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First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland.

EAVE II study of 2.53 million first COVID-19 vaccine doses across Scotland shows small increases in risk for some adverse events following Oxford-AstraZeneca vaccine.

First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland.

Simpson, C.R., Shi, T., Vasileiou, E. et al.

Available via Nature Medicine: https://doi.org/10.1038/s41591-021-01408-4 

This careful analysis of an entire country’s vaccination programme, which involved the study of over 2.5m first dose vaccines, has found a small increase in the risk of ITP, clotting and bleeding events following the Oxford-AstraZeneca vaccine. This very small risk is important, but needs to be seen within the context of the very clear benefits of the vaccines and potentially higher risks of these outcomes in those who develop COVID-19.

Professor Aziz SheikhDirector of the University of Edinburgh’s Usher Institute and EAVE II Study Lead

Plain English summary

Are first doses of COVID-19 vaccines linked to adverse events? The study looked at: 2.53 million first dose vaccinations in Scotland, between 8th December 2020 and 14th April 2021. 1.71 million: Oxford-AstraZeneca 0.82 million: Pfizer-BioNTech Results: Small increases in risk for some adverse events, seen only in Oxford-AstraZeneca. Pfizer-BioNTech first dose: No link to increased risk of any of the adverse events studied. Oxford-AstraZeneca first dose: No increase in risk of venous thromboembolic events (blood clots formed in the veins). Small increase in risk of ITP (low platelet count in the blood). Equivalent to 113 cases for every 10 million doses. Suggested increase in risk of arterial thromboembolic (blood clots formed in the arteries) and haemorrhagic events (blood loss). All adverse events studied are very rare and less than those associated with COVID-19.
Infographic highlighting key findings from the paper.

The Pfizer-BioNTech (BNT162b2 mRNA) and Oxford-AstraZeneca (ChAdOx1 nCoV-19) vaccines have been tested in clinical trials and found to be safe and effective for use. In other research, we have shown the high effectiveness of the first doses of these vaccines in preventing hospital admission across the Scottish population.

Common side effects from the vaccines, known as adverse events, include:

  • soreness at the injection site
  • headaches
  • joint and muscle pain
  • nausea and fever.

Reports of serious adverse events have been rare.

Why did we carry out this study?

By 21 April 2021, the body that regulates medicines and healthcare products in the UK had received reports of 209 people experiencing adverse events in their blood after having the Oxford-AstraZeneca vaccine. By this time, 22 million first doses and 6.8 million second doses of the vaccine had been safely given in the UK.

On the basis of these reports and similar data across Europe, several countries decided to stop or restrict use of the Oxford-AstraZeneca vaccine. After this, some countries only allowed its use in people above a certain age. The age limit varies from country to country and is set at 40 in the UK.

We wanted to investigate the possible link between COVID-19 vaccines and low platelet count, blood clotting or bleeding events, to provide urgently needed information on vaccine safety at a national scale.

Our research focused on people who received their first dose of either the Oxford-AstraZeneca or Pfizer-BioNTech vaccine in Scotland between 8 December 2020 and 14 April 2021.

The study included 57.5% of the Scottish population, or 2.53 million people. Of these:

  • 1.71 million people had the Oxford-AstraZeneca vaccine
  • 0.82 million people had the Pfizer-BioNTech vaccine
  • Less than 10,000 people had the Moderna (mRNA 1273) vaccine  

We did not investigate the Moderna vaccine because the vaccinated population is too small to study rare events.

What adverse events were being studied?

We included four main types of adverse events in the study, based on patient reports. These are:

  • Idiopathic thrombocytopenic purpura (ITP) – a low platelet count in the blood. Platelets form clots when blood vessels are damaged, preventing blood loss.
  • Venous thromboembolic events – blood clots that form in the veins and/or break away from the clotting site, travelling through the veins.
  • Arterial thromboembolic events – blood clots that form in the arteries and/or break away from the clotting site. In serious cases, this can result in heart attack or stroke.
  • Haemorrhagic events – blood loss. This can be internal or external bleeding.

What methods were used in this study?

The study used two main methods to look at the data. These are known as an incident matched case control study and a self-controlled case series (SCCS) analysis.

In the incident matched case control study, every person found to have low platelet count or a blood clotting or bleeding event, after the first dose of a vaccine was paired with similar people who had not been affected. This method is used to check for any other possible causes of the adverse event.

Only people with no history of these events since 1 September 2019 were included as cases in the study. The matching was based on age by year, sex at birth, health history and residential area.

We checked all positive findings from the matched case control study using the SCCS method. This method calculates the risk of an adverse event for each affected person before and after vaccination, rather than comparing them to others.

What can we conclude from this study?

The study found that the Pfizer-BioNTech vaccine first dose has no link with increased risk of any of the adverse events listed above.

The first dose of the Oxford-AstraZeneca vaccine was linked to a small increased risk of ITP (low platelet count), equivalent to 113 cases for every 10 million doses. No increased risk was found for venous thromboembolic events after having the Oxford-AstraZeneca vaccine.

We found a suggestion of increased risk of arterial thromboembolic and haemorrhage events with the Oxford-AstraZeneca vaccine.

All of these events are very rare. The risk of them happening after vaccination is at a similar level to other common vaccines, including Hepatitis B, MMR, and Influenza.

Why is this research important?

This is one of the first real-world studies of rare low platelet count, blood clotting and bleeding events of all vaccinated people at a national level. Large studies like this are needed to identify rare adverse events and show whether they are likely to be linked to the vaccine. The data can be used to ensure safety in national vaccination programmes, especially ones that have prioritised by COVID-19 risk level.

What is next?

In this research, we looked at low platelet, blood clotting and bleeding events after the first dose of the two most commonly available vaccines in the UK. Because older and at-risk groups were prioritised for vaccines, there were less data for younger vaccinated people and those not thought to be at high risk of serious COVID-19 outcomes.

We plan to update our health data analysis as the vaccine programme continues. This will include younger groups, second doses, and newly approved vaccines like Moderna and Janssen.

Cite as

Simpson, C.R., Shi, T., Vasileiou, E. et al. First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland. Nat Med (2021). https://doi.org/10.1038/s41591-021-01408-4

Note

This plain English summary and infographic were created with the support and feedback of the EAVE II Patient Advisory Group (PAG). To learn more about the PAG, see Our EAVE II Patient Advisory Group (PAG) | The University of Edinburgh