Plasmin generation kinetics reveal a hyperfibrinolytic phenotype in patients with pancreatic ductal adenocarcinoma

Background Thromboembolic complications are common in patients with pancreatic cancer, with up to 20% of patients developing venous thromboembolism (VTE). While hypercoagulation in pancreatic cancer has been widely studied, fibrinolysis is less well characterized. Plasmin generation (PG) is a novel approach to assess fibrinolytic activity and may provide new insights into thrombotic risk in this population. This study aimed to compare the fibrinolytic profile of patients with pancreatic cancer with that of healthy individuals. Methods This single-center cohort study included patients with advanced pancreatic cancer initiating chemotherapy at Maastricht University Medical Center between 2022 and 2023. Plasma samples were obtained before chemotherapy (t0) and eight weeks later (t8). PG and thrombin generation (TG) were measured, TG/PG ratios were calculated to evaluate the balance between coagulation and fibrinolysis. Thromboembolic events were recorded for 6 months. Results In total, 18 patients with pancreatic cancer and 18 healthy subjects were included. At baseline, patients showed higher endogenous plasmin potential (EPP) and higher plasmin peak levels compared with controls, while PG remained elevated at t8 despite chemotherapy. PG lag time was prolonged in patients. Patients showed an increased TG/PG ratio for endogenous thrombin/plasmin potential. Five patients (28%) developed thromboembolic events. Although PG parameters were not associated with thromboembolic events, patients who developed thromboembolic events showed lower TG/PG potential ratios. Conclusions Patients with pancreatic cancer have a disbalance in their fibrinolytic profile, with a delayed and increased capacity to generate plasmin. Future studies are required to assess whether PG associates with thromboembolic disease and survival.