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Synthetic Polymer Shown to Reduce Heavy Bleeding

Suzi Pun

Suzi Pun (University of Washington)

5 March 2015. A University of Washington research team developed a synthetic polymer that in lab animals acts like natural proteins to form blood clots to stop heavy bleeding, a common danger in trauma cases. The group led by Washington bioengineering faculty Suzi Pun and emergency medicine professor Nathan White published its findings yesterday in the journal Science Translational Medicine (paid subscription required).

University of Washington applied for a patent on the blood-flow controlling materials described in the research, with Pun, White, and first author Leslie Chan listed as the inventors.

The researchers were seeking a more effective way of controlling heavy bleeding often associated with traumatic injury. National Trauma Institute estimates bleeding accounts for 35 percent deaths before trauma victims reach a hospital, and 40 percent of deaths overall in the first 24 hours after the injury. The loss of blood leads to immediate complications, such as shock, and further issues including organ failure and infections. Current methods to control excessive bleeding that require infusions of purified blood and clotting factors are expensive and have a limited shelf life.

Heavy bleeding associated with trauma can exceed the body’s ability to form clots for stopping the blood flow and encourage healing. Normal blood coagulation traps platelets and other blood cells in protein fibers known as fibrin. That process is aided by an enzyme called factor XIII that strengthens and stabilizes the formation of wound-healing blood clots.

Pun, White, and colleagues designed a synthetic polymer that acts like factor XIII in the blood, and could be injected into trauma victims. The synthetic polymer that the researchers call PolySTAT combines two biocompatible and water-soluble polymers that encourage the fibrin and platelet cells to coagulate. PolySTAT also includes a peptide that makes the polymer coagulate only with fibrin, and thus discourage formation of blood clots causing strokes or embolisms.

Tests in lab simulations of fluid flow show fibrin exposed to PolySTAT form tighter coagulations than fibrin relying only on factor XIII. Further tests show fibrin enhanced with PolySTAT strengthens clots, while retaining their elasticity and resisting degradation from plasmin, an enzyme that weakens proteins in blood, including fibrin. The authors say the materials in PolySTAT are all available commercially.

The team then tested PolySTAT in lab rats with artery wounds causing severe bleeding. Rats treated with PolySTAT injections had much lower bleeding rates — as much as 11 times less — than untreated rats or those given additional factor XIII. Rats give PolySTAT also needed less fluid replacement and had longer survival times than untreated rats or those given other substances. The researchers found PolySTAT was cleared by the rats’ kidneys and livers, with no differences in functioning of these organs compared to rats who were not given PolySTAT.

The authors note that the process used to prepare PolySTAT, known as reversible addition fragmentation chain transfer or RAFT polymerization is already used in industry and offers an economic method for producing PolySTAT with production, storage, and safety advantages compared to biologic products. PolySTAT, say the authors, could also be applied to treat disorders such as factor XIII deficiency or other forms of hemophilia.

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