Plasma Tissue Factor Activity in lung cancer patients predicts venous thrombo-embolism and poor overall survival

Background Biomarkers to identify lung cancer (LC) patients with high risk of venous thromboembolism (VTE) are needed. Objectives To evaluate the usefulness of plasma Tissue Factor Activity (TFA) and D-dimer levels for the prediction of VTE and overall survival (OS) in patients with LC. Patients/Methods In a prospective multicenter observational cohort of consecutive LC patients, TFA and D-dimer were measured at diagnosis before any cancer treatment (V1) and between 8 to 12 weeks after diagnosis (V2). Results Among 302 patients, 38 (12.6%) experienced VTE within the first year after diagnosis. V1-TFA and V1-D-dimer were significantly (p=0.02) higher in patients who presented VTE within 3 months than in patients without VTE: V1-TFA were 2.02 [25th percentile=0.20 – 75th percentile=4.01] vs 0.49 [0.20 – 3.09] ng/mL and V1-D-dimer were 1.42 [0.64 – 4.40] vs 0.69 [0.39 –1.53] μg/mL, respectively. Cut-offs of 1.92 ng/mL for TFA and 1.26 μg/mL for D-dimer could discriminate both groups of patients. In multivariate analysis, V1-TFA >1.92 ng/mL was the only significant predictor of VTE risk at one year (hazard ratio=2.10, 95%CI 1.06–4.16, p=0.03). V2-TFA, quantified in 251 patients, decreased significantly compared to V1-TFA (0.20 vs 0.56 ng/mL, p <0.05), but a level of V2-TFA >0.77 ng/mL could predict VTE in the following 3 months. Median OS was worse for patients with V1-TFA >1.92 ng/mL (14.6 vs 23.8 months) and V1-D-dimer >1.26 μg/mL (13.8 vs 24 months) (p<0.001). Conclusions High plasma TFA levels are associated to the occurrence of VTE within the next 3 months and poor survival.