New study of 46 million adults in England confirms blood clot risk with COVID-19 vaccine is very small

A new study confirms that the risk of blood clots after COVID-19 vaccinations is very low. It showed that people vaccinated with Oxford-AstraZeneca or Pfizer-BioNTech had a lower risk of all venous clots (such as deep vein thrombosis and pulmonary embolism) and all arterial clots (such as strokes and heart attacks), particularly in people over 70 years. The research team, which included Jonathan Sterne, Director of the NIHR Bristol Biomedical Research Centre (BRC) found that 1–3 extra people per million had an intracranial venous thrombosis after the Oxford-AstraZeneca vaccine, but that there was no evidence that these rare blood clots were associated with the Pfizer-BioNTech vaccine.

The study results have been released this week in PLoS Medicine. Led by the CVD-COVID-UK consortium and the Longitudinal Health and Wellbeing COVID-19 National Core Study, this study measured the associations of COVID-19 vaccines with blood clots in the whole adult population of England.

Researchers analysed linked NHS England data from over 46 million adults in England, from the beginning of the COVID-19 vaccination programme on 8 December 2020 until 18 March 2021. Researchers looked for episodes of blood clots in the arteries or veins, and of low levels of platelets (blood cells that help with clotting) in adults before COVID-19 vaccination, after COVID-19 vaccination and in those not vaccinated at all. The research team used NHS Digital’s Trusted Research Environment (TRE) Service for England, which ensures that that data is secure. To protect privacy, all identifiers (such as names, addresses and NHS numbers) were removed and results could not be exported from the TRE until they were confirmed not to include information that could identify individual patients.

The NHS health data analysed includes information from GPs, hospitals, death certificates and COVID-19 testing and vaccination data. Researchers considered separately those under the age of 70 years and those aged 70 years and over, and those who received a first vaccine of either the Oxford-AstraZeneca or Pfizer-BioNTech vaccine (other vaccines were not included in the study).

Importantly, this study minimised the chance that something other than the vaccine could be causing associations of vaccines with blood clots, by taking into account a comprehensive range of other factors known to impact on the incidence of clotting events. These included age, sex, ethnicity, deprivation level, previous medical history and medications.

The research was conducted by members of the CVD-COVID-UK consortium, a National Institute for Health Research (NIHR) and British Heart Foundation (BHF) flagship project led by the BHF Data Science Centre at Health Data Research UK. The CVD-COVID-UK consortium is a collaborative group of more than 260 members across over 50 institutions across the UK, working together with patient and public contributors to understand the relationship between COVID-19 and cardiovascular diseases such as heart attack and stroke in the UK population. The research was also conducted by researchers from the Longitudinal Health and Wellbeing COVID-19 National Core Study, which aims to understand the health, social and economic impacts of the COVID-19 pandemic by uniting established population cohorts and national anonymised electronic health records to inform policy.

This collaborative study was carried out with support from the British Heart Foundation, the Stroke Association, and the Data and Connectivity COVID-19 National Core Study. Members of the research team are based at the Universities of Edinburgh, Bristol, Cambridge, Swansea, University College London, the BHF Data Science Centre and NHS Digital.

Dr William Whiteley, project lead at the University of Edinburgh, said:

“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. 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.”

Prof Cathie Sudlow, Director of the BHF Data Science Centre said:

“This study illustrates the importance of linking and analysing data from several different healthcare settings for a very large population. Including data from 46 million adults meant that we could pick up very rare clotting events, while linking data across different healthcare settings in the safe setting of the NHS Digital Trusted Research Environment meant we could take into account a very broad range of factors apart from vaccination that affect the risk of blood clots. The BHF Data Science Centre is delighted to have been able to support this collaborative, team science effort involving members of the public as well as researchers from many UK institutions.”

Prof Jonathan Sterne from the University of Bristol, who is co-lead of the Longitudinal Health and Wellbeing COVID-19 National Core Study, said

“The COVID-19 vaccines have been crucial to the UK and international response to the pandemic, but like all vaccines they have rare side effects. I hope that, by putting the small risk of serious harms in the context of the huge benefits of vaccination, our work can help reassure people who are concerned about these side effects.”

Dr Richard Francis, Head of Research at the Stroke Association said:

“We are relieved to see that this research has shown that COVID-19 vaccines are unlikely to cause stroke except in fewer than 1-3 people in a million. Unfortunately, we already know that catching the virus without being vaccinated significantly increases your risk of a stroke. This research will help people to understand how their overall risk of stroke is affected by getting vaccinated. We look forward to the findings of research into why catching the virus increases your risk of stroke and how to prevent this.”

This work will enable better understanding of the balance between the very small but serious harms versus the substantial known benefits of COVID-19 vaccines. Updates on this work have been provided to the Department of Health, Medicines and Healthcare products Regulatory Agency (MHRA), and the Joint Committee on Vaccination and Immunisation (JCVI), to inform current health guidance and policies.

The research team will continue to address additional questions, including: establishing more precise estimates of vaccine-associated risks in young adults; studying other COVID-19 vaccines; assessing the effects of receiving a second dose of vaccine; understanding how COVID-19 infection can affect risk of blood clots; and examining the impact of vaccines beyond 28 days after vaccination.

 

Paper: Association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous,
arterial, or thrombocytopenic events: A population-based cohort study of 46 million
adults in England  William Whiteley et al., PLOS Medicine