Intracranial hemorrhage with direct oral anticoagulants in patients with brain tumors

J Thromb Haemost. 2019 Jan;17(1):72-76. doi: 10.1111/jth.14336. Epub 2018 Dec 11.


Essentials Intracranial hemorrhage (ICH) is common in patients with brain tumors. We compared rates of ICH with DOACs and low molecular weight heparin. DOACs were associated with a lower incidence of ICH in primary brain tumors. DOACs appear safe to administer to patients with brain tumors. SUMMARY: Background Direct oral anticoagulants (DOACs) are efficacious in the treatment of cancer-associated thrombosis but are associated with an increased risk of hemorrhage compared with low-molecular-weight heparin in certain malignancies. Whether the DOACs increase the incidence of intracranial hemorrhage (ICH) in patients with brain tumors is not established. Objectives To determine the cumulative incidence of ICH in DOACs compared with Low-molecular-weight heparin (LMWH) in patients with brain tumors and venous thromboembolism. Patients and methods A retrospective comparative cohort study was performed. Radiographic images for all ICH events were reviewed and the primary endpoint was cumulative incidence of ICH at 12 months following initiation of anticoagulation. Results and conclusions A total of 172 patients with brain tumors were evaluated (42 DOAC and 131 LMWH). In the primary brain tumor cohort (n = 67), the cumulative incidence of any ICH was 0% in patients receiving DOACs vs. 36.8% (95% confidence interval [CI], 22.3-51.3%) in those treated with LMWH, with a major ICH incidence of 18.2% (95% CI, 8.4-31.0). In the brain metastases cohort (n = 105), DOACs did not increase the risk of any ICH relative to enoxaparin, with an incidence of 27.8% (95% CI, 5.5-56.7%) compared with 52.9% (95% CI, 37.4-66.2%). Similarly, DOAC did not increase the incidence of major ICH in brain metastases, with a cumulative incidence 11.1% (95% CI, 0.5-40.6%) vs. 17.8% (95% CI, 10.2-27.2%). We conclude that DOACs are not associated with an increased incidence of ICH relative to LMWH in patients with brain metastases or primary brain tumors.

Keywords: brain tumors; direct oral anticoagulants; intracranial hemorrhage; low-molecular-weight heparin; venous thromboembolism.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects*
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / epidemiology*
  • Female
  • Heparin, Low-Molecular-Weight / administration & dosage
  • Heparin, Low-Molecular-Weight / adverse effects*
  • Humans
  • Incidence
  • Intracranial Hemorrhages / chemically induced*
  • Intracranial Hemorrhages / diagnostic imaging
  • Intracranial Hemorrhages / epidemiology*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / drug therapy*
  • Venous Thromboembolism / epidemiology


  • Anticoagulants
  • Heparin, Low-Molecular-Weight