To assess intracerebral hemorrhage (ICH) risk with direct oral anticoagulants (DOAC) versus low molecular weight heparin (LMWH) in patients with primary brain tumors (PBT).

Long-term anticoagulation is common in PBT patients for many indications, including arrhythmias and venous thromboembolism (VTE).  Large phase 3 trials have demonstrated DOAC safety in VTE treatment for cancer patients generally, but safety data in PBT is limited. Early data suggests that DOACs are safe in PBT patients, but the rates and severity of intracerebral hemorrhage (ICH) are not well characterized, particularly for low-grade gliomas. 

Adult patients with glioma who received LMWH and/or DOAC for at least 10 days between Jan 1, 2008 - Jan 1, 2023 were reviewed. ICH rates and severity in patients receiving DOAC or LMWH were examined.

Of the 304 patients included, 174 received DOAC and 157 received LMWH for at least 10 days (27 transitioned between LMWH and DOAC). 34% (103) had VTE within six months before or after PBT diagnosis, at a median of 43 days following diagnosis. Of the patients with VTE within 6 months of diagnosis, 76% (78) were diagnosed with glioblastoma. 

ICH rates were not significantly different among patients on apixaban vs. LMWH (2.83% vs. 1.91%, p = 0.95) or rivaroxaban vs. LMWH (1.35% vs. 1.91%, p = 1.0). Most (57%) ICH was trace or minor, 14% (1) was subdural, and 29% (2) was major or fatal. Of the major or fatal ICH, 0 occurred on DOAC and 2 on LMWH. 71% of patients with ICH within 6 months before or after PBT diagnosis had glioblastoma. 

This retrospective study suggests that DOACs are relatively safe in PBT patients, with a similar risk of ICH to LMWH. Prospective studies are needed to definitively establish the risk of anticoagulation in this population.