Fig. 1

Illustration summarising the major tumour procoagulant effects in pancreatic cancer. (1) Tissue factor (TF) expression and release of TF-positive microvesicles (TF + MV) (2) TF triggers the extrinsic pathway of coagulation leading to thrombin (FIIa) generation. (3) Heparanase (HPSE) removes glycocalyces containing tissue factor pathway inhibitor (TFPI), thereby enhancing TF activity. (4) Tumour-derived mucin and podoplanin (PDPN) activate platelets, which express phosphatidylserine (PS) on their surfaces (5), facilitating prothrombinase complex assembly and thrombin generation. Activated platelets present adhesion molecules that facilitate endothelial-platelet and platelet–leukocyte interactions that contribute to generation of platelet-rich microthrombi (6). Activated neutrophils release neutrophil extracellular traps (NETs) (7) that create a matrix for blood cell and MV adhesion which promote thrombosis and impair blood flow. Cell-free DNA (cfDNA) released from tumour cells or neutrophils provides a negatively charged surface that promotes activation of factor XII (FXII) (8). FXIIa initiates the intrinsic pathway of coagulation, providing an additional source of thrombin. Plasminogen activator inhibitor 1 (PAI1)—a potent inhibitor of fibrinolysis – can be released by pancreatic tumour cells, as well as by activated platelets (9)