Studying the link between COVID-19 vaccines and rare blood clots

Deep vein thrombosis - blood disorder abstract.

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A new, rapid nationwide study aiming to understand the vascular complications around blood clots after coronavirus vaccination is now underway.

New research has now begun following reports of a very rare condition involving blood clots and low platelet levels after COVID-19 vaccinations. The research is led by the British Heart Foundation (BHF) Data Science Centre – a partnership between UKRI-funded Health Data Research UK (HDR UK) and the BHF.

The rapid study will access healthcare records of all people in England. Firstly to identify who’s had a disease involving blood clots in the arteries or veins, and who’s been diagnosed with low platelet levels.

The study will then compare the risk of developing one of these conditions among people who have had a COVID-19 vaccine versus those who have not had a vaccine.

Statistical accuracy

With more than 30 million people vaccinated in the UK so far, the primary aim of the vaccine-blood-clotting research is to provide rapid, precise results regarding the vaccine and rare side-effects. And that means initially using data on England’s population.

Professor Cathie Sudlow, Director of the BHF Data Science Centre explained:

A very large population is really important for looking at these rare events.

We knew colleagues were working in Scotland and Wales on similar initiatives, but because of the much smaller size of the populations they’re studying, they might not pick up enough of the very rare events for a robust analysis.

Yet, with the English population, we have 56 million people in the linkage dataset that we’re working with. A linkage dataset is what we create when we bring information from different health sources together about the same people to create a new, richer dataset.

The very large size of the dataset gives us substantial statistical power when it comes to studying rare events and looking at COVID-19 vaccine benefits versus risks. This enables us to provide robust results in as short a time as we can without duplicating efforts.

Rapid response

Professor Sudlow and her team have been able to respond rapidly to the emergence of the rare COVID vaccine side effects. This has been possible due to research they are already carrying out via the BHF Data Science Centre’s CVD (Cardiovascular)-COVID-UK project.

This is one of the National Institute for Health Research-BHF flagship projects, and aims to understand the relationship between COVID-19 and cardiovascular diseases such as heart attack, heart failure, stroke, and blood clots in the lungs. They do this through analyses of linked, nationally-collated healthcare datasets across the four nations of the UK.

The project runs in NHS Digital’s Trusted Research Environment (TRE) which ensures that data is secure. It ensures that all direct identifiers (such as names, addresses and NHS numbers) are removed so that people’s privacy is protected. Furthermore, only summary research results – and not data on individual people – can be taken out of the environment for wider sharing.

Through the Medical Research Council, the Engineering and Physical Sciences Research Council and Economic and Social Research Council, UKRI was a core funder of HDR UK, which was established in 2017. This was in recognition of the pivotal role health data plays in achieving healthcare transformation.

Pivoted rapidly

Professor Sudlow said:

With Dr William Whiteley of University of Edinburgh leading, we had a project already running that was looking at clotting events in the context of COVID-19, so we rapidly extended that project to look at clotting events in the context of the COVID-19 vaccine.

The same team who’d been working on that existing project then pivoted rapidly to start thinking about the vaccine.

It’s a big task. We need to turn this around as quickly as we can to inform the Department of Health, the Medicines and Healthcare Regulatory Agency and the Joint Committee on Vaccines and Immunisation so that everyone relevant is informed.

NHS Digital

Scotland and Wales already had nationally collated health records, Wales via Secure Anonymised Information Linkage and Scotland via the Scottish National Data Safe Haven. Before 2020 there was not a trusted research environment to make England’s national health records securely available for research.

To address this, NHS Digital was tasked with building and then launching a new TRE for England. With HDR UK’s Professor Sudlow and her team at the heart of the programme, to ensure it properly delivered the service researchers needed.

Major step forward

Professor Sudlow explained:

Before the COVID-19 pandemic, we didn’t have, in England, a trusted research environment where data could be held with secure, efficient access to approved researchers.

We have been working with NHS Digital to create their first trusted research environment to hold almost the entire population of England’s data, linking across different health data sources in a trusted, secure, data-safe environment.

The data sources we are using include GP data, which covers 98% of practices, as well as data from the hospitals, and death certificates.

The very fact that NHS Digital now has this secure environment where they link the data and make it available securely, that’s completely new and it’s really a major step forward.

All data that could identify individual people (like names, addresses, exact dates of birth) are removed from the data accessed by researchers and replaced by a dummy ID, which means that no individual can be identified by researchers working with the data.

It’s allowed regulatory bodies to feel comfortable providing permissions for access. They can make a lot more data available because they can keep an eye on what’s going on under the safe umbrella of an extremely data-secure environment.

Next steps

Professor Sudlow expects initial results of the rapid vaccine-related research to be available in the coming weeks. Yet it’s just the beginning. Due to the evolving nature of COVID-19, the work will continue.

Professor Sudlow said:

It’s a very dynamic environment and it’s constantly moving.

We’re currently in the process of expanding our approvals so that we can broaden the uses of the data for wider public benefit. Any UK-based bona fide researcher can join our consortium and seek approval to run analyses.

We are now pretty much set up to start generating initial results, but we’ll need to keep revisiting them because the vaccine rollout is not yet complete.

Next, we intend to expand to working with all UK data sets in collaboration with others, as well as looking to share results internationally.

Blood clot statistics

COVID-19 vaccine

Overview: Although blood clots linked to the COVID vaccine remain extremely rare there appears to be a higher risk in people shortly after the first dose of the AstraZeneca (AZ) vaccine.

Risk rate: So far, we know that around 10 people develop this condition for every million doses of AZ vaccine doses given. That’s 0.000001%.

Find out more at: COVID-19 vaccination and blood clotting (GOV.UK).

The combined oral contraceptive pill

Overview: The combined oral contraceptive pill contains artificial versions of female hormones oestrogen and progesterone. The oestrogen in the pill may, in rare cases, cause blood to clot more readily.

Risk rate: The estimated incidence of a blood clot with the combined oral contraceptive pill is about five per 10,000 women per year – a risk of one in 2,000, or 0.05 per cent.

Find out more at: Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis (The BMJ).

Long-haul flights

Overview: Deep vein thrombosis is a blood clotting condition that affects veins deep inside the body and can, in rare cases, occur after a long-haul flight of more than four hours.

Risk rate: The annual incidence of deep vein thrombosis (DVT) in the general population is estimated to be about one in 1,000 or 0.001%. The risk of developing DVT rises two-three fold after long-haul flights (more than four hours).

Find out more at: Risks of developing travel-related DVT (National Institute for Health and Care Excellence).

Surgery

Overview: The level of risk for postoperative thrombosis (blood clots) depends on the type of surgery and coexisting risk factors. Postoperative deep vein thrombosis and pulmonary embolism are the most prevailing thrombotic complications.

Risk rate: The frequency of deep vein thrombosis after general surgical procedures is approximately 20 to 25%, with nearly 2% of these patients displaying clinically significant pulmonary embolism.

Find out more at: Postoperative thrombosis (ScienceDirect).

CVD-COVID-UK consortium

The CVD-COVID-UK consortium (HDR UK) is a collaborative group of more than 160 members across 41 institutions working to understand the relationship between COVID-19 and cardiovascular diseases. The consortium is managed by the BHF Data Science Centre, led by HDR UK.

Last updated: 20 May 2021

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