Nonbacterial Thrombotic Endocarditis in Cancer Patients: Pathogenesis, Diagnosis, and Treatment

Abstract

LEARNING OBJECTIVES1. Enumerate procoagulant factors present in malignancy and the risk for thromboembolic events.2. Describe the morbidity associated with nonbacterial thrombotic endocarditis.3. List the recommended evaluations and treatments for nonbacterial thrombotic endocarditis.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTThrombophilia is a well-described consequence of cancer and its treatment. The pathogenesis of this phenomenon is complex and multifactorial. Nonbacterial thrombotic endocarditis (NBTE) is a serious and potentially underdiagnosed manifestation of this prothrombotic state that can cause substantial morbidity in affected patients, most notably recurrent or multiple ischemic cerebrovascular strokes. Diagnosis of NBTE requires a high degree of clinical suspicion as well as the judicious use of two-dimensional echocardiography to document the presence of valvular thrombi. In the absence of contraindications to therapy, treatment consists of systemic anticoagulation, which may ameliorate symptoms and prevent further thromboembolic episodes, as well as control of the underlying malignancy whenever possible. The Oncologist 2007;12:518 -523 Disclosure of potential conflicts of interest is found at the end of this article.

Middle cerebral artery infarction in a cancer patient: a fatal case of Trousseau's syndrome

“…When macrophages interact with malignant cells, there is a release of cytokines such as interleukin-1, interleukin-6, and tumour necrosis factor that can lead to endothelial damage and thrombogenesis on viable surfaces. 6 Tumour cells may also secrete tissue factor and cysteine proteases with thromboplastin-like properties that activate coagulation factors VII and X. Finally mucin-producing adenocarcinomas can lead to direct non-enzymatic activation of factor X.…”

“…6 This may have been the underlying cause for the patient's massive MCA infarction and pulmonary embolism. Formally known as marantic endocarditis, the condition is characterised by sterile platelet and fibrin rich thrombi that form on previously undamaged heart valves.…”

“…8,10 Its pathogenesis is incompletely understood, but is possibly due to cytokine-mediated inflammatory valvular tissue injury that predisposes to thrombus formation. 6 For several reasons, NBTE is difficult to diagnose. Thus, though aortic and mitral valves are the most commonly affected, patients seldom have detectable cardiac murmurs.…”

“…Thus, though aortic and mitral valves are the most commonly affected, patients seldom have detectable cardiac murmurs. 6,11 Concomitantly, immunocompromised patients can suffer from infective endocarditis that confounds the diagnosis. Finally, transthoracic echocardiography is not sufficiently sensitive in detecting the smaller friable valvular vegetations of NBTE.…”

“…12 Careful selection of patients for transoesophageal echocardiography, the preferred diagnostic test, is claimed to be preferable. 6 Patients without end-stage malignancy, acceptable performance status of 3 or less on the Eastern Cooperative Oncology Group scale and with nondebilitating stroke are suitable candidates. For this patient, the diagnosis of NBTE was inferred in view of the negative culture and serology results and failed response to systemic antibiotics.…”