The compound called dimethyl malonate prevents a condition that stops blood from coagulating when trauma casualties are given a transfusion, according to a new research published in Journal Science Advances.
Doctors say the chances of surviving massive blood loss from a traumatic injury such as a gunshot wound are around 50 percent.
To survive, a patient needs two things to happen quickly: a large infusion of blood and coagulation at the wound to stop the bleeding.
But the problem is one of those solutions prevents the other. Introducing a large amount of blood to those suffering a massive hemorrhage impairs the blood’s ability to clot, a condition known as coagulopathy.
Now, American scientists have found the cause of coagulopathy in trauma victims receiving a blood infusion.
They also discovered that a synthetic compound called dimethyl malonate – often used in the manufacture of perfume – has the potential to stop coagulopathy during a massive hemorrhage.
Study corresponding author Dr. Olan Jackson-Weaver said: “Coagulopathy of trauma is a major contributor to mortality, but no treatment has shown to be fully effective.
“We were getting 60 per cent mortality with our animal model. With dimethyl malonate, we got zero per cent mortality, and the coagulopathy completely went away.”
Due to gun violence, trauma is a leading cause of death in the United States, especially for children and young adults.
Recent studies have shown that coagulopathy during massive hemorrhage treatment is most likely caused by the shedding of the glycocalyx, a barrier of sugars that surrounds and protects cells.
The research team explained that, in blood vessels, the glycocalyx lines the vessel walls and prevents blood from clotting.
However, the new research is the first to identify the cellular events that cause the glycocalyx to be ripped apart.
The new study found that, during blood loss, a person’s cells lack the oxygen to metabolize succinate, a key part of the cell’s energy-generating cycle. Unable to be metabolized, the succinate builds up.
When a large amount of blood is infused into a trauma victim – the succinate is metabolized too quickly, which leads to a change in the structure of the plasma membrane lipids.
That exposes the glycocalyx, allows it to be chewed up by enzymes, and mixes the shreds into the bloodstream, where it prevents clotting.
Dr. Jackson-Weaver, an assistant professor of surgery at Tulane University School of Medicine, said: “People have been trying to figure out ways to move the needle a little bit on the death rate from massive hemorrhage for the last 20 or so years and nothing has really worked.
“We’re hopeful that understanding these cellular-level events can help to develop something that actually does make a big difference.”
In animal models, dimethyl malonate was effective at inhibiting excessive cellular metabolism, which prevented the glycocalyx from shedding and causing coagulopathy.
But Dr. Jackson-Weaver said more research is needed to determine whether dimethyl malonate is safe for humans or if an equivalent drug that targets cellular metabolism can be developed.
He added: “We’ve established this pathway that causes coagulopathy, so if we can target it therapeutically with a pre-hospital drug or injection, we can hopefully save some lives.”
Edited by Deborah .C. Amirize and Alberto Arellano
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