Nathan White – UW News /news Mon, 06 May 2019 00:58:00 +0000 en-US hourly 1 https://wordpress.org/?v=6.9.4 New method to assess platelet health could help ER doctors /news/2019/03/13/new-method-to-assess-platelet-health/ Wed, 13 Mar 2019 15:34:20 +0000 /news/?p=61175
Researchers at the ÌìÃÀÓ°ÊÓ´«Ã½ created a microfluidic device that measures platelet health in real time. Photo: Kiyomi Taguchi/ÌìÃÀÓ°ÊÓ´«Ã½

Emergency room doctors often have only a few minutes to determine which patients are in need of a blood transfusion.

But currently doctors have no direct method to assess the health of one of the most critical component of the blood: platelets. These tiny blood cells play a huge role in helping blood clot after an injury.

Now researchers at the ÌìÃÀÓ°ÊÓ´«Ã½ have created a novel system that can measure platelet function within two minutes and can help doctors determine which trauma patients might need a blood transfusion upon being admitted to a hospital. The team March 13 in Nature Communications.

“Our system requires a tiny amount of blood to look at how healthy platelets are in real time,” said co-corresponding author , an associate professor in the UW Department of Mechanical Engineering. “We found that platelet function is a far better measure of platelet health and whether a trauma patient will need a blood transfusion than current methods.”

Platelets are the first responders to any sort of damage to blood vessels.

“They act as a sort of instant patch,” Sniadecki said. “They become activated and stick to the damage, and then they rapidly change their shape to stretch and reach out for more of the wound surface or other platelets. Then they begin to come back together to compact and add strength to a clot.”

In patients who’ve experienced trauma, however, platelets can lose the ability to do their jobs, including becoming less able to apply the forces needed to stop bleeding.

“When trauma patients come into the ER, we use a variety of methods to estimate their risk of bleeding, but none of these tests tells us specifically about platelet strength,” said co-corresponding author , an associate professor of emergency medicine at the UW School of Medicine.

White, Sniadecki and their team designed a microfluidic device that measures platelet forces in real time. First, the researchers inject a blood sample into the device. As the blood flows through it, the cells hit an obstacle course: tiny blocks and posts jutting up from the base of the device. This activates the platelets. They feel a massive force when they flow over the blocks, and then the surface of both the blocks and the posts are coated with a platelet-activating molecule.

The team designed a microfluidic device that measures platelet forces in real time. As the blood flows through it, the cells hit an obstacle course: tiny blocks and posts jutting up from the base of the device. This activates the platelets. Photo: ÌìÃÀÓ°ÊÓ´«Ã½

“The block and post structures act like a mini wound surface,” said lead author , who conducted this research as a mechanical engineering doctoral student at the UW. “The platelets attach between the block and post, and they start to snowball. They aggregate to form a miniature plug that then begins to contract and pull the post toward the block. Based on how far the post moves, we can determine how functional the platelets are.”

Tiny blocks and posts in the microfluidic device activate platelets and measure their health. This image was taken on a scanning electron microscope, and the block is 15 microns tall, or about one-tenth the thickness of a piece of paper. Photo: ÌìÃÀÓ°ÊÓ´«Ã½

Sniadecki’s lab has used to measure cell forces, but this is the first time that blocks have been added to the mix. Without the blocks, the platelets didn’t stick to the posts.

“As the platelets whip around the block, they are forced to change direction rapidly, and that activates the platelets,” Ting said.

To test their device, the researchers recruited participants from Harborview Medical Center. After providing informed consent, 93 trauma patients and 10 healthy participants had their blood sampled when they arrived at the center.

The results showed a significant difference between the healthy participants’ blood and that of the trauma patients. Trauma patients’ platelets had decreased forces compared to healthy participants’ platelets. Of the trauma patients, 17 required a blood transfusion during their first 24 hours in the hospital. These patients also had the lowest platelet forces compared to the trauma patients who didn’t receive a transfusion.

Sometimes trauma patients have fewer platelets, so one current test in the ER is to count the number of platelets. But when the researchers looked at platelet count for this study, all blood samples — including those from healthy participants — had a comparable number of platelets.

