Method of prevention of deep vein thrombosis
Dangerous thrombosis can be prevented without the risk of bleeding
Nanonews Network based on the materials of the University of North Carolina at Chapel Hill School of Medicine:
UNC researchers find new way to prevent dangerous blood clotsSuppression of the activity of blood clotting factor XIII reduces the number of red blood cells captured by the thrombus, resulting in a reduction in the size of the thrombus by 50 percent.
This was proved by scientists from the University of North Carolina School of Medicine at Chapel Hill (UNC at Chapel Hill School of Medicine).
This discovery, published in The Journal of Clinical Investigation (Aleman et al., Factor XIII activity mediates red blood cell retention in venous thrombi), is of great importance for people at high risk of developing deep vein thrombosis, which (together with pulmonary embolism) in the United States alone, 300 to 600 thousand people. According to statistics from the Centers for Disease Control and Prevention (Centers for Disease Control and Prevention), 60 to 100 thousand people die from these two diseases in the United States every year.
"If, based on this discovery, we can develop a drug that reduces the size of blood clots, it will be a completely new approach to the treatment of thrombosis, different from anything available on the market," says the head of the study, Alisa Wolberg, PhD, associate professor of the Department of Pathology and Laboratory Medicine. "We believe that suppressing the activity of factor XIII can benefit a large number of people, including, perhaps, those who cannot take existing anticoagulants."
The ability of blood to clot is crucial for our health: by stopping bleeding, blood clots save us from death. But under other circumstances, they can pose a significant danger.
In patients with deep vein thrombosis, blood clots formed in the blood vessels, usually the legs, disrupt blood circulation, which leads to pain and swelling, and increase the risk of pulmonary embolism – a life-threatening condition in which a detached blood clot blocks vital arteries in the lungs.
Many patients at high risk of blood clots regularly take blood thinning drugs such as warfarin, which inhibit the body's ability to synthesize fibrin, a fibrous protein involved in the formation of a blood clot. But these drugs increase the risk of bleeding, have side effects and are not suitable for all patients.
Venous thrombi contain a large number of red blood cells (red) and fibrin (blue) and are a kind of brickwork. Inhibition of factor XIII reduces the number of red blood cells retained in the thrombus, as a result of which its size decreases. (Photo: news.unchealthcare.org )"What is needed is a drug that reduces the risk of large blood clots, but at the same time allows the body, when necessary, to form a blood clot to stop bleeding," comments Dr. Wolberg.
"The biological pathway we have discovered may allow us to establish the right balance."
In experiments on mouse and human blood, researchers studied the role of factor XIII in the formation of a blood clot. As it turned out, mice unable to synthesize factor XIII formed blood clots twice the size of normal mice.
Left: normal blood clot. On the right: a blood clot formed in a blood sample from which factor XIII was removed. As a result of the removal of factor XIII, red blood cells fall out of the thrombus, making it twice as small. (Photo: news.unchealthcare.org )"This difference in itself was simply amazing," says Maria Aleman, PhD, PhD student of Professor Wolberg, the first author of the paper.
"But the second surprise was that the difference in size was actually explained by a decrease in the number of red blood cells in the thrombus. Since none of the previous studies suggested that it was possible to manipulate the number of red blood cells, we realized that we had found something new."
Factor XIII appears to play a crucial role in maintaining the integrity of the fibrin matrix during the formation of a blood clot. Normally, the fibrin matrix forms a strong network inside and around the thrombus, capturing red blood cells. Without factor XIII, the number of red blood cells in a blood clot decreases, resulting in a much smaller blood clot.
Unlike existing drugs that suppress the formation of fibrin, a factor XIII inhibitor drug can potentially reduce the body's ability to form large dangerous blood clots without sacrificing the ability to form small useful blood clots. Such a drug will benefit patients at risk of developing the most dangerous types of blood clots.
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