Thrombotic risk from chemotherapy and other cancer therapies

Abstract

Cancer patients have an increased risk of thrombosis. The development of cancer thrombosis is dependent on a number of factors including cancer type, stage, various biologic markers, and the use of central venous catheters. In addition, cancer treatment itself may increase thrombotic risk. Tamoxifen increases the risk of venous thromboembolism (VTE) by two- to sevenfold, while an impact on risk of arterial thrombosis is uncertain. Immunomodulatory imide drugs (IMiDs) such as thalidomide and lenalidomide increase the risk of VTE in patients with multiple myeloma (MM) by about 10–40% when given in combination with glucocorticoids or other chemotherapy agents; the risk of VTE in MM patients treated with IMiD-containing regimens necessitates that such patients receive thromboprophylaxis with aspirin, low-molecular-weight heparin, or warfarin. Among cytotoxic chemotherapy agents, cisplatin, and to a lesser extent fluorouracil, has been described in association with thrombosis. l-asparaginase in treatment of acute lymphoblastic leukemia is significantly associated with increased thrombosis particularly affecting the CNS, which may be due to acquired antithrombin deficiency; at some centers, plasma infusions or antithrombin replacement is used to mitigate this. Bevacizumab, an inhibitor of vascular endothelial growth factor, increases arterial and possibly venous thrombotic risk, although the literature is conflicting about the latter. Supportive care agents in cancer care, such as erythropoiesis-stimulating agents, granulocyte colony stimulating factor, and steroids, also have some impact on thrombosis. This review summarizes the mechanisms by which these and other therapies modulate thrombotic risks and how such risks may be managed.