New hope to prevent blood clots in legs
Common anti-allergy medicines could prove to be an effective treatment for potentially fatal blood clots in the legs, according to new research by the University of Birmingham
The research, funded by the British Heart Foundation, could lead to new treatments that prevent deep vein thrombosis (DVT) – a health issue that can be a particular problem on long-haul flights or other situations related to long-term immobilization.
The team from the University of Birmingham has discovered that mice genetically depleted of mast cells, a type of immune cells, are protected from developing DVT.
DVT is a blood clot that develops within a deep vein in the body, usually in the leg, and causes swelling, aching and difficulty walking. It can be caused by prolonged periods of immobility, such as after surgery or during a long flight. If the clot becomes dislodged it can travel to the lungs and block a blood vessel – this is known as a pulmonary embolism (PE). An estimated thirty per cent of PEs cause sudden death.
The current treatments for DVT, which affects around 60,000 people in the UK every year, include anti-clotting drugs such as heparin and warfarin. These drugs are relatively effective but put patients at increased risk of bleeding. This is because as well as targeting the blood clot, they also affect haemostasis, the body's natural response to blood vessel injury and bleeding. Imbalanced haemostasis can be dangerous, so patients have to be monitored carefully and hospitalised following bleeding injury.
In the study, published in Circulation Research, the researchers ‘turned off’ the gene that is responsible for producing mast cells. The research found that the mice which were deficient in mast cells were protected from DVT. They also found that mast-cell deficient mice had normal haemostasis, tackling the bleeding side-effects possible with treatments such as warfarin.
Now, the researchers are hoping to validate their findings in humans, by testing samples of blood from people with and without DVT, to see if people with DVT have activated mast cells. If positive, mast cell inhibitors, which are already approved for treatment of some allergic diseases such as asthma, could quickly move into human clinical trials.
Dr Alex Brill, of the Institute of Cardiovascular Sciences at the University of Birmingham, said: “These findings offer new hope for the treatment of deep vein thrombosis without a risk of bleeding. If further human studies support our findings in mice, drugs to block mast cell production could be used in the future alongside lower doses of anticoagulants such as warfarin, significantly reducing bleeding risk.
“This is particularly exciting because this is a group of drugs which already exists, and some forms are approved for the treatment of allergies such as hay fever and asthma, meaning that this discovery could help people with DVT sooner rather than later.”
Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, said: “Those setting off on long haul flights this summer should be aware of the risk of DVT, which can be triggered by immobility. However there are ways to reduce your risk, such as walking around the aeroplane or wearing anti-DVT socks. This is even more important for people already at risk of DVT, who carry other risk factors such as old age, obesity, smoking, and being pregnant.
“It’s far too soon to suggest people should start taking anti-allergy tablets to prevent DVT but this exciting discovery may pave the way for new treatments, and reduce some of the bleeding side effects which come with anticoagulants such as warfarin. However further research is needed to show that the same protective effect can be seen in humans.”
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Notes to editors
- Ponomaryov et al (2017). ‘Mast Cells Granular Contents Are Crucial for Deep Vein Thrombosis in Mice’. Circulation Research. DOI: 10.1161/CIRCRESAHA.117.311185
- Read the full paper.
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