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Understanding Blood Clot Lysis, or How Clots Break Down

March 16, 2022

Ze Zheng, MBBS, PhD, studies how blood clots break down in patients with heart conditions and bleeding and clotting diseases.


Adverse blood clots affect millions of people each year, with hundreds of thousands dying annually. People with obesity, diabetes and dyslipidemia might have reduced capacity to break down blood clots, adding potential risk of developing cardiovascular diseases and adverse blood clots. In her research laboratory at Versiti Blood Research Institute, Assistant Investigator Ze Zheng, MBBS, PhD, studies fibrinolysis, the process of how blood clots break down. “It’s an area of research that requires better understanding and treatment in order to help patients who experience adverse clotting,” she said.

Deficient breakdown of blood clots in cardiovascular diseases

For every process of a clot forming, there is also a system by which it breaks down. An imbalance between the formation and breakdown of blood clots can leads to pathological consequences. “That can be in people who have a pathological blood clot, including diseases like heart attack, stroke or pulmonary embolism,” she said, or in patients with bleeding disorders like hemophilia. Dr. Zheng studies both, with a goal of better understanding these processes in both subsets of patients and how to manage them.

“One of the key points in my lab’s research is how we link high lipids in populations with higher risks of developing blood clots, including obesity and fatty liver diseases,” she said. The liver is responsible for producing the factors in blood that break down blood clots. When the liver becomes afflicted by obesity or fatty liver conditions, its ability to naturally break down blood clots is lower.

To better understand this process, Dr. Zheng studies a protein called tissue plasminogen activator (tPA), an essential component in the breakdown of blood clots. “There is lots of room to improve if we understand the biology of tPA clearly,” Dr. Zheng said, and why the breakdown of blood clots is lower in patients who are obese.

Accelerated blood clot lysis in patients with bleeding disorders

In addition to her research of how to improve outcomes for people at higher risk for clotting, Dr. Zheng studies how to help blood to clot in patients with bleeding disorders. “The way that hemophilia severity is diagnosed isn’t necessarily on the bleeding, but rather the factor activity,” she said. The lower a person’s clotting factor (a protein in blood), the more severe their disorder. However, the variation of bleeding severity is also associated with other factors, including the blood clot breakdown system. The higher the clot lysis, the worse bleeding that has been observed in hemophilia patients.

“Our goal is to understand the role of tPA in hemophilia patients, especially those with severe bleeding,” Dr. Zheng said. She hopes that this research will help the scientific community to understand if higher tPA could contribute to more severe bleeding disorder types. “We’re doing research to carefully look into the activity for blood clot lysis and compare that with bleeding severity in severe hemophilia patients,” she said. “We want to see if there is any way to decrease their bleeding risk by lowering the blood clot lysis system.”

Connecting COVID-19 and blood clots

In addition to her study of clot lysis in high-risk patients and those with bleeding disorders, Dr. Zheng studies how clots form in patients with COVID-19 with a goal of better understanding the defects in the clot breakdown system. She was recently awarded a grant with Investigator Renren Wen, PhD, and Medical Director of Hematology Lisa Baumann Kreuziger, MD, MS, to conduct several studies of patients hospitalized for COVID-19. They found that the blood clot lysis capacity was lower in hospitalized patients with COVID-19 but increased after recovery from COVID-19 symptoms.

Making strides at VBRI

Dr. Zheng joined VBRI after completing her postdoctoral training at Columbia University in New York City. She hopes to serve as an advocate for early career development, including students and research fellows. “At VBRI, we’re not just doing research,” she said. “We’re also mentoring the next generation of scientists, who will establish new avenues of research.”

About the expert: Ze Zheng, MBBS, PhD, is an assistant investigator at Versiti Blood Research Institute and an assistant professor of medicine in the Division of Endocrinology and Molecular Medicine, the Department of Medicine, and the Department of Physiology at the Medical College of Wisconsin.

Versiti Blood Research Institute Articles
Research articles that explore Versiti Blood Research Institute investigators and their expertise in blood health innovation.
Lisa Baumann Kreuziger, MD, MS
Dr. Baumann Kreuziger is a medical director of hematology and investigator at Versiti Blood Research Institute who specializes in non-malignant hematology.
Renren Wen, PhD
Dr. Wen is an investigator at Versiti Blood Research Institute who studies immune cell activation and the interaction between the immune and coagulation systems.
Ze Zheng, MBBS, PhD
Dr. Zheng is an associate investigator at Versiti Blood Research Institute who studies the interaction between metabolism and clot lysis.