Venous thromboembolism in patients with glioblastoma: cancer and coagulation in concert

Abstract

Glioblastoma, IDH-wildtype, is the most common primary brain malignancy among adults. Due to its aggressive nature and hypercoagulable state, the risk of venous thromboembolism (VTE) is particularly high, with an incidence of up to 10-30% per year. Although the underlying genetic and cellular mechanisms are increasingly understood, current prophylactic treatment strategies sparsely include risk scores that aid in risk prediction at the individual level. Sequencing of tumor material, which is standard of care for tumor diagnostics, directly provides insight in genetic risk factors present. In combination with measurement of procoagulant extracellular vesicles (EVs), the patient’s individual hypercoagulable risk profile can be determined, which should be at the basis for personalized thromboprophylaxis. In glioblastoma, there are two procoagulant factors expressed by tumor cells that have been linked to VTE: Tissue Factor (TF), the initiator of extrinsic coagulation, and podoplanin, a transmembrane glycoprotein involved in platelet aggregation. This thesis focuses on the genetic and cellular background of VTE in glioblastoma patients, with a specific interest in the role of TF.