Hypercoagulability Predicts Survival and Reflects NET-Associated Thromboinflammation in Advanced Pancreatic Cancer.

Background

Cancer-associated thrombosis is a major complication in pancreatic cancer; however, its true burden and prognostic significance remain unclear, largely owing to under-detection of asymptomatic events. In addition, the clinical relevance of cancer-related hypercoagulability and neutrophil extracellular traps (NETs), which may link thrombosis and tumor biology, has not been adequately evaluated in advanced pancreatic cancer.

Methods

In this prospective study, newly diagnosed patients with unresectable pancreatic ductal adenocarcinoma underwent systematic screening for venous thromboembolism (VTE) at baseline, followed by longitudinal surveillance. Circulating coagulation markers and NET-related biomarkers were analyzed. Associations among VTE, hypercoagulability, NET-related biomarkers, and overall survival (OS) were evaluated.

Results

Among 134 patients, VTE was detected at diagnosis in 28.4%, with the majority being asymptomatic. Hypercoagulability and NET-related biomarkers were significantly associated with VTE occurrence. Patients with baseline VTE (6.2 vs. 12.1 months, p = 0.002) and hypercoagulability (7.7 vs. 15.2 months, p = 0.002) demonstrated shorter OS. In multivariate analysis, hypercoagulability, but not baseline VTE, remained independently associated with inferior OS (hazard ratio 2.03, 95% confidence interval 1.27-3.27). Notably, the adverse prognostic impact of hypercoagulability was consistently observed across nearly all predefined clinical subgroups. Furthermore, a reduction in or normalization of D-dimer levels following anticoagulant therapy was associated with prolonged survival.

Conclusions

Hypercoagulability, rather than overt thrombotic events, independently predicts survival outcomes in advanced pancreatic cancer. These findings support a biology-driven approach to thrombosis assessment and indicate that monitoring and therapeutic modulation of hypercoagulability may improve risk stratification and clinical management in this population.