Investigating the Immune System’s Connection to Blood Clots

Serious infections increase the risk of life-threatening conditions such as deep vein thrombosis (DVT), a blood clot that can form in deep veins, and pulmonary embolisms (PE), a condition where an artery in the lung becomes blocked by a blood clot. These conditions affect 1 in 1000 adults and lead to approximately 200,000-300,000 deaths per year.

In an effort to better understand blood clots, Andrea Obi, M.D., a vascular surgeon and investigator at Michigan Medicine's Frankel Cardiovascular Center, is exploring the condition further through new research in her lab.

Her team is establishing a link between infection, thrombosis and changes in the bone marrow programming of immune cells and working on understanding the interplay between the immune system and thrombosis to help identify new, non-blood thinning techniques for preventing and treating DVT in the future.

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Obi, also the winner of the 2019 Wylie award from Vascular Cures, takes a deeper dive into her work here with questions from the Michigan Health Lab:

What's the focus of your research?

My research focuses on the intersection between innate immunity and the coagulation system, specifically evaluating the role immune cells play in forming and breaking down blood clots in the venous system.

What sparked your interest in this?

My current work, like many surgeons, was the result of observing human suffering. During the 2009-2010 H1N1 influenza outbreak, I spent much time in the surgical intensive care unit caring for young individuals, some in their 20s and 30s, with severe pulmonary disease requiring advanced life support. We noticed that a large number of these patients developed severe venous clotting, leading to a very high mortality. Blood thinners helped us decrease the risk of death but led to a host of other bleeding complications for these ill patients.

When I had a chance to review data from large population studies, it became evident that DVT was associated with all types of infections to varying degrees, and the risk persisted over the course of the person's next year of life, even if he or she made a rapid recovery.

What discoveries has your team already made?

So far we've discovered that even with a remote infection, such as a pneumonia, the endothelium (inner lining of the blood vessel) in a remote location changes the proteins expressed on the cell surface and "talks" to circulating leukocytes differently.

How will patients benefit from this research?

My hope is that by using both animal models and human tissue we can identify some of the changes that occur in innate immune cell memory that predisposes individuals to form a DVT after suffering from an infection.

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In recent years, the pharmacology for a wide range of diseases such as rheumatoid arthritis, psoriasis, and melanoma have been transformed by the ability to target the immune system. Despite the fact that it's never been tried in DVT, doesn't mean that it is impossible, rather that we just don't understand enough about the crosstalk between the immune system and coagulation (blood clotting) system to identify a protein or molecule that we can manipulate to change the course of human disease.

I hope that in the course of my work and in my lifetime we can make a discovery that decreases the need for dangerous blood thinning medication and improves the lives of individuals who are at high risk or whom have suffered from a DVT.

Read more from Dr. Obi about her research goals and progress in this blog post from the Michigan Medicine Department of Surgery.