PLATELET - LIKE PARTICLES AUGMENT NATURAL BLOOD BLOOD CLOTTING FOR TREATING TRAUMA
A new class of
synthetic platelet-like particles could augment natural blood clotting for the
emergency treatment of traumatic injuries -- and potentially offer doctors a
new option for curbing surgical bleeding and addressing certain blood clotting
disorders without the need for transfusions of natural platelets.
The clotting
particles, which are based on soft and deformable hydrogel materials, are
triggered by the same factor that initiates the body's own clotting processes.
Testing done in animal models and in a simulated circulatory system suggest
that the particles are effective at slowing bleeding and can safely circulate
in the bloodstream. The particles have been tested with human blood, but have
not undergone clinical trials in humans.
Supported by the
National Institutes of Health, the U.S. Department of Defense, and the American
Heart Association, the research will be reported September 7, 2014, in the
journal Nature Materials. Researchers from the Georgia Institute of
Technology, Emory University, Children's Healthcare of Atlanta and Arizona
State University collaborated on the research.
"When used by
emergency medical technicians in the civilian world or by medics in the
military, we expect this technology could reduce the number of deaths from
excessive bleeding," said Ashley Brown, a research scientist in the
Georgia Tech School of Chemistry and Biochemistry and first author of the
paper. "If EMTs and medics had particles like these that could be injected
and then go specifically to the site of a serious injury, they could help
decrease the number of deaths associated with serious injuries."
The bloodstream
contains proteins known as fibrinogen that are the precursors for fibrin, the
polymer that provides the basic structure for natural blood clots. When they
receive the right signals from a protein known as thrombin, these precursors
polymerize at the site of the bleeding. The synthetic platelet-like particles
use the same trigger, and so are activated only when the body's natural clotting
process is initiated.
To create that
trigger, the researchers followed a process known as molecular evolution to
develop an antibody that could be attached to the hydrogel particles to change
their form when they encounter thrombin-activated fibrin. The resulting
antibody has a high affinity for the polymerized form of fibrin and a low
affinity for the precursor material.
"Fibrin
production is on the back end of the clotting process, so we feel that it is a
safer place to try to interact with it," said Tom Barker, an associate
professor in the Wallace H. Coulter Department of Biomedical Engineering at
Georgia Tech and Emory University, and one of the paper's co-corresponding
authors. "The specificity of this material provides a very important advantage
in triggering clotting at just the right time."
The effectiveness of
the platelet-like particles has been tested in an animal model and in a
microfluidic chamber designed to simulate conditions within the body's
circulatory system. In the chamber, tubes about the thickness of a human hair
were lined with endothelial cells as in natural blood vessels.
The chamber was used
to study normal human blood, as well as human blood that had been depleted of
its natural platelets. In platelet-rich blood, clots formed as expected, and
blood without platelets did not form clots. When the platelet-like particles
were added to the platelet-depleted blood, it was able to clot.
The researchers also
tested blood from infants that had undergone open heart surgery, which requires
that their blood be diluted, reducing its clotting ability. When platelet-like
particles were added to the dilute neonate blood, it was able to form clots.
Finally, safety
testing was done on blood from hemophiliac patients. Because that blood lacks
the triggers needed to cause fibrin formation, the particles had no effect.
Before they can be used in humans, the particles will have to undergo human
trials and receive clearance from the U.S. Food & Drug Administration
(FDA).
About one micron in
diameter, the particles were originally developed to be used on the battlefield
by wounded soldiers, who might self-administer them using a device about the
size of a smartphone. But the researchers believe the particles could also
reduce the need for platelet transfusions in patients undergoing chemotherapy
or bypass surgery, and in those with certain blood disorders.
"For a patient
with insufficient platelets due to bleeding or an inherited disorder,
physicians often have to resort to platelet transfusions, which can be
difficult to obtain," said Dr. Wilbur Lam, another of the paper's
co-authors and a physician in the Aflac Cancer and Blood Disorders Center at
Children's Healthcare of Atlanta and the Department of Pediatrics at the Emory
University School of Medicine. "These particles could potentially be a way
to obviate the need for a transfusion. Though they don't have all the assets of
natural platelets, a number of intriguing experiments have shown that the
particles help augment the clotting process."
In addition to
providing new treatment options, the particles could also cut costs by reducing
costly natural transfusions, said Lam, who is also an assistant professor in
the Coulter Department of Biomedical Engineering at Georgia Tech and Emory
University.
What ultimately
happens to the hydrogel particles circulating in the bloodstream will be the
topic of future research, noted Brown. Particles of similar size and
composition are normally eliminated from the body.
While the
platelet-like particles lack many features of natural platelets, the
researchers were surprised to find one property in common. Clots formed by
natural platelets begin to contract over a period of hours, beginning the
body's repair process. Clots formed from the synthetic particles also contract,
but over a longer period of time, Brown noted.
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