Clots and Cancer Carry Hidden Double Risk

Rochester Researchers Study Trends and Blood Clot Prevention

August 02, 2007

Blood clots are increasingly common in cancer patients, but University of Rochester Medical Center researchers have created a novel risk model that can predict, with 98 percent certainty, which patients will not get a blood clot.

The goal is to improve patient care by preventing early deaths due to blood clots -- a complication that struck 41,666 of 1 million hospitalized cancer patients between 1995 and 2003, according Rochester researchers. That was higher than the rates reported from two earlier time periods.

One reason for the jump in cancer-related clots may be due to side effects of a new class of anti-angiogenic drugs such as Avastin, which have less toxicity overall compared to older chemotherapy drugs but are associated with more bleeding problems, said Alok Khorana, M.D., assistant professor of Medicine in Hematology/Oncology at the James P. Wilmot Cancer Center at the University of Rochester.

“As if cancer patients don’t have enough to be concerned about, blood clots are a frequent but hidden complication, on par with infection,” Khorana said. “Sadly, some people die from preventable blood clots before the cancer itself advances.”

A blood clot in the leg, lung or hidden deep within veins is an ominous health threat, usually associated with heart or circulatory illness. A unique collaboration between oncologists and cardiologists at the University of Rochester uncovered important links between cancer and the vascular system that helps to explain how blood clots develop, why some cancer patients are susceptible, and how to prevent them.

Some of their research findings were presented at the International Society of Thrombosis and Haemostasis meeting in Geneva, Switzerland, on July 10, 2007. Later this year, based on input from the Rochester experts, the American Society of Clinical Oncology will publish its first set of guidelines for cancer specialists on clot prevention.

Khorana and colleagues discovered five variables that offer clues to a cancer patient’s risk of clots: site of cancer (pancreas, stomach, brain and lung are worst); body mass index above 35; and three measures within a blood sample including platelet, hemoglobin and white blood cell count. Patients at higher risk are candidates to receive blood thinners.

They also determined that a key to preventing clots lies within a certain biomarker called tissue factor (TF). The TF protein regulates clotting in normal blood cells, but it’s over-expressed by solid tumors and in some types of heart disease.

Researchers hope to develop a blood test that could be obtained at the time of tumor biopsy that would analyze TF and predict the likelihood of dangerous clots. They have already shown the potential benefit of such a test: pancreatic cancer patients with high TF expression had a venous thromboembolism rate of 26.3 percent compared with 4.5 percent of patients with low TF expression, according to a study published in May 2007 in the journal Clinical Cancer Research, by the Rochester group.

The National Cancer Institute funded the URMC development of the risk model for blood clots. Khorana is a leader in the Cancer-Associated Thrombosis Study Group at the University’s Wilmot Cancer Center. http://www.urmc.rochester.edu/cancer-center/researchers/research-accomplishments/thrombosis/index.cfm

Colleagues include: Charles Francis, M.D., professor of Medicine and director of the Hemostasis and Thrombosis program; Mark B. Taubman, M.D., chairman and Charles E. Dewey professor of Medicine; Manish Kohli, M.D., a Wilmot oncologist; and former Wilmot oncologist Gary Lyman, M.D., M.P.H., who recently joined Duke University.

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Leslie Orr
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