Tissue factor pathway inhibitor is associated with risk of venous thromboembolism and all-cause mortality in patients with cancer

Abstract

Venous thromboembolism (VTE) is a common complication in patients with cancer. Data on the role of natural inhibitors of coagulation for occurrence of cancerassociated VTE are limited, thus, we investigated the association of tissue factor pathway inhibitor (TFPI) with risk of VTE and all-cause mortality in patients with cancer. Total TFPI antigen levels were measured with a commercially available ELISA in patients included in the Vienna Cancer and Thrombosis Study, a prospective observational cohort study with the primary outcome VTE. Competing risk analysis and Cox regression analysis were performed to explore the association of TFPI levels with VTE and all-cause mortality. TFPI was analyzed in 898 patients (median age: 62 years [interquartile range, IQR: 53-68]; 407 [45%] women). Sixtyseven patients developed VTE and 387 died (24-month cumulative risk: 7.5% and 42.1%, respectively). Patients had median TFPI levels at study inclusion of 56.4ng/mL (IQR: 45.7-70.0), with highest levels in tumor types known to have a high risk of VTE (gastroesophageal-, pancreatic and brain-cancer: 62.0ng/mL [IQR: 52.0-75.0]). In multivariable analysis adjusting for age, sex, cancer type and stage, TFPI levels were associated with VTE risk (SHR per doubling: 1.63, 95%CI: 1.03-2.57). When patients with high and intermediate/low VTE risk were analyzed separately, the association remained independently associated in the high risk group only (SHR: 2.63, 95%CI: 1.40-4.94). TFPI levels were independently associated with all-cause mortality (HR: 2.36, 95%CI: 1.85-3.00). In cancer patients increased TFPI levels are associated with VTE risk, specifically in patients with high risk tumor types, and with all-cause mortality.