Cancer and Venous Thromboembolic Disease: A Review

Abstract

Venous thromboembolism (VTE), including deep-vein thrombosis and pulmonary embolism, represents a major cause of morbidity and mortality in cancer patients. Patients with cancer are six times more likely to develop VTE than their noncancer counterparts, and VTE is the second leading cause of death in cancer patients. Despite the publication of major consensus guidelines setting out recommendations for thromboprophylaxis in cancer patients, there remains a gulf between these guidelines and clinical practice. In general, thromboprophylaxis is recommended for most patients hospitalized with active cancer. Furthermore, outpatient thromboprophylaxis may be used in carefully selected high-risk ambulatory patients. Certain areas of controversy still remain. Although low-molecular-weight heparin has been shown to be superior to vitamin K antagonists in cancer patients, the role of direct oral anticoagulants is still uncertain. Moreover, recurrent thromboembolism, bleeding, and thrombocytopenia are frequently seen in cancer patients. Optimal anticoagulation in such instances presents a major challenge to clinicians. Modern computed tomography techniques have resulted in an increase in the detection of "incidental" VTE. Despite a growing body of evidence promulgating standard anticoagulant treatment in such cases, these cases present further challenges for members of the multidisciplinary team. The Oncologist 2017;22:199-207Implications for Practice: This article discusses venous thromboembolism (VTE) in patients with malignancy. Practical guidance is offered on how to prevent, diagnose, and treat VTE in cancer patients. The management of "challenging" cases of VTE is also discussed.

Keywords: Cancer; diagnosis; treatment; venous thromboembolism.

Figure 1.

Mechanisms underlying the cancer‐associated procoagulant state. Cancer‐mediated hypercoagulability occurs as a consequence of direct activation of procoagulant pathways by cancer cells (mediated by aberrant tumor cell TF expression, release of tumor cell‐derived, TF‐expressing microparticles, cancer procoagulant, and other cell surface proteases) or from indirect systemic effects of cancer on a variety of cell types, including leucocyte, endothelial cells, and platelets. In various malignancies, neutrophils are “primed” to release their contents in the form of NETs, resulting in direct activation of procoagulant pathways, platelet activation, and inhibition of naturally occurring anticoagulant pathways, including tissue factor pathway inhibitor. As a consequence of these various direct and indirect mechanisms, patients with cancer have an elevated risk for venous thromboembolism. Abbreviations: FXa, factor Xa; NET, neutrophil extracellular trap; TF, tissue factor.