Venous thromboembolism in malignant gliomas

Abstract

Malignant gliomas are associated with a very high risk of venous thromboembolism (VTE). While many clinical risk factors have previously been described in brain tumor patients, the risk of VTE associated with newer anti-angiogenic therapies such as bevacizumab in these patients remains unclear. When VTE occurs in this patient population, concern regarding the potential for intracranial hemorrhage complicates management decisions regarding anticoagulation, and these patients have a worse prognosis than their VTE-free counterparts. Risk stratification models identifying patients at high risk of developing VTE along with predictive plasma biomarkers may guide the selection of eligible patients for primary prevention with pharmacologic thromboprophylaxis. Recent studies exploring disordered coagulation, such as increased expression of tissue factor (TF), and tumorigenic molecular signaling may help to explain the increased risk of VTE in patients with malignant gliomas.

Fig. 1

Normal brain tissue constitutively expresses tissue factor (TF), and expression is increased on malignant brain tissue cells. In this way, TF may play a role in tumor growth. TF circulates on microparticles (TF-MPs) that are shed during cellular activation or apoptosis. Circulating TF-MPs may be derived from both malignant brain tissue, as well as from upregulated, host cell-derived sources.