Thromboembolic Disorders as a Consequence of Cancer

Abstract

Cancer cells and coagulation system are strictly connected. General prothrombotic mechanisms are related both to the host response to cancer and to the procoagulant activity of cancer cells (Fig. 4.1). Host-related factors include the acute-phase reaction, paraprotein production, inflammation, necrosis, and hemodynamic disorders. Malignant cells can activate blood coagulation in several ways. They can produce: procoagulant factors as tissue factor (TF) and cancer procoagulant factor (CP), which are the most powerful procoagulant observed; microparticles (MP); inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1); pro-angiogenic factors as vascular endothelial growth factor (VEGF), which promote both endothelial prothrombotic alterations and angiogenesis. VEGF is an indirect procoagulant that increases microvascular permeability, reprograms gene expression, and promotes the survival of endothelial cells; the resulting increased vascular density plays a key role in the pathophysiology of many cancers. The same procoagulant factors contribute to tumor progression. Also platelets, endothelial cells, and neutrophils of host cells are stimulated to express procoagulant activity. Thus, thromboembolism frequently complicates the course of malignancy and can be the first symptom of cancer [1, 2].