Target inflammation to better understand dangerous blood clots

It's the third most deadly cardiovascular diagnosis, but doctors are still often perplexed as to why 40% of patients suffer from unprovoked venous thromboembolism (VTE). And once the patient has dealt with these dangerous blood clots, a second event and subsequent events become much more likely.

New research conducted by a team of scientists from the University of Michigan could help solve the mystery of detecting and managing a risk of upper-normal coagulation in patients' veins. The study, conducted in mice and published in the Journal of Clinical Investigation, focuses on the relationship between clots and the body's defense and repair system, which causes inflammation.

"We do not yet understand the molecular triggers that regulate the development of life-threatening clots in deep veins," said Yogen Kanthi, MD, lead author of the study and Vascular Cardiologist at Frankel's Cardiovascular Center. 39; UM. "Our work was aimed at identifying and blocking a previously unrecognized pathway linking inflammation and thrombosis."

Kanthi, also an badistant professor of internal medicine at Michigan Medicine, explains that VTE is caused by a combination of coagulation and inflammation. But current treatments are inadequate, he says, because they only focus on one side of the equation: anticoagulation. After VTE, patients are often prescribed anticoagulants for life.

Kanthi's laboratory is studying rather the role of inflammation in the development of deep vein thrombosis. His team's new study found an enzyme called CD39 that delivers circulating "danger" signals and inflammatory cytokines in the blood during thrombosis.

FDA-approved drugs already exist for other conditions affected by the same pathway, and particularly for the paradigmatic molecule of inflammatory cytokine called interleukin-1 beta. In fact, when researchers inhibited interleukin-1 signals in their study, they reduced the number and size of venous blood clots formed by animals, Kanthi said.

"Here we focused on potential therapeutics at the intersection of inflammation and thrombosis," Kanthi said. "We have shown that blocking interleukin 1 beta, an ubiquitous inflammatory molecule, was a powerful way to stop clot formation."

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Earlier this year, Kanthi and his colleagues published an article in Arteriosclerosis, thrombosis and vascular biology CD39 as important for venous thrombo-inflammatory response.

For updates on this research and other research done at Kanthi Lab, follow Kanthi on Twitter @YogenKanthi.

Other authors, all from the University of Michigan, include co-first authors, Vinita Yadav and Liguo Chi, Raymond Zhao, Benjamin Tourdot, Srilakshmi Yalavarthi, Benjamin N. Jacobs, Alison Banka, Hui Liao, Sharon Koonse, Anuli C. Anyanwu and Scott. Visovatti, Michael Holinstat, J. Michelle Kahlenberg, Jason S. Knight and David J. Pinsky.

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