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Second-dose Oxford-AstraZeneca and Pfizer-BioNTech vaccines and blood clotting and bleeding events in Scotland

August 2022: Research published in Nature Communications looks at potential side effects of second dose COVID-19 vaccines, related to bleeding and blood clotting.

Info-graphic showing highlights from this research paper. Read the article below to find out more.
This image was created by the Usher Institute, The University of Edinburgh to accompany a research study by the EAVE II team funded by the Medical Research Council [MR/R008345/1] and the Data and Connectivity National Core Study [MC_PC_20058], and supported by BREATHE - The Health Data Research Hub for Respiratory Health [MC_PC_19004]. © 2022 Usher Institute, The University of Edinburgh. All rights reserved.

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

Simpson, C.R; Kerr, S.; Katikireddi, S.V; McGowan, C.; et.al

Published in Nature Communications

Published online on: 15 August 2022

Available online at: https://doi.org/10.1038/s41467-022-32264-6

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This infographic was created by the EAVE II's Communications & Engagement Officer, Gabriella Linning (Usher Institute, The University of Edinburgh)

Plain English Summary

The three COVID-19 vaccines currently available in the UK have been shown to reduce infections, hospital admissions and deaths related to the disease. They are:

  • Pfizer-BioNTech (BNT162b2 mRNA) – introduced in UK on 8 December 2020;
  • Oxford-AstraZeneca (ChAdOx1 nCoV-19) – introduced in UK on 4 January 2021;
  • Moderna (mRNA-1273) – introduced in UK on 7 April 2021.

Vaccines can have side effects, also known as adverse events. Most, like headaches and soreness at the injection site, are common and mild. Other events are very rare, and may need treatment.

There have been some rare reports of people having side effects related to bleeding or blood clotting, after having a COVID-19 vaccine.

Why did we carry out this research?

In previous research using data from the Scottish population, we studied possible links between some of these side effects and having a first dose of the Oxford-AstraZeneca or Pfizer-BioNTech vaccine.

View the summary of previous research in this area

We wanted to provide evidence on the safety of second doses of these two common vaccines. We monitored bleeding or blood clotting-related side effects reported to have links with COVID-19 vaccination. Ongoing vaccine monitoring in national populations helps to pick up rare side effects, which might not be seen in clinical trials.

What data did we use?

To look at side effects, we used data from 3.8 million people in the Scottish population who had a second vaccine dose between 11 January and 7 November 2021.

We included people aged 16+ who had the Pfizer-BioNTech or Oxford-AstraZeneca vaccine. We did not include the Moderna vaccine in our study, as too few people had the vaccine to carry out reliable analysis.

We compared each person in the dataset before and after their second vaccine. We monitored the data for 0-27 days after a person’s second dose to look for vaccine-related side effects.

The analysis contains data collected from 1 December 2020 to 7 November 2021. This data is part of the EAVE II dataset. We used information on people’s vaccine status; RT-PCR (‘reverse transcriptase polymerase chain reaction’) tests for COVID-19; clinical records including relevant blood tests; and death records.

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What did we find?

Over three quarters (78.2%) of people eligible for vaccines had a second dose in the time period studied.

We studied the following conditions. Arteries and veins are types of blood vessel.

  • Thrombocytopenia: a low platelet count in the blood. Platelets form clots when blood vessels are damaged, preventing blood loss.
  • Idiopathic thrombocytopenic purpura (ITP): a form of thrombocytopenia where the body’s immune system attacks platelets, causing a low platelet count.
  • ‘Venous thromboembolic events’: blood clots that form in the veins and/or break away from the clotting site, travelling through the veins.
  • Cerebral venous sinus thrombosis (CVST): a rare form of stroke, caused by a blood clot on the brain.
  • Deep vein thrombosis (DVT): A blood clot in a vein deep in the body, usually in the leg.
  • Pulmonary embolism (PE): A blockage of an artery in the lung.
  • ‘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. 
  • ‘Hemorrhagic events’: blood loss. This can be internal or external bleeding.

Vaccine second doses

Of all the conditions studied, we found two which showed a borderline increased risk after the second dose of an Oxford-AstraZeneca vaccine. These are ‘idiopathic thrombocytopenic purpura’ (ITP) and ‘cerebral venous sinus thrombosis’ (CVST). A borderline result means that there may be a link, but the results are not precise enough to be certain.

We did not find any link between the conditions studied and having a second dose of the Pfizer-BioNTech vaccine.

People requiring medical treatment

In our study, five of the thirteen people (39%) with ITP had to go to hospital, with a typical stay of 1-2 days before being discharged. When compared to unvaccinated people, vaccinated people with ITP were more likely to have other medication which could cause the condition.

Fewer than five people experienced CVST in the 0-27 days after their second vaccine. These people required hospital treatment, with a typical stay of 8 days before being discharged. The CVST patients were all female and had an average age of 62. There were no patient deaths from any of the conditions studied.

Why is this research important?

This is one of the first studies in the world to look at side effects in all people who had a second dose of a common COVID-19 vaccine in a national population. We looked at eight side effects related to bleeding and blood clotting.

We have shown that there is a borderline increased risk of CVST and ITP after the second dose of an Oxford-AstraZeneca vaccine. These side effects are extremely rare and treatable. We did not find links between any of the remaining conditions and this vaccine. There was no association between Pfizer-BioNTech second doses and the conditions studied. We were not able to study the Moderna vaccine.

This type of research can be used to update vaccine safety information booklets. It can also help patients and healthcare professionals make shared, evidence-based decisions about the relative benefits of getting a vaccine. This is especially important if they are at particular risk of these side effects.


This plain English summary was created with the support and feedback of the EAVE II Public Advisory Group (PAG). This particular plain English summary was reviewed by PAG members Eve S and Farzana K.