Researchers study link between lung cancer, thrombosis

Cancer is the second leading cause of death in the United States, but did you know that many of these deaths are because of blood clotting?

Clots form when specialized blood cells called platelets detect a tissue injury or receive a clotting signal from another cell. Platelets then become activated, releasing proteins into the blood and onto their own surface. These surface proteins act like glue, causing platelets to stick to each other and to blood vessel walls. The platelets form a plug to patch the torn blood vessel. The platelet proteins released into the blood will attract more platelets and immune cells to the injured site and help the wound to heal.

Dr. Claire Meikle is researching how platelets contribute to thrombosis in cancer patients.

Blood clotting is important to stop bleeding and heal injuries like cuts and scrapes, but sometimes clots form inside the blood vessel, blocking blood flow. When a clot forms inside a blood vessel, it prevents delivery of oxygen and nutrients to organs like the heart or brain. This kind of clot, called thrombosis, can lead to serious problems, including heart attacks and strokes.

Have you ever been warned about blood clots when you take a long airplane or car ride? Sitting still for an extended period of time allows blood to pool in your legs and reduces blood flow throughout the body. Because the blood isn’t moving, it increases risk of clots forming in the leg veins, a condition called deep vein thrombosis.

These clots are especially dangerous because they can grow to be very large and, if dislodged from the leg, they can travel through the bloodstream and get stuck in the smaller blood vessels in the lungs. This means that the blood will not be able to take fresh oxygen from the lungs to other organs and tissues in the body.

In healthy, active people risk of deep vein thrombosis is very low, and standing and walking around can be enough to prevent leg clots from forming. However, certain diseases can also make deep vein thrombosis more likely. Cancer patients are at especially high risk of thrombosis. We don’t know exactly why this is, but researchers are studying how cancer cells can make platelets more likely to form a clot. It is thought that cancer cells send pro-clotting signals to platelets, leading to a phenomenon called cancer-associated thrombosis.

Cancer patients are about five times more likely to experience thrombosis than healthy people. In fact, thrombosis occurs in as many as 20 percent of cancer patients, causing thousands of deaths each year. Chemotherapy used to treat cancer further increases the risk of thrombosis.

What can doctors do to help prevent cancer-associated thrombosis? First, clinical lab tests are used to measure a patient’s risk for clotting. In high-risk patients, drugs such as heparin can help to reduce clot formation. However, cancer patients taking these drugs are still at higher risk for clotting than people who don’t have cancer. Other health risks, including increased bleeding, are associated with taking heparin for an extended time. A better understanding of what causes clotting in cancer patients could help us develop a safer and more effective way to prevent these clots from occurring.

Platelets also help cancer cells spread to new sites in the body, a process called metastasis. Platelets do this by physically protecting cancer cells from being detected and then killed by other immune cells. Activated platelets can also release proteins that help neighboring blood vessels grow and help cancer cells survive as the cancer spreads. On top of all of this, cancer cells can trigger platelets to activate even more, increasing the risk of cancer spread and more blood clotting. This creates a vicious cycle of platelet activation and cancer spread. We don’t yet know how this cycle starts, or how to prevent it.

My research with Randall Worth at the University of Toledo College of Medicine, formerly the Medical College of Ohio, focuses on how platelets contribute to thrombosis in cancer patients, and how platelets in cancer patients differ from platelets in healthy people.

Lung cancer is the No. 1 cancer killer in the United States, and lung cancer patients are among those with the highest risk of clotting, so I am focusing on this high-risk population for my research.

I obtain blood samples from patients who have lung cancer and from healthy volunteers. I then analyze the platelets by labeling different kinds of cells with different colors, which can then be detected by a laser in a special machine. The machine will count the cells of each color. I can then compare the data across patients to look for differences.

I have found that platelets alone are not more likely to form clots in cancer patients, but they are more likely to interact with other immune cells. My next step will be to determine the mechanism of how platelets attach to immune cells. I will also explore how this attachment might affect platelet activity and the risk of thrombosis.

Further research will help us understand why lung cancer patients are more likely to develop a clot, and what we can do to prevent clots from forming. Our goal is to identify specific proteins that are involved in these cancer-specific interactions. This would allow us to develop a drug to stop only the interactions that lead to thrombosis, while allowing platelets to continue doing their usual job of healing cuts and scrapes.

Additionally, this research could help doctors understand when it could be helpful to prescribe a drug that inhibits platelet activation. We anticipate that our work will help prevent clotting in high-risk patients and, ultimately, save lives.

Claire Meikle is an M.D./PhD student in the department of medical microbiology and immunology in the University of Toledo College of Medicine and Life Sciences Biomedical Science Program. Ms. Meikle is doing her research in the laboratory of Randall Worth. For more information, contact Claire.Meikle@rockets.utoledo.edu or go to utoledo.edu/med/grad/biomedical.