Circulating microparticle tissue factor, thromboembolism and survival in pancreaticobiliary cancers

Background: Tissue factor (TF), the physiologic initiator of coagulation, is over-expressed in pancreatic cancer, and is associated with a pro-coagulant and pro-angiogenic state. We hypothesized that in patients with pancreaticobiliary cancers (PBC), elevated circulating microparticle-associated TF (MP-TF) activity would be associated with thrombosis and worsened survival. Patients and Methods: Clinical data and plasma were obtained for consecutive patients with PBC seen at Roswell Park Cancer Institute from 2005-08. MP-TF activity levels were measured using a TF-dependent FXa generation assay. Results: The study population comprised 117 patients, including pancreatic (n = 80), biliary (n = 34) or unknown primary histologically consistent with PBC (n = 3). Of these, 52 patients (44.5%) experienced thromboembolism, including pulmonary embolism (n = 15), deep venous thrombosis (n = 21) and other arterial or venous events (n = 32). Mean TF was 2.15 (range 0.17- 31.01) pg/mL. Median survival was 98.5 days for MP-TF activity >= 2.5 pg/mL versus 231 days for MP-TF activity < 2.5 pg/mL (p < 0.0001). In multivariate analysis, elevated MP-TF activity was associated with both VTE (OR 1.4, 95% CI 1.1-1.6) and mortality (HR 2.5, 95% CI 1.4-4.5). Conclusions: Elevated circulating MP-TF activity is associated with thrombosis and worsened survival in patients with PBC. MP-TF activity as a prognostic biomarker warrants further prospective evaluation. (c) 2013 Published by Elsevier Ltd.