Malignancy, whether in the form of a solid tumor or hematologic neoplasm, constitutes a significant risk for hypercoagulability. Venous and arterial thromboembolic diseases are important causes of death and morbidity in individuals with cancer.1,2,3,4 It is estimated that venous clots complicate the clinical course of about 20% of all patients diagnosed with or treated for a malignancy,5,6 and even that figure may underestimate the problem, given autopsy findings of thrombosis in as many as 50% of patients with cancer.7
Not only does known malignancy pose an increased risk of later venous thromboembolism (VTE), but there are also substantial data supporting thromboembolism as an epiphenomenon of cancer, occasionally occurring months to years ahead of the other clinical manifestations of malignancy.7 The questions of how clinicians should respond to such a warning is, in itself, the subject of considerable research.
Although the relationship of hypercoagulability and neoplasm has been known for centuries,8 our understanding of the pathophysiologic mechanisms underlying this relationship continues to evolve. The linkage is multifactorial; with evidence supporting multiple mechanisms, including active clotting factors released by the neoplastic cells and by the healthy host cells in response to the malignancy; effects of the cytotoxic therapies instituted; or by the therapeutic interventions of cancer treatment, including immobilization, infection, frequent hospitalization, and surgery.
This chapter aims to provide readers with an introduction to some of the key points in the relationship between malignancy and thromboembolism. It begins with an overview of the historical context of this association and then outlines the accumulation of data supporting the broad clinical impact and incidence of hypercoagulability in this special population, an endeavor that requires estimating the incidence of VTE in individuals with cancer as well as the incidence of otherwise occult cancer in individuals with embolism. The next section attempts to clarify what is currently known about pathophysiology of hypercoagulability in cancer, including the risk conferred by certain tumor cell characteristics and the growing understanding of treatment-related risk. It summarizes the current recommendations on the prophylaxis of patients to prevent clots and the data underpinning the current standards for treatment in these patients. Finally, there will be a short review of the evidence that suggests a survival benefit of anticoagulation in patients with cancer, independent of a decrease in clot risk.
The 19th century French internist, epidemiologist, and lecturer Armand Trousseau is widely credited with the clinical observation that hypercoaguability is often associated with both solid tumors and malignancies of the hematopoetic systems. Trousseau's conclusions were likely informed by the 1823 writings of Jean-Baptiste Bouillaud, a professor of the Hopital de la Charite, who years before had described three cancer patients with "caillot fibrineau," or fibrin clots induced by the cancer process. Indeed, the relationship may well have been known long before. One ...