Cancer-related deep venous thrombosis: clinical importance, treatment challenges, and management strategies

Venous thromboembolic disease (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is an underdiagnosed and underappreciated clinical problem in cancer patients that results in significant patient morbidity and mortality. Standard treatment practices, including the use of intravenous unfractionated heparin (UFH) for initial anticoagulation, the use of 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 anticancer therapy. Challenges of VTE management in cancer patients include heparin resistance because of excess circulating acute phase proteins, increased recurrence rates during warfarin therapy (target international normalized ratio 2 to 3), limited venous access to support therapeutic monitoring, and increased bleeding rates during anticoagulation. Bleeding during anticoagulation is of particular concern in patients with disease- or chemotherapy-related thrombocytopenia, central nervous system involvement with cancer, and recent surgical intervention. Low-molecular-weight heparins (LMWHs) have been shown to be equally effective and safe for initial anticoagulation compared with UFH and have gained popularity, especially in the setting of VTE in cancer. LMWHs have the advantage of less nonspecific protein binding, subcutaneous weight-based dosing without the need for monitoring in most cases, and less heparin-induced thrombocytopenia. Recent clinical trials have shown LMWHs are at least as effective as oral warfarin for long-term anticoagulation in cancer patients. Interest in LMWHs and several new classes of parenteral and oral anticoagulants extends beyond the primary and secondary prevention of VTE and includes antiangiogenesis, metastasis prevention, and survival prolongation.