Mechanisms of disease: the impact of antithrombotic therapy in cancer patients

Venous thromboembolism is a common complication in patients with malignant disease. It is associated with a systemic hypercoagulable state that is secondary to tumor elaboration of tissue factor (the physiological initiator of blood coagulation), activation of other procoagulant mechanisms and downregulation of anticoagulant mechanisms. The consequent generation of activated coagulation serine protease in the peritumoral environment influences tumor growth, invasion, metastasis and angiogenesis. The use of antithrombotic agents, such as the low-molecular-weight heparins, might influence survival in cancer patients through several mechanisms. These mechanisms include a reduction in the frequency of overt and silent fatal thromboembolic events, interference with the activation of blood coagulation and generation of coagulation serine proteases that affect the tumor phenotype, and direct cellular effects of heparin on both epithelial and endothelial tumor elements.