The role of anticoagulation in high grade gliomas: a systematic review

Abstract

Background: Patients with cancer have an increased risk of venous thromboembolic events (VTE), with particularly high prevalence among patients with glioblastoma (GBM). Patients who develop VTE have higher mortality compared with those without such events. It is necessary to better understand predictors of thromboembolic events in patients with high-grade gliomas in order to identify candidates for prophylactic anticoagulation. In patients with established VTE, therapeutic anticoagulation has been used; however, concerns remain regarding the risk of bleeding. Objective: To systematically review the evidence on the use of prophylactic and therapeutic anticoagulation in adults with glioblastoma, focusing on venous thromboembolism prevention or recurrence, and bleeding risk as outcomes. Methods: We conducted a systematic review in accordance with the PRISMA protocol up to September 25, following Cochrane-recommended methods to minimize publication bias. Searches were performed in PubMed, Embase, the International Clinical Trials Registry Platform, and MEDLINE using the terms “glioblastoma,” “anticoagulation,” “thromboembolism,” and “deep venous thrombosis.” The initial search identified 453 articles, of which 86 were related to anticoagulation. Ten studies addressing prophylactic and therapeutic anticoagulation were included. Results: Of 453 records identified, 86 underwent full-text review and 10 studies were included in our final analysis. Prophylactic anticoagulation showed a favorable safety profile, with low rates of major bleeding. Among 101 patients receiving thromboprophylaxis, only one developed VTE. Apixaban, dalteparin, tinzaparin, and aspirin-based strategies were generally well tolerated in selected cohorts. Prophylactic anticoagulation was associated with a low risk of bleeding. For therapeutic anticoagulation, a total of 437 patients were evaluated: 315 received low-molecular-weight heparin, 37 direct oral anticoagulants, 52 warfarin, and 4 unfractionated heparin, and 29 had no anticoagulant specified. Venous thromboembolism recurrence occurred in 7 of 252 patients (2.7%), while major bleeding was reported in 71 of 437 patients (16.2%). Risk of bleeding was lower with direct oral anticoagulants (8.1%) than with low-molecular-weight heparin (18.4%) or warfarin (15.3%), suggesting a more favorable safety profile for direct oral anticoagulants. Conclusion: The use of anticoagulants in patients with glioblastoma showed a favorable safety profile in this systematic review. Patients receiving prophylactic anticoagulation had a lower risk of thromboembolism. Therapeutic anticoagulation was not associated with an increased risk of bleeding and was associated with reduced VTE risk. The use of DOACs was associated with a lower incidence of thromboembolic events.