“Don’t poke the bear”, they said. But that’s exactly what our team of scientists has been doing, to discover the secrets of blood clotting. Hibernating bears, paralysed humans, and pigs kept in small enclosures all avoid dangerous blood clots, despite being immobile for extremely long periods.

Deep vein thrombosis is a life-threatening condition that occurs when a blood clot develops within a vein, usually within the leg, and it is commonly triggered by immobilisation.

If you’ve ever taken a long haul flight, you might have taken advice to prevent deep vein thrombosis from forming in one or both of your legs, while you sit still for multiple hours, dreaming of your destination. Perhaps you set a reminder to get up and walk around, and you wore compression socks to keep the blood from pooling in your legs.

Most people won’t experience a clot if they take care on a flight, but there is a serious risk for some people who are pre-disposed to blood clots, due to genetic factors.

In the UK, one in 1000 people are affected by deep vein thrombosis each year, leading to painful and swollen legs. If left untreated, one in 10 cases can result in a pulmonary embolism, a condition in which this dangerous blood clot travels through the circulatory system to the lungs, leading to breathlessness and chest pain. Both of these medical conditions require urgent attention.

Curiously, long-term immobility such as patients with a spinal cord injury or hibernating animals, does not trigger deep vein thrombosis. The reason for this was not understood.

Our team of scientists worked with partners in Denmark, Germany, Norway and Sweden to collect blood samples from bears in winter, while hibernating, and in summer, while awake and moving around.

We discovered that a protein called HSP47, which is released by platelets – the sticky blood cells that trigger blood clotting, was dramatically reduced in samples taken from the bears during hibernation.

We used a number of other immobility models in this work, including comparing humans with spinal cord injury to matched controls and a study in which mobile humans underwent voluntary bed rest for a prolonged period of time. Again, samples taken from patients during immobility showed a significant reduction in platelet HSP47 which suggests their bodies were toning down the production of this protein in response to being immobilised.

Clotting is an important response to an injury, to prevent blood loss, and HSP47 is one of the necessary ingredients to enable platelets to do their job. When examining the role of HSP47 in clotting function we found that when released into the blood of bears, mice and humans it promoted conditions that may give rise to deep vein thrombosis.

This suggested HSP47’s importance within the circulatory system as a mechanism that plays a key role in preventing clots, not just in humans, but in other mammals.

Identification of this previously unknown mechanism in the body that protects against deep vein thrombosis may lead to new drugs, new treatment options, and improved diagnostic tests to help those who have inherited blood clotting disorders that put them at risk for pulmonary embolism, heart attack, and stroke.

The initial studies that identified HSP47 on the surface of platelets were carried out at the University of Reading.  Work has since gone on to understand the role of HSP47 in resting and stimulated platelets, and in 2018, we showed that HSP47 on platelets increases clot formation and helps to maintain haemostasis. Further work in 2023 identified the mechanisms in which HSP47 functions within the platelet leading to a greater understanding of this protein and its role within the circulatory system.

Gemma Little is a Research Assistant in Biomedical Sciences at the University of Reading and winner of the University’s 2024 Research Output Prize (Agriculture, Food & Health theme) for her paper as co-author published in Science: ‘Immobility-associated thrombo-protection is conserved across mammalian species from bear to human’.