Mechanisms of Hemostatic System Activation by Tumor Cells Involves Different Hemostatic Pathways. Tumor cells produce procoagulant, fibrinolytic, and platelet-aggregating activities and release proinflammatory and proangiogenic cytokines and procoagulant microparticles. Tumor cells interact with host vascular and blood cells (i.e., platelets, leukocytes, and endothelial cells) by means of direct adhesion, which activates the prothrombotic properties of these cells. Tumor cell-derived TF plays a central role in the generation of thrombin, but TF can also contribute to tumor growth and metastasis by coagulation-independent mechanisms, including influencing the expression of VEGF by the malignant cells and vascular cells and activating the PAR-2 signaling.The generation of activated coagulation proteases (FVIIa, FXa, thrombin) and the formation of fibrin represent coagulation-dependent mechanisms of tumor progression, as they promote neo-angiogenesis and tumor proliferation. Fibrin coats also protect circulating cancer cells from attack by the host immune system.