Procoagulant phospholipids in arterial thrombosis
Research type
Research Study
Full title
A pilot, exploratory study to investigate procoagulant phospholipids in arterial thrombosis
IRAS ID
243701
Contact name
Majd Protty
Contact email
Sponsor organisation
Cardiff and Vale University Health Board
Duration of Study in the UK
3 years, 3 months, 0 days
Research summary
Research Summary:
Cardiovascular (heart) disease is the number one cause of death in the UK. Patients with heart disease who experience a heart attack are at a higher risk of suffering another heart attack, stroke or death. Heart attacks happen as a result of blockages in heart arteries. These blockages are caused by inflammation (a reaction to a damaging irritant) and lead to activation of blood cells such as white cells (responsible for wound healing) and platelets (responsible for blood clotting) which in turn lead to abnormal clotting and blockages in arteries.
Blood clotting happens through interactions of blood proteins with particular fats (phospholipids) that are present on the surface of blood cells and are linked to inflammation. Their potential role in driving abnormal clotting events in heart attacks is unknown. If identified, it may serve as a potential new treatment. This is important since one in ten patients who experience a heart attack remain at risk of developing another heart attack, or a stroke, despite current treatment.
Here, I will characterize the phospholipid profile generated by blood cells and components in patients with heart disease, with the aim of identifying the drivers of clotting in these patients, and new treatment targets.
Summary of results:
People with atherosclerotic cardiovascular disease (ASCVD) have changes in how certain blood cells - like platelets and white blood cells - make substances that help the blood clot. These changes may increase the risk of dangerous blood clots forming.
Aspirin is the most commonly used medicine around the world to prevent further heart attacks or strokes. It works mainly by blocking a chemical in platelets that helps them stick together. In general, aspirin is used to prevent clots in arteries, while drugs like warfarin are more often used for clots in veins.
This study found that aspirin - but not other similar drugs called P2Y12 inhibitors - affects the way these clot-promoting substances are made, both in healthy people and in those with ASCVD. This suggests aspirin may have extra effects on clotting that we need to understand better.
The researchers also identified a protein called LPCAT3, which helps control how these clotting substances are produced. Since aspirin influences LPCAT3, this could be a new target for future treatments aimed at reducing clot risk.
In addition, we also found that tiny particles in the blood called extracellular vesicles (EVs) play a key role in clot formation in ASCVD. These EVs provide a surface that helps generate thrombin - a major clotting factor - in the blood. While platelets didn’t seem to be the main source of this effect, white blood cells may be involved. Stopping EVs from forming, or from interacting with clotting proteins, could be a new way to reduce the risk of blood clots in people with ASCVD.
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REC name
Yorkshire & The Humber - Leeds East Research Ethics Committee
REC reference
18/YH/0502
Date of REC Opinion
17 Jan 2019
REC opinion
Further Information Favourable Opinion