Figure 1.
Pathogenesis of the prothrombotic state in cancer patients (adapted from (1) with modifications). The central role of the tumor cell is illustrated, since: a) It directly interacts with platelets (P) inducing their aggregation; b) it interacts with vascular endothelial cells through several cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), which induce the expression of tissue factor (TF) by the endothelial cells, as well as the release of von Willebrand's factor (vWf), of leukocyte adhesion molecules, of platelet activating factor (PAF) and of plasminogen activator inhibitor type-1 (PAI-1), while at the same time down-regulating the expression of thrombomodulin, protein C (PC) receptor and tissue plasminogen activator (tPA); c) it stimulates leukocytes to produce TF and cytokines (TNF-α, IL-6); d) it directs the expression of procoagulants of TF, of cancer procoagulant (CP), of factor V receptor (FVr) and of mucin. The levels of IL-6, TNF-α, PAI-1 and VEGF (shown in bold) have been associated with carcinogenesis in the oral region by genetic association studies (12, 13, 42, 43).