Podoplanin Expression and IDH-Wildtype Status Predict Venous Thromboembolism in Patients with High-Grade Gliomas in the Early Postoperative Period

Contrasts in Glioblastoma—Venous Thromboembolism versus Bleeding Risk

“…This is also consistent when adjusted for age, tumor grade and presence of hemiparesis, as the risk remains twice as high in patients with IDH wild-type compared to IDH mutation glioma [5]. A link between the IDH mutation status and frequency of VTE could be the podoplanin expression levels because IDH-mutant gliomas suppress the expression of podoplanin [5,[25][26][27][28] Yet, the perioperative measurements of prothrombin and partial thromboplastin times did not show any difference between the IDH wild-type and IDH mutant gliomas, suggesting that clotting factors have no functional differences [24]. Interestingly it was also found that tissue factor microparticle activity was elevated in IDH wild-type gliomas compared to IDH-mutant gliomas, and a positive correlation between the preoperative circulating tissue factor microparticle activity and the development of venous thromboembolism was reported [24].…”

Vascular complications in patients with brain tumors

“…More recently, attention has focused on the importance of podoplanin – an inducer of platelet aggregation – as an alternative mechanism mediating hypercoagulability in gliomas. Several reports have shown an increase in the risk of VTE in patients with high tumoral expression of this substance [11–13], and a preclinical study demonstrated release of podoplanin by glioblastoma cell lines in extracellular vesicles as well as increased podoplanin levels in the blood of 14 glioblastoma patients [14], also bridging the gap between this tumor-expressed protein and systemic hypercoagulability. The relative contributions of these two pathways to hypercoagulability in gliomas, and their role in other brain tumors, remains to be elucidated.…”

“…In addition to the classically described risk factors for VTE in brain tumors (in particular gliomas) including age, prior thrombotic events, limb paresis, tumor grade, and tumor size, more recent research has investigated how molecular characteristics influence the incidence of VTE. Multiple studies have found a lower risk in patients with IDH-mutant gliomas [2,12,13,15] -perhaps mediated by methylation of the F3 promoter and subsequent decrease in TF expression [15] or by downregulating podoplanin expression [14] -although some other reports have found the difference in risk between patients with and without IDH mutations not significant [3,16]. A large study in brain metastases demonstrated that risk factors for VTE are similar to those described for gliomas and other cancers, including immobilization, steroid use, obesity, exposure to chemotherapy after brain metastasis diagnosis, and certain primary histologies such as lung, renal cell carcinoma and unknown primary tumor [9 & ].…”

Mechanisms and biomarkers of cancer-associated thrombosis

“…In a separate study of newly diagnosed glioma patients, podoplanin tissue positivity (≥30% expression) and IDH1 mutant status were significantly correlated with subsequent VTE risk with low precision of estimated risk (OR 3.423, 95% CI 1.083-10.814; OR 0.101, 95% CI 0.010-0.975, respectively). 151 Podoplanin and IDH1 tissue expression are assessed histologically after immunostaining of tumor tissue. While these assays can be completed in the clinical setting, the invasive nature of tissue collection, especially in the setting of brain cancer, can delay and limit use of risk models.…”