Chapter 56: Cancer-Associated Thrombosis

VENOUS THROMBOEMBOLISM

Scope of the Problem

Pulmonary embolism (PE) and deep venous thrombosis (DVT) are manifestations of venous thromboembolism (VTE). Approximately 20% of all VTEs are associated with cancer, and cancer increases the risk for VTE four- to sixfold. Surgery, chemotherapy, hormonal therapy, growth factors, angiogenesis inhibitors, immunomodulators, erythropoietic agents, and central venous catheters (CVCs) contribute to cancer-associated VTE (¹). Risk of VTE is associated with the type of cancer and its clinical stage, with glioblastoma, stomach cancer, pancreatic cancer, lung cancer, gynecologic cancer, and leukemia frequently associated with VTE, and early-stage breast cancer, prostate cancer, and melanoma least commonly associated with VTE (¹). Cancer-associated VTE is rarely lethal within 6 months of diagnosis and treatment (²), but it is often undiagnosed, and its onset can be associated with considerable mortality. Venous thromboembolism was the death certificate–attributed cause of death for 0.21% of patients with cancer in a large population-based death certificate review (³), the cause of 3.5% of 141 deaths recorded among 4,466 community hospital–treated ambulatory patients with cancer (⁴), and the objectively documented cause of death among 1.5% of all patients with cancer managed by a single cancer center (⁵).

Diagnosis

Clinical presentations of VTE are not specific. Most patients with DVT have unilateral leg swelling and tenderness, and most patients with PE have abrupt-onset dyspnea and pleuritic chest pain. These symptoms are nonspecific, especially in patients who have cancer. Scoring systems developed to estimate pretest probability of DVT and PE (like the Well’s scores) can be used to rule out VTE in patients with cancer, but the likelihood of finding a normal D-dimer level among patients with cancer is less than 30%, and elevated D-dimers are of no positive predictive value (⁶). Doppler/compression ultrasound is the preferred method to diagnose DVT, although magnetic resonance imaging (MRI) and computed tomography (CT) may be required in special circumstances, such as internal iliac vein or vena cava thrombosis. High-resolution CT or CT angiography is the best method for diagnosing PE (⁷), and it offers the advantage of providing additional information regarding synchronous thoracic pathology that may confound the diagnosis of PE. Conversely, up to 5% of all chest CTs done for cancer staging, monitoring, and surveillance show asymptomatic incidental PEs (⁸).

Prevention

Pharmacological VTE prophylaxis should be considered in every hospitalized patient with cancer for whom there is no contraindication (⁸). Contraindications to pharmacological anticoagulation are absolute (recent central nervous system bleed, intracranial or spinal lesion at high risk for bleeding, or major active bleeding: more than 2 units transfused in 24 hours) or relative (chronic, clinically significant measurable bleeding >48 hours; platelets <50,000/μL; platelet dysfunction [uremia, medications, dysplastic hematopoiesis]; recent major operation at high risk for bleeding; underlying hemorrhagic coagulopathy; ...