10091-COT-12 ELUCIDATING THE PATHOPHYSIOLOGY OF POST-OPERATIVE VENOUS THROMBOEMBOLISM IN IDH-WILDTYPE MALIGNANT GLIOMAS

Abstract BACKGROUND We have previously reported elevated expression of podoplanin and high incidence of post-operative venous thromboembolism (VTE) in IDH-wildtype gliomas (Watanabe et al., World Neurosurgery, 2019). Podoplanin binds to C-type lectin-like receptor-2 (CLEC-2) on the surface of platelets and induces platelet aggregation, potentially leading to the development of VTE. In the present report, we monitor serum podoplanin and CLEC-2 after surgery in malignant glioma patients to directly determine if this is the cause of post-operative VTE. METHODS Fourty-four malignant glioma patients undergoing surgery at the Department of Neurosurgery, Niigata University Hospital between April, 2018 and August, 2020 were assessed. Platelet counts as well as serum D-dimer, podoplanin, soluble CLEC-2, and C2PAC index (soluble CLEC-2 divided by platelet count) were measured within 10 days after surgery. Serum podoplanin and soluble CLEC-2 were assessed by enzyme-linked immunosorbent assay (ELISA). Values for IDH-wildtype glioma patients and IDH-mutant glioma patients were compared to patients undergoing microvascular decompression (MVD) and healthy volunteers (HV). RESULTS Post-operative VTE was observed in 8 out of 35 (23%) IDH-wildtype glioma patients, compared to 1 out of 9 (11%) IDH-mutant glioma patients. Serum soluble CLEC-2 levels (p = 0.0004) and C2PAC index (p = 0.0002) were significantly elevated in IDH-wildtype glioma patients compared to IDH-mutant glioma, MVD and HV groups. A C2PAC index threshold of 3.7 provide an 87.5% sensitivity and 51.9% specificity to predict post-operative VTE in IDH-wildtype gliomas. We serially monitored podoplanin and soluble CLEC-2 in select patients, and found that podoplanin is transiently elevated, followed by soluble CLEC-2 after surgery. CONCLUSION Platelet aggregation due to the activation of podoplanin-CLEC2 axis leads to post-operative VTE in IDH-wildtype malignant glioma patients. The C2PAC index is a potential biomarker for the early detection of VTE after surgery in these patients.