are considerably higher and over longer periods of time if they become infected with SARS-CoV-2," said Julia Hippisley-Cox, professor at the University of Oxford, and lead author of the research paper.

The authors noted that the risk of these adverse events is substantially higher and for a longer period of time, following infection from the SARS-CoV-2 coronavirus than after either vaccine.

All of the coronavirus vaccines currently in use have been tested in randomised clinical trials, which are unlikely to be large enough to detect very rare adverse events, they said.

When rare events are uncovered, then regulators perform a risk-benefit analysis of the medicine, to compare the risks of the adverse events if vaccinated versus the benefits of avoidance of the disease -- in this case, COVID-19.

The study used routinely collected electronic health records to evaluate the short-term risks (within 28 days) of hospital admission with thrombocytopenia, venous thromboembolism (VTE) and arterial thromboembolism (ATE), using data collected from across England between December 1, 2020 and April 24, 2021.

Other outcomes studied were cerebral venous sinus thrombosis (CVST), ischemic stroke, myocardial infarction and other rare arterial thrombotic events.

"This enormous study, using data on over 29 million vaccinated people, has shown that there is a very small risk of clotting and other blood disorders following first dose COVID-19 vaccination," said Aziz Sheikh, a professor at The University of Edinburgh, and a co-author of the paper.


"Though serious, the risk of these same outcomes is much higher following SARS-CoV-2 infection," Sheikh said.

The team comprised of UK-based researchers from Oxford, University of Leicester, Guys and St Thomas' NHS Foundation Trust, the Intensive Care National Audit & Research Centre, the London School of Hygiene and Tropical Medicine, the University of Cambridge, the University of Edinburgh and the University of Nottingham.

The authors pointed out some limitations to their study, including restricting the analysis to first vaccine dose only, a short vaccination exposure window, and the potential for misclassification of outcomes or exposures admissions where patients were still in hospital.

However, they believe that any bias, if present, is likely to not change with respect to each vaccine, and so the comparisons between vaccines are unlikely to be affected.

"This research is important as many other studies, while useful, have been limited by small numbers and potential biases," Hippisley-Cox said.

"Electronic healthcare records, which contain detailed recording of vaccinations, infections, outcomes and confounders, have provided us with a rich source of data with which to perform a robust evaluation of these vaccines, and compare to risks associated with COVID-19 infection," she added.

The study underscores the importance of getting vaccinated to reduce the risk of these clotting and bleeding outcomes in individuals, and because of the substantial public health benefit that COViD-19 vaccinations offer, the researchers added.

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