There is a slightly elevated risk of intracranial thrombosis events following vaccination with the AstraZeneca ChAdOx1-S COVID-19 vaccine, according to two new studies publishing in PLOS Medicine.[1] Combined, these papers included more than 30 million U.K. patients.
Despite the elevated risk, the teams behind these studies said the benefits of the vaccine far outweigh any potential risks.
Cases of thromboses have been reported after vaccination with the Astra Zeneca ChAdOx1-S COVID-19 vaccine, but the rates of common venous and arterial events, including stroke, myocardial infarction, deep vein thrombosis and pulmonary embolism, are hard to measure based on a small number of case reports alone.
In the first study, William Whiteley, MSc, PhD, MRCP, of the University of Edinburgh in the United Kingdom, and colleagues from the BHF Data Science Centre analyzed the EHR data of 46 million adults living in England. A total of 21 million patients were vaccinated from December 2020 to March 2021. For people aged 70 or over, the risks of arterial and venous thrombotic events were slightly lower in the 28 days following vaccination with either the Pfizer BNT162b2 or ChAdOx1-S vaccine after adjusting for a range of demographic characteristics and comorbidities. In people under age 70, the risks of arterial and venous thrombotic events were comparable in the 28 days following vaccination, but a small increase in the rate of intracranial venous thrombosis (ICVT) was observed following vaccination with the ChAdOx1-S vaccine.
This corresponded to an estimated excess risk of 0.9 – 3 per million, varying by age and sex. This was about twice the rate compared to unvaccinated people, after adjusting for a range of demographic characteristics and comorbidities. The same effect was not seen after the BNT162b2 (Pfizer BioNTech) vaccine.
“In adults under 70 years, the small increased risks of intracranial venous thrombosis and hospitalization with thrombocytopenia after first vaccination with ChAdOx1-S are likely to be outweighed by the vaccines’ effect in reducing COVID-19 mortality and morbidity,” the authors wrote.
“Because of its very large size, this research study has provided precise results on the risks of rare blood clotting events and of low platelet levels following COVID-19 vaccination," Whiteley said in a statement. "We were able to show that these risks occur only in people under 70 years old with the Oxford-AstraZeneca vaccine and that the increase in risk is extremely small—no more than a few people per million vaccinated.”
For the second analysis, Steven Kerr, also of the University of Edinburgh, and colleagues, used a dataset of 11 million adults in England, Scotland and Wales. This included data spanning December 2020 through June 2021 from multiple sources—including primary care, secondary care, mortality and virological testing. They compared the rate of cerebral venous sinus thrombosis (CVST) events—a rare type of blood clot in the brain—in the 90 days prior to vaccination and the four weeks following a first dose of ChAdOx1-S or BNT162b2. The authors observed a small elevated risk of CVST events following vaccination with ChAdOx1-S, equivalent to one additional event per 4 million people vaccinated, which was approximately twice as high as before vaccination. The study found no association between the BNT162b2 vaccine and CVST.
“This evidence may be useful in risk-benefit evaluations for vaccine-related policies, and in providing quantification of risks associated with vaccination to the general public,” the authors wrote.
The teams behind both studies cautioned that the low number of overall events of CVST and other subtypes of thromboses, even in large cohorts, makes precise estimates of the risks difficult. They plan to carry out future studies to include other vaccines as well as second and booster vaccinations.
“In this analysis using data from England, Scotland and Wales, we found a roughly two-fold increased risk of a rare form of blood clot in the brain following the Oxford-AstraZeneca vaccine, but we did not see any increased risk for the Pfizer vaccine," Kerr added. "We used a novel method that allowed us to do the analysis across several countries without them having to share person-level data with each other, and we hope to take advantage of this in future to allow greater collaboration across the U.K.”
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Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: dfornell@innovatehealthcare.com