Circulating Tissue Factor Identified as Predictive Biomarker of Cancer-Related Blood Clots

Recent work out of Cleveland Clinic's Center of Excellence in Thrombosis Research—an inter-institute partnership pairing physicians and researchers—offers new insight into how clinicians might better predict venous thromboembolism (VTE), a common and highly consequential complication of cancer.

VTE, which includes deep vein thrombosis and pulmonary embolism, is a blood clot that occurs within a vein. In malignancy, VTE is associated with both increased morbidity and mortality. It is currently treated with anticoagulants—a class of drug commonly referred to as blood thinners—including heparin and warfarin. But even with such treatment, the rate of VTE recurrence in patients living with cancer is significant. Current risk assessment models, including the commonly used Ottawa score, inconsistently and often under-predict this recurrence.

Researchers led by Alok Khorana, MD, co-director of the Center of Excellence in Thrombosis Research and staff member in the Taussig Cancer Institute, set out in search of a better predictive biomarker or clinical risk factor.

His team analyzed 800 blood samples collected from people previously enrolled in the Comparison of Acute Treatments in Cancer Hemostasis (CATCH) trial, which investigated the safety and efficacy of two drug therapies for VTE treatment in cancer patients. The researchers looked for biological markers that were more common among patients who later went on to experience VTE again following treatment. They found that elevated levels of circulating tissue factor at the time of initial acute VTE is predictive of recurrent VTE in cancer patients who are receiving anticoagulation therapy. Circulating tissue factor catalyzes the blood coagulation cascade and is expressed in tumor cells. Other significant variables identified include venous compression from mass and hepatobiliary cancer—cancer of the liver, bile ducts and gallbladder—but their role and predictive value need to be investigated further.

Published in the Journal of Clinical Oncology, this work shows for the first time that circulating tissue factor may be an early indicator of recurrent VTE in cancer patients. In a clinical setting, this research discovery may help doctors better identify high-risk patients and tailor treatment, including prescribing more intensive anticoagulation therapies.

Dr. Khorana also holds the Sondra and Stephen Hardis Chair in Oncology Research and is Vice-Chair for Clinical Services of the Taussig Cancer Institute and Director of the Gastrointestinal Malignancies Program at Cleveland Clinic.