PB0733 - Patients with pancreatic cancer have a disturbed whole blood thrombin generation profile

Background: Thromboembolic disease is a major complication in patients with pancreatic ductal adenocarcinoma (PDAC), causing morbidity and mortality. One in five patients with newly diagnosed PDAC develops a venous thromboembolism (VTE) and VTE development is associated with a decreased overall survival time. Patients with PDAC often have altered blood cell counts, which are further affected by systemic therapy. The high thromboembolic risk in patients with PDAC may be caused by pro-coagulant effects of pancreatic cancer on blood cells.

Aims: To investigate the impact of pancreatic cancer on blood cell dependent coagulation, using the whole-blood thrombin generation (WB-TG) assay, to further characterize the high thrombosis risk in this population.

Methods: The TROCOPAC study is a prospective observational case-control study. Before the initiation of systemic therapy (FOLFIRINOX or nab-paclitaxel-gemcitabine), blood was collected from patients with locally advanced or metastatic PDAC. WB-TG profiles of these patients were compared to healthy individuals. 18 patients with PDAC were included and 13 healthy individuals.

Results: In WB-TG, patients with PDAC have a significantly higher endogenous thrombin potential (ETP) than healthy individuals (2741 vs. 1760 nM*minutes, p=0.0041; figure 1A). The time to reach the thrombin generation peak is elongated in patients with PDAC when compared to healthy individuals (16.97 vs. 14.47 minutes, p=0.0197; figure 1B).

Conclusion(s): Patients with PDAC have an increased WB-TG ETP and prolonged WB-TG TTP in comparison to healthy individuals. The increased potential to generate thrombin corresponds with the high thrombosis incidence in PDAC. The elongated TTP on the contrary may explain the higher bleeding risk in those patients. We hypothesize that red blood cells and platelet abnormalities in PDAC disturb the thrombosis and bleeding homeostasis.