Host-tumor cell interaction and the hypercoagulable state of cancer. Tissue factor (TF) and cancer procoagulant (CP) are synthesized and expressed on the surface of tumor cells. The effects of these tumor cell procoagulants (made by both solid tumor and leukemic cells) are enhanced by the production of proangiogenic cytokines such as interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF), both by the tumor cells and local endothelial cells. Release of proinflammatory cytokines, such as tumor necrosis factor (TNF-α) and interleukin-1 (IL-1b), by the tumor cells and host inflammatory cells further stimulates the hypercoagulable state, as follows. These cytokines are indirect procoagulants by virtue of their ability to convert the anticoagulant endothelium to a procoagulant endothelium by (1) down-regulation of thrombomodulin (TM) expression and (2) increased endothelial cell synthesis of TF and plasminogen activator type 1 (PAI-1). Generation of fibrin at the endothelium enhances thrombogenesis by inducing additional TF and IL-8 production by the injured endothelial cells. (Figure modified and reproduced from Falanga and Rickles,² with permission of the publishers).