Extracellular vesicle tissue factor and venous thromboembolism outcomes in pancreatic cancer patients: A systematic review.

Abstract

780 Background: Pancreatic cancer has the highest risk of venous thromboembolism (VTE) among all cancers, with incidence rates ranging from 16 to 22% within twelve months of diagnosis. VTE is the second leading cause of mortality in pancreatic cancer. Yet, prophylactic anticoagulation remains underutilized, largely due to the lack of consensus on optimal candidate selection. Extracellular vesicle-derived tissue factor (EV-TF), including microparticle-associated forms (MP-TF), has emerged as a potential mediator of cancer-associated thrombosis (CAT) likely through activation of the coagulation cascade. This systematic review assesses the association between EV-TF/MP-TF activity levels and VTE events in pancreatic cancer patients. Methods: A systematic review was conducted according to PRISMA guidelines. PubMed, Embase, and ClinicalTrials.gov were searched for studies published from January 2001 to January 2025. We included prospective cohort and observational studies that examined EV-TF/MP-TF activity levels and VTE incidence in pancreatic cancer populations, excluding case reports and non-human studies. Data on patient characteristics, EV-TF/MP-TF activity levels, EV-TF/MP-TF measurement methods, and VTE incidence rate were extracted. Results: Seven studies met inclusion criteria, including 637 pancreatic cancer patients. VTE incidence across studies ranged from 6.6% to 44.5%, with most reports between 13-25% (Mean 20.5, Median 19.4). EV-TF/MP-TF activity levels were consistently higher in pancreatic cancer patients relative to controls, and all seven studies demonstrated positive associations between elevated EV-TF/MP-TF activity levels and VTE risk. Moik et al. reported that high EV-TF activity doubled overall VTE risk (subhazard ratio [SHR] 2.0), rising to SHR 4.1 in pancreatic subgroups. Kobayashi et al. identified TF ≥100 pg/mL as an independent predictor of CAT (RR=5.54). Further, multiple studies found significant correlations between elevated EV-TF/MP-TF activity levels and reduced overall survival. Heterogeneity in measurement methodologies and cutoff values was noted across studies. Conclusions: EV-TF and MP-TF are promising biomarkers for VTE prediction in pancreatic cancer, showing a consistent association with increased thrombotic risk and mortality. However, heterogeneity in vesicle isolation and TF quantification limits comparability across studies and underscores the need for standardized assays. These findings reinforce the promise of EV-TF activity as a biomarker for cancer-associated thrombosis risk, warranting further investigation in translational and clinical contexts. Incorporating EV-TF into predictive models could enable precision thromboprophylaxis, while therapies targeting TF-driven pathways may hold promise for reducing VTE and disease progression.