A gunshot wound or any traumatic injury resulting in massive blood loss leaves victims with about a 50% chance of survival.
Two things are crucial for survival: a large infusion of blood and the ability for the blood to clot and stop the bleeding. Unfortunately, one of these solutions often interferes with the other.
When a large amount of blood is introduced into the body, it hampers the blood’s ability to clot, a condition known as coagulopathy.
Researchers from Tulane University have made significant progress in understanding the cause of coagulopathy in trauma victims undergoing massive blood infusions.
They have also found that a synthetic compound called dimethyl malonate, typically used in perfume production, can potentially prevent coagulopathy during massive hemorrhage.
These findings were published in a recent study in Science Advances.
Prior studies have suggested that coagulopathy is caused by the shedding of the glycocalyx, a protective sugar layer around cells.
In blood vessels, the glycocalyx prevents blood from clotting. However, the exact events leading to the disintegration of the glycocalyx were unknown until now.
The Tulane researchers discovered that during blood loss, cells lack the oxygen necessary to metabolize succinate, a critical element of the cell’s energy cycle.
As a result, succinate builds up. When a large amount of blood is then infused into the trauma victim, the succinate is metabolized too quickly.
This rapid metabolism alters the structure of the plasma membrane lipids, exposes the glycocalyx, allows it to be broken down by enzymes, and mixes the remnants into the bloodstream, inhibiting clotting.
In animal models, dimethyl malonate was able to inhibit excessive cellular metabolism, thereby preventing the shedding of the glycocalyx and the subsequent coagulopathy.
This finding has the potential to revolutionize trauma care.
“We were getting 60% mortality with our animal model. With dimethyl malonate, we got zero percent mortality, and the coagulopathy completely went away,” said Olan Jackson-Weaver, Ph.D., assistant professor of surgery at Tulane University School of Medicine.
While these results are promising, further research is needed to determine whether dimethyl malonate is safe for human use or if an equivalent drug targeting cellular metabolism can be developed.
“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,” added Jackson-Weaver.
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The study was published in Science Advances.
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