“It’s a big deal not just knowing how many platelets are in the blood but knowing how well they’re actually functioning,” White said. “It’s not always obvious which patients will need a blood transfusion, and a device like this can really help us make decisions quickly.”

Healthy platelets (false colored blue here) attach between the block and post, and then they begin to pull the post toward the block. Healthier platelets pull the post back farther compared to platelets that have experienced trauma. This image was taken on a scanning electron microscope. Photo: ÌìÃÀÓ°ÊÓ´«Ã½

Currently the team is working to make the device more user-friendly.

“It’s still a prototype where you have to have some training in how to operate it to get a reading,” said Ting, who is now director of research and development at , the company that spun out from this research. “Our goal is to make it user-friendly and comparable to a blood sugar monitoring device where people deposit blood samples on a strip and put it into the reader. Then the reader just takes care of it.”

The team also hopes the device will be useful for measuring platelet strength in other areas of medicine, such as measuring how blood-thinning medications like aspirin or Plavix affect different patients or helping neurosurgeons monitor patients for bleeding complications during surgery.

Co-authors include , a senior engineer at BD Biosciences who conducted this research while a UW mechanical engineering doctoral student; , a mechanical engineering doctoral student; Annie Smith, who was a mechanical engineering research scientist but is now a research scientist at Stasys; , the director of operations at Stasys who completed this work as a mechanical engineering postdoctoral fellow; , a scientist at the Seattle Cancer Care Alliance who conducted this research as a research scientist at UW Medicine; , an assistant professor of emergency medicine at Harborview Medical Center; Xu Wang, a UW emergency medicine research scientist; and , a biostatistics research scientist. The microfluidics cards used in this study were made at the  at UW.

This research was funded by the Defense Advanced Research Projects Agency Young Faculty Award, the Coulter Foundation Translational Research Award, grants from the Life Science Discovery Fund, the Combined Funding Initiative, ÌìÃÀÓ°ÊÓ´«Ã½ CoMotion, the National Science Foundation and the National Institutes of Health.

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For more information, contact Sniadecki at nsniadec@uw.edu.

Grant numbers: N66001-11-1-4129, LSDF-7434512, CMMI-1402673, UL1TR000423, KL2TR000421, EB001650

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An injectable UW polymer could keep soldiers, trauma patients from bleeding to death /news/2015/03/10/an-injectable-uw-polymer-could-keep-soldiers-trauma-patients-from-bleeding-to-death/ Tue, 10 Mar 2015 16:53:55 +0000 /news/?p=35890 Most military battlefield casualties die before ever reaching a surgical hospital. Of those soldiers who might potentially survive, .

A 3-D rendering of fibrin forming a blood clot, with PolySTAT (in blue) binding strands together. Photo: William Walker/ÌìÃÀÓ°ÊÓ´«Ã½

In some cases, there’s not much medics can do — a tourniquet won’t stop bleeding from a chest wound, and clotting treatments that require refrigerated or frozen blood products aren’t always available in the field.

That’s why ÌìÃÀÓ°ÊÓ´«Ã½ researchers have developed a new injectable polymer that strengthens blood clots, called PolySTAT. Administered in a simple shot, the polymer finds any unseen or internal injuries and starts working immediately.

The new polymer, described featured on the cover of the March 4 issue of could become a first line of defense in everything from battlefield injuries to rural car accidents to search and rescue missions deep in the mountains. It has been tested in rats, and researchers say it could reach human trials in five years.

In the initial study with rats, 100 percent of animals injected with PolySTAT survived a typically-lethal injury to the femoral artery. Only 20 percent of rats treated with a natural protein that helps blood clot survived.

All rats injected with PolySTAT survived potentially lethal bleeding from femoral artery injury. In control groups, zero to 40 percent of rats survived. Photo: ÌìÃÀÓ°ÊÓ´«Ã½

“Most of the patients who die from bleeding die quickly,” said co-author , an assistant professor of who teamed with UW and to develop the macromolecule.

“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,” he said.

The UW team was inspired by , a natural protein found in the body that helps strengthen blood clots.

