Cancer and thrombosis: mechanisms and treatment

Standard venous thromboembolic event (VTE) treatment practices including the use of intravenous unfractionated heparin (UFH) for initial anticoagulation, oral warfarin for chronic anticoagulation, and the prescription of only 3 to 6 months total therapy may not be optimal in the setting of active cancer and ongoing anti-cancer therapy. Challenges of VTE management in cancer patients include heparin resistance due to excess circulating acute-phase proteins, increased recurrence rates during and following standard-intensity warfarin therapy, limited venous access to support therapeutic monitoring, and anticoagulation intensity-independent increased bleeding rates during anticoagulation. Bleeding during anticoagulation is of particular concern in the treatment of cancer patients with disease- or chemotherapy-related thrombocytopenia, central nervous system involvement, or recent invasive procedures. Low-molecular weight heparins (LMWH) have been shown to be at least as effective and safe for initial anticoagulation compared with UFH in persons with acute VTE and have gained popularity in the setting of VTE in cancer. LMWHs have the advantage of less non-specific protein binding, subcutaneous weight-based dosing without the need for monitoring in most cases, and probably less heparin-induced thrombocytopenia. Recent trials have demonstrated efficacy superiority of select LMWHs in place of oral warfarin for long-term anticoagulation in the cancer patient. The potential for anti-tumor effects and a survival advantage associated with select classes of anticoagulant agents is actively being investigated.