Abstract Hemostasis lies at the edge between physiology and cancer, where the coagulation cascade—initiated by tissue factor, thrombin generation, and fibrin deposition—shifts from vascular repair to tumor promotion. The interplay between coagulation and cancer is now recognized as a two-way street, with tumor cells activating the clotting system and coagulation components feeding back to promote malignancy. Tumor cells not only foster proliferation and invasion by overexpressing tissue factor and activating Protease-Activated Receptors (PAR1/PAR2) signalling, but they also induce endothelial cells and fibroblasts in the tumor microenvironment (TME) to produce coagulation factors (TF, FV, prothrombin) through cytokines (VEGF, IL-1β), NF-κB signalling, and hypoxia factor (HIF-1α). Generated thrombin and FXa drive MAPK/PI3K pathways, angiogenesis (VEGF upregulation), and immune evasion by suppressing T-cell chemokines (CXCL9/10/11) and fostering M2 macrophages. Platelets, activated by tumor-associated coagulation, release PDGF, TGF-β, and VEGF to promote stromal remodeling and exclude cytotoxic T cells via PD-L1 transfer, while fibrin matrices shield tumors and recruit suppressive myeloid cells. This bidirectional interplay creates a protumoral niche supporting both primary growth and metastatic dissemination, where circulating tumor cells (CTCs) exploit platelet cloaking against shear stress and NK cells. Cancer hypercoagulability is a known state which elevates venous thromboembolism, with D-dimer as a prognostic biomarker linking thrombosis to aggressive disease. Targeting this hemostasis–cancer axis—via TF inhibition, anticoagulation, or antiplatelet therapy—offers therapeutic promise to disrupt proliferation, immune escape, and metastasis.
Galardi et al. (Tue,) studied this question.