New tech aims to tackle 'disseminated intravascular coagulation' blood disorder

February 17, 2021

Researchers have developed a new tool for addressing disseminated intravascular coagulation (DIC) - a blood disorder that proves fatal in many patients. The technology has not yet entered clinical trials, but in vivo studies using rat models and in vitro models using blood from DIC patients highlight the tech's potential.

"DIC basically causes too much clotting and too much bleeding at the same time," says Ashley Brown, corresponding author of a paper on the work. "Small blood clots can form throughout the circulatory system, often causing organ damage. And because this taxes the body's supply of clotting factors, patients also experience excess bleeding. Depending on the severity of DIC, between 40% and 78% of patients with DIC die.

"DIC is associated with a number of other conditions, such as sepsis and cancer - and it is very difficult to treat," adds Brown, who is an assistant professor in the Joint Department of Biomedical Engineering at North Carolina State University and the University of North Carolina at Chapel Hill. "Doctors often focus on trying to treat underlying condition. But if the DIC is bad, doctors face a dilemma: if they treat the bleeding, they'll make the clotting worse; if they treat the clotting, they'll make the bleeding worse. Our goal is to find a clinical intervention that addresses this dilemma. And our results so far are promising."

Brown and her collaborators have developed a technique that makes use of nanogel spheres. The spheres are engineered to bind to a protein called fibrin, which is the main protein found in blood clots. As a result, the spheres will travel through the bloodstream until they reach a blood clot, at which point they will stick to the fibrin in the clot.

These nanospheres are about 250 nanometers in diameter and are porous. In this case, the researchers have loaded the nanospheres with tissue-type plasminogen activator (tPA) - a drug that breaks down clots.

"Based on in vitro testing and testing in a rat model, we found that where you have pre-formed clots (not active bleeding) that the tPA spheres stick to fibrin and break up the clots," says Emily Mihalko, first author of the paper and a Ph.D. candidate in the joint biomedical engineering department. "Breaking up these clots also releases other clot constituents, such as platelets, which evidence suggests may be re-recruited by the body at active clotting sites (i.e., places where there was actually bleeding)."

In one study, the researchers evaluated the use of the tPA and targeted nanospheres in a rat model involving DIC that stems from sepsis. In that study, the researchers found that delivering tPA via the targeted nanospheres eliminated 91 and 93% of the clots found in the heart and lung respectively, and 77% of the clots found in the liver and kidneys.

"We also did in vitro testing using blood plasma from patients with DIC, and found similarly promising results," Brown says.

"We are currently exploring different dosages in the animal model," Mihalko says. "And are doing work to better understand how the particles are distributed in the body and how long it takes before they are cleared by the body - which is important information for addressing safety considerations prior to any clinical trials."

The researchers note that it is too early to put a price tag on any potential treatments that make use of the technology. However, they note that the targeted nanogels mean that treatment would likely involve using smaller doses of tPA than are currently in clinical use.

"The cost of the creating the targeted nanospheres would likely offset the savings from using less tPA, so we suspect it may be comparable to the cost of conventional tPA therapies," Brown says.
The paper, "Fibrin-modulating nanogels for treatment of disseminated intravascular coagulation," appears in the journal Blood Advances. The paper was co-authored by Megan Sandry, a former undergraduate in the joint department of biomedical engineering; Nicholas Mininni, an undergraduate in the joint department; Kimberly Nellenbach and Halston Deal, Ph.D. students in the joint department; Michael Daniele, an associate professor of electrical and computer engineering at NC State; Kamrouz Ghadimi, an associate professor of anesthesiology and critical care at Duke University; and Jerrold Levy, professor of anesthesiology and critical care at Duke University.

The work was done with support from the National Science Foundation, under grant 1847488; the National Heart, Lung, and Blood Institute, under grant R01HL146701; a Flash grant from the North Carolina Biotechnology Center; an American Heart Association Predoctoral Fellowship; funding from the U.S. Department of Defense under grant CDMRP W81XWH-15-1-0485; and the National Institute of General Medical Sciences, under grant T32 GM008600.

Brown is the founder of SelSym Biotech, Inc., which focuses on developing injectable hemostatic materials. Levy serves on advisory boards for Instrumentation Labs, Octapharma and Merck.

North Carolina State University

Related Blood Clots Articles from Brightsurf:

New cause of COVID-19 blood clots identified
A new study reveals that COVID-19 triggers production of antibodies circulating through the blood, causing clots in people hospitalized with the disease.

Children who take steroids at increased risk for diabetes, high blood pressure, blood clots
Children who take oral steroids to treat asthma or autoimmune diseases have an increased risk of diabetes, high blood pressure, and blood clots, according to Rutgers researchers.

COVID-19 may cause deadly blood clots
COVID-19 may increase the risk of blot cots in women who are pregnant or taking estrogen with birth control or hormone replacement therapy, according to a new manuscript published in the Endocrine Society's journal, Endocrinology.

New evidence for how blood clots may form in very ill COVID-19 patients
Neutrophil Extracellular Traps (NETs) have been implicated in causing excessive clotting in cancer patients.

Researchers find new way to detect blood clots
Researchers in the Department of Biomedical Engineering at Texas A&M University are working on an entirely new way to detect blood clots, especially in pediatric patients.

High rate of blood clots in COVID-19
COVID-19 is associated with a high incidence of venous thromboembolism, blood clots in the venous circulation, according to a study conducted by researchers at Brighton and Sussex Medical School (BSMS), UK.

New tool helps distinguish the cause of blood clots
A new tool using cutting-edge technology is able to distinguish different types of blood clots based on what caused them, according to a study published today in eLife.

Hookah smoke may be associated with increased risk of blood clots
In a new study conducted in mice, researchers found that tobacco smoke from a hookah caused blood to function abnormally and be more likely to clot and quickly form blood clots.

Reducing the risk of blood clots in artificial heart valves
People with mechanical heart valves need blood thinners on a daily basis, because they have a higher risk of blood clots and stroke.

New study provides insight into the mechanisms of blood clots in cancer patients
Researchers have identified a potential new signaling pathway that may help further the understanding of blood clot formation in cancer patients and ultimately help prevent this complication from occurring.

Read More: Blood Clots News and Blood Clots Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to