Cancer and venous thromboembolism

Neoplastic cells can activate the clotting system directly, thereby generating thrombin, or indirectly, by stimulating mononuclear cells to synthesize and express various procoagulants. Clinical manifestations of increased thrombin generation may be accentuated by down-regulation of endothelial cell counterregulatory mechanisms, such as decreased hepatic synthesis of antithrombin III and protein C. Cancer cells and chemotherapeutic agents can injure endothelial cells, thereby intensifying hypercoagulability. In addition, normal endothelial cell function may be disrupted by various defects in platelet function. Currently, primary prevention of venous thrombosis should be considered for cancer patients (1) during and immediately after chemotherapy, (2) when long-term indwelling central venous catheters are placed; or (3) when hospitalization for cancer is characterized by prolonged immobilization, trauma, or surgery. Secondary prevention of recurrent venous thrombosis usually necessitates anticoagulation. In some patients with cancer, the condition is resistant to warfarin, and long-term adjusted high-dose heparin is required. For patients unable to tolerate heparin or warfarin because of major bleeding problems, placement of an inferior vena caval filter should be considered. The diagnosis of venous thrombosis may help to uncover previously occult carcinoma by prompting a complete physical examination, chest roentgenography, and mammography. However, extensive cancer screening with total-body computed tomography or magnetic resonance imaging has not been shown to be cost effective for patients with venous thrombosis.