Injectable Polymer Strengthens Blood Clots to Treat Unseen, Internal Injuries

Researchers at the University of Washington (UW) have developed PolySTAT, an injectable polymer that has the ability to strengthen blood clots.

This polymer can be injected as a simple shot and it seeks internal or unseen injuries and commences working on them.

A 3-D rendering of fibrin forming a blood clot, with PolySTAT (in blue) binding strands together.William Walker/University of Washington

Most soldiers injured on the battlefield, who could possibly survive, die due to uncontrolled bleeding before they reach a hospital. Medical personnel are constrained by limited availability of resources on the battlefield.

Frozen or refrigerated blood products may not be available on the field to address blood requirements for clotting treatments. Furthermore, treatments such as the application of a tourniquet may not be sufficient for stopping bleeding from a wound in the chest.

The new PolySTAT polymer holds promise as the first line of defense for treatment in car accidents in rural areas, rescue missions to areas deep in the mountains, and on the military battlefield. Research has been conducted in rats and trials in humans may commence in around five years.

In animal trials, rats were injected with PolySTAT and others with a natural protein that had the ability to induce blood clots. All the rats administered with PolySTAT were able to survive a fatal injury to their femoral artery. However, among rats treated with the natural protein only 20% survived.

Most of the patients who die from bleeding die quickly. This is something you could potentially put in a syringe inside a backpack and give right away to reduce blood loss and keep people alive long enough to make it to medical care.

Dr. Nathan White, co-author and assistant professor of emergency medicine

Factor XIII is a natural body protein that helps strengthen blood clots. This protein had inspired the UW team.

When an injury occurs, typically, the platelets that are in the blood, assemble together at the site of the wound and begin to form an initial barrier. Fibrin, which is a network of specialized fibers, tries to reinforce the clot by weaving through it. If the pressure of the blood is greater than the strength of the scaffold, then the clot breaks, and the bleeding continues.

Factor XIII and PolySTAT strengthen clots in the same manner. They bind strands of fibrin together, and then add cross-links that support the latticework.

“It’s like the difference between twisting two ropes together and weaving a net,” said co-author Suzie Pun, the UW’s Robert J. Rushmer Professor of Bioengineering. “The cross-linked net is much stronger.”

Natural enzymes can dissolve blood clots and the synthetic PolySTAT provides better protection against these enzymes. Natural enzymes aid during healing. However, they are not favorable when patients are bleeding to death and attempts are being made to prevent the bleeding.

These enzymes have the ability to cut fibrin strands. However, they do not affect the synthetic PolySTAT bonds that are part of the clot. This feature helps in maintaining the blood clots during the crucial hours after the injury has taken place.

“We were really testing how robust the clots were that formed,” said lead author Leslie Chan, a UW doctoral student in bioengineering. “The animals injected with PolySTAT bled much less, and 100 percent of them lived.”

“The synthetic polymer offers other advantages over conventional hemorrhaging treatments”, said White, who also treats trauma patients at Harborview Medical Center.

Blood products need to be carefully stored; bacteria can grow on them, and are expensive. They may also carry infectious diseases. Furthermore, during transfusion, hundreds of proteins are sent in, which may have undesirable consequences.

When a traumatic injury occurs, a protein that is important for forming fibrin, begins to be lost by the body. When the protein levels fall below a specific threshold value, treatments that are provided may not work. This may lead to death of the patient. The researchers found that even under conditions where fibrin building blocks were very low the PolySTAT material helped to strengthen the clots.

The researchers also utilized a particular peptide that had the ability to bind to fibrin only at the wound site. Precursor of fibrins circulates in the body and this specific peptide does not bind to the precursor. Hence, the risk of formation of dangerous clots that could possibly lead to embolism or stroke is avoided when PolySTAT is used.

The team states that the initial safety profile of the polymer is promising. However, additional screening and tests on larger animals must be conducted to ascertain if PolySTAT may bind to other substances that are not desired. The researchers plan to conduct further studies to determine its potential for use in bandages and for hemophilia treatment.

Xu Wang in UW emergency medicine, Lilo Pozzo in UW chemical engineering and Hua Wei in UW bioengineering, are the other co-authors in this study.

This study on PolySTAT polymer has been featured as a cover article on Science Translational Medicine.

The National Institutes of Health, the National Center for Advancing Translational Science, Washington Research Foundation, the UW Institute of Translational Health Sciences, a UW Bioengineering Cardiovascular Training Grant supported by the NIH, and private donations have supported this study.

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