Potential Biomarker of Recurrent Venous Thromboembolism in Patients Receiving Anticoagulants



In a biomarker analysis of the CATCH trial reported in the Journal of Clinical Oncology, Alok A. Khorana, MD, of the Cleveland Clinic, and colleagues found that elevated circulating tissue factor levels were associated with an increased risk of recurrent venous thromboembolism in cancer patients on anticoagulant therapy.

CATCH was a randomized trial in which 900 patients with acute symptomatic venous thromboembolism (recurrent in 8.4%) were randomized to receive tinzaparin (Innohep) at 175 IU/kg once daily or dose-adjusted warfarin for 6 months. The biomarker study assessed tissue factor enzyme-linked immunosorbent assay (ELISA), soluble P-selectin, D-dimer, FVIII, and C-reactive protein.

Elevated Risk

Among 805 patients with available tissue factor assay data, mean and median tissue factor levels were 72.5 pg/mL and 50.3 pg/mL (range = 15.6–4,798 pg/mL). Risk of recurrent venous thromboembolism was significantly higher among the 203 patients in the highest quartile of tissue factor (> 64.6 pg/mL) compared with all other 602 patients (19% vs 6%, relative risk = 3.3, P < .001).

In competing risk regression analysis of time to recurrent venous thromboembolism, adjusted for treatment assignment, region, history of venous thromboembolism, and metastatic disease, tissue factor in the highest quartile remained significantly associated with risk of recurrent venous thromboembolism (subdistribution hazard ratio [SHR] = 3.3, 95% confidence interval [CI] = 1.7–6.4). Highest quartile C-reactive protein (SHR = 2.3, 95% CI = 1.2–4.4), venous compression from mass (SHR = 3.1, 95% CI = 1.4–6.5), and hepatobiliary cancer (SHR = 5.5, 95% CI = 2.3–13.6) were also significantly associated with increased risk.

The investigators concluded: “This is the first report, to our knowledge, to describe [tissue factor] as a potential biomarker of recurrent [venous thromboembolism] in patients with cancer who are on anticoagulation treatment. A risk-adapted strategy could help identify high-risk patients who may benefit from more intensive anticoagulation approaches.”

The study was supported by Leo Pharma.

Khorana AA, et al: J Clin Oncol. December 28, 2016 (early release online).



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