Largest Biomarker Study for Cancer-Related Blood Clots Finds Circulating Tissue Factor Significant

Tumor cells push the body toward a procoagulant state

Venous thromboembolism (VTE), which includes deep venous thrombosis and pulmonary embolism, is a common but underestimated complication for cancer patients. Once patients develop VTE, even when treated with anticoagulation, they are at high risk for a recurrent episode.

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Clinical guidelines recommend extended low-molecular-weight heparin (LMWH) monotherapy for up to six months, for instance, but studies have shown the chance of a second clot is still high — between 7 and 9 percent.

With this in mind, Alok A. Khorana, MD, Director of Cleveland Clinic Cancer Center’s Gastrointestinal Cancer Program, and colleagues decided to look for a biomarker that would identify patients at high risk for recurrent VTE. Their analysis, which was recently published in the Journal of Clinical Oncology, is the largest biomarker study of cancer-recurrent VTE to date.

“We tested for a number of biomarkers and found at least one and maybe two significantly associated with recurrent VTE,” says Dr. Khorana. “One that was definitely associated was high levels of circulating tissue factor (TF) at the time of initial thrombosis.”

Tissue factor activates blood clotting process

To find biomarkers, Dr. Khorana and colleagues analyzed blood samples from 800 patients who were part of the Comparison of Acute Treatments in Cancer Hemostasis (CATCH) trial evaluating different anticoagulant treatments for cancer patients with VTE.

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They found that higher levels of circulating TF at the time of the initial thrombosis were associated with a greater likelihood that patients would develop recurrent VTE. Tissue factor is a protein that plays a role in the process of blood clotting. They also found that C-reactive protein was borderline significant.

Tumor cells express TF and often activate the body’s coagulation system, says Dr. Khorana. “By increasing the level of circulating procoagulants and decreasing the level of anticoagulants, they change the body toward a more procoagulant state.”

More intense anticoagulation therapy

Measuring TF is somewhat controversial. “We don’t quite know the best way to do it,” says Dr. Khorana. His team used the commercially available assay ELISA so their study could be more easily repeated.

There are ongoing trials to determine the best anticoagulation treatments, and Dr. Khorana and his team hope such investigations either confirm or refute their findings.

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Pinpointing biomarkers for recurrent VTE is important because the condition can be deadly. Some researchers have proposed using the Ottawa score, a clinically based risk-assessment model, but studies have shown it is inconsistent in predicting recurrent VTE — thus the need for more definitive predictors or biomarkers.

“You want to patients at risk for recurrent VTE on a more intense anticoagulation treatment or a longer period of treatment,” he says. “If clots occur or recur they can be life-threatening, especially pulmonary embolism. Hence the need to manage this very carefully.”