Management of Venous Thromboembolism in High-Grade Glioma: Does Low Molecular Weight Heparin Increase Intracranial Bleeding Risk?

BACKGROUND: Venous thromboembolism (VTE) occurs in up to 30% of patients with high-grade glioma (HGG). Concern for increased risk of intracranial hemorrhage (ICH) with therapeutic anticoagulation complicates VTE treatment. Some retrospective studies have reported an increased risk of ICH associated with therapeutic anticoagulation; however, effective alternatives to anticoagulation are lacking. The aim of our study is to assess the risk of ICH in HGG patients with VTE on low molecular weight heparin (LMWH).

METHODS: We performed a retrospective matched cohort study of HGG patients from 1/2005-8/2016. Blinded review of neuroimaging for ICH was performed. For analysis of the primary endpoint, estimates of cumulative incidence (CI) of ICH were calculated using competing risk analysis with death as competing risk; significance testing was performed using the Gray's test. Median survival was estimated using Kaplan-Meier method.

RESULTS: 220 patients were included, 88 (40%) with VTE treated with LMWH, 22 (10%) with VTE, not on anticoagulation (AC), and 110 (50%) without VTE. A total of 43 measurable ICH was recorded: 19 (26%) in LMWH, 3 (14%) in VTE not on AC, and 21 (19%) in non-VTE cohort. No significant difference was observed in the 1-year CI of ICH in the LMWH cohort and non-AC with VTE group (17% versus 9%; Gray's test, p=0.36). Among patients without VTE, the 1-year CI of ICH was 13%. Median survival was similar among all three cohorts.

CONCLUSIONS: Our data suggest that therapeutic LMWH is not associated with substantially increased risk of ICH in HGG patients.