NEW WAY TO PREVENT DANGEROUS BLOOD CLOTS
For the first time,
scientists at the UNC School of Medicine have shown that eliminating the enzyme
factor XIII reduces the number of red blood cells trapped in a clot, resulting
in a 50 percent reduction in the size of the clot.
The finding, featured
in the Journal of Clinical Investigation, has major implications
for people at high risk of deep vein thrombosis (DVT), a condition that --
together with its deadly cousin pulmonary embolism -- affects 300,000 to
600,000 people in the United States every year. Between 60,000 and 100,000
people die from these conditions every year in the U.S., according to the
Centers for Disease Control and Prevention.
"If we can
develop a treatment that exploits this discovery to reduce the size of blood
clots, it would represent a whole new approach to treating thrombosis that's
different from anything else on the market," said Alisa Wolberg, PhD,
associate professor of pathology and laboratory medicine and senior author of
the JCI paper. "We think reducing factor XIII activity could be helpful to
a large number of people, perhaps including some who cannot take existing
'blood-thinning' medications."
The ability for blood
to clot is crucial to our health; by stanching bleeding long enough to allow
healing, clots keep us from bleeding to death from injuries. But in the wrong
circumstances, clots can pose a significant health hazards.
In patients with DVT,
clots that form inside blood vessels, usually in the legs, obstruct the flow of
blood, leading to pain and swelling while raising the risk of pulmonary
embolism -- a life-threatening condition in which a clot breaks away, travels
through the bloodstream, and obstructs a crucial artery in the lungs.
DVT often occurs
during periods of restricted movement, such as prolonged sitting common during
a long trip. Also, pregnancy, cancer, genetics, certain kinds of injuries,
surgeries and medications can raise the risk of developing DVT.
Many patients at high
risk for developing clots regularly take blood-thinning drugs, such as
warfarin, which stifles the body's ability to make fibrin -- the fibrous
protein that binds a clot together. But these drugs can raise the risk of
excessive bleeding, can cause side effects, and aren't appropriate for all
patients.
"What's needed is
a drug that reduces the risk of forming large clots but still allows you to
form a clot when you need one to stanch bleeding," Wolberg said. "The
biological pathway we've discovered may make it possible to strike that
balance."
In experiments using
mice and human blood, the researchers examined the role of a protein called
factor XIII in clot formation. To their surprise, they found that mice
incapable of producing factor XIII formed clots that were half the size of the
clots produced by normal mice.
"That difference
in itself was extremely striking," said Maria Aleman, PhD, first author of
the JCI paper and a graduate student in Wolberg's lab at the time of the study.
"Then, the second surprise was discovering that the size difference was
actually due to a reduced number of red blood cells in the clot. Since no
previous studies had suggested that it was possible to manipulate the number of
red blood cells, we knew we had found something new."
Factor XIII appears to
play a crucial role in helping the fibrin matrix keep its integrity during clot
formation. Normally, the fibrin matrix forms a strong mesh in and around the
clot, trapping red blood cells within. Without factor XIII, some red blood
cells are squeezed out, resulting in a much smaller clot.
Unlike existing drugs
that reduce the formation of fibrin, a drug that reduces factor XIII could
potentially cut the body's ability to produce large, dangerous clots without
sacrificing the ability to produce small, beneficial clots.
Such a drug, then,
would benefit patients at risk of developing the most dangerous kinds of clots.
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