Normally after an injury, platelets in the blood begin to congregate at the wound and form an initial barrier. Then a network of specialized fibers — — start weaving themselves throughout the clot to reinforce it.

If that scaffolding can’t withstand the pressure of blood pushing against it, the clot breaks apart and the patient keeps bleeding.

Both PolySTAT and factor XIII strengthen clots by binding fibrin strands together and adding “cross-links” that reinforce the latticework of that natural bandage.

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

But the synthetic PolySTAT offers greater protection against natural enzymes that dissolve blood clots. Those help during the healing process, but they work against doctors trying to keep patients from bleeding to death.

The enzymes, which cut fibrin strands, don’t target the synthetic PolySTAT bonds that are now integrated into the clot. That helps keep the blood clots intact in the critical hours after an injury.

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

Blood clots treated with PolySTAT (second from right) had denser fibrin networks, which helps reinforce and strengthen the clots. Photo: ÌìÃÀÓ°ÊÓ´«Ã½

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

Blood products are expensive, need careful storage, and they can grow bacteria or carry infectious diseases, he said. Plus, the hundreds of proteins introduced into a patient’s body during a transfusion can have unintended consequences.

After a traumatic injury, the body also begins to lose a protein that’s critical to forming fibrin. Once those levels drop below a certain threshold, existing treatments stop working and patients are more likely to die.

In the study, researchers found PolySTAT worked to strengthen clots even in cases where those fibrin building blocks were critically low.

The UW team also used a highly specific peptide that only binds to fibrin at the wound site. It does not bind to a precursor of fibrin that circulates throughout the body. That means PolySTAT shouldn’t form dangerous clots that can lead to a stroke or embolism.

Though the polymer’s initial safety profile looks promising, researchers said, next steps include testing on larger animals and additional screening to find out if it binds to any other unintended substances. They also plan to investigate its potential for treating hemophilia and for integration into bandages.

Other co-authors are Xu Wang in UW emergency medicine, Hua Wei in UW bioengineering, and in UW chemical engineering.

Funding came from the National Institutes of Health and its National Center for Advancing Translational Science, the UW , the Washington Research Foundation, an NIH-supported UW Bioengineering Cardiovascular Training Grant and discretionary funds from private donations.

For more information, contact Pun at spun@uw.edu or White at whiten4@uw.edu.

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Engineering lecture series focuses on technologies for the heart /news/2014/10/10/engineering-lecture-series-focuses-on-technologies-for-the-heart/ Fri, 10 Oct 2014 15:23:45 +0000 /news/?p=34001 The heart often goes unnoticed until something goes wrong.2014 flyer image

During the next month, the ÌìÃÀÓ°ÊÓ´«Ã½’s College of Engineering will feature faculty researchers in engineering and medicine who are improving cardiac medical care with new technologies. All lectures are free and open to the public.

The series kicks off on Wednesday (Oct. 15) in 120 Kane Hall with “.” , a UW professor of pathology, cardiology and bioengineering, will share how his team is using engineering, stem cells and medicine to regenerate heart muscle. This could help rebuild muscle tissue after a heart attack.

On Tuesday, Nov. 4, in 120 Kane Hall, speakers will talk about the biomechanics of cells in the cardiovascular system. We depend on active cells that can create blood clots to prevent blood loss in an injury or pump blood throughout our bodies when we exercise. UW engineers and physicians are studying cell biomechanics to try to improve blood clotting to help with healing in traumatic injuries.

, an associate professor of mechanical engineering and adjunct professor of bioengineering, and , an assistant professor of emergency medicine and adjunct assistant professor of bioengineering, will present “.”

Finally, on Tuesday, Nov. 18, the focus will be on new ways to power implantable devices such as pacemakers. Using battery packs and even cables to run these electronics is cumbersome, and engineers are discovering ways to wirelessly deliver power to devices by harvesting ambient cellular phone and TV signals from the air. , an associate professor of computer science and engineering and of electrical engineering, will explain his team’s work in this field in “.”

All lectures are free and start at 7 p.m. Advance registration, either or by calling 206-543-0540, is required. All lectures will be broadcast at a later date on .

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