Intracranial hemorrhage in patients with brain metastases treated with therapeutic enoxaparin: a matched cohort study

Jessica Donato, Federico Campigotto, Erik J. Uhlmann, Erika Coletti, Donna Neuberg, Griffin M. Weber and Jeffrey I. Zwicker

Key points

  • Significant intracranial hemorrhage occurs in 20-50% of patients with metastatic brain tumors.

  • Therapeutic anticoagulation in patients with brain metastasis did not increase the risk of intracranial hemorrhage.


Venous thromboembolism occurs frequently in cancer patients with brain metastases but there is limited evidence supporting the safety of therapeutic anticoagulation. To assess the risk of intracranial hemorrhage associated with the administration of therapeutic doses of low molecular heparin, we performed a matched, retrospective cohort study of 293 cancer patients with brain metastasis (104 with therapeutic enoxaparin and 189 controls). A blinded review of radiographic imaging was performed and intracranial hemorrhages were categorized as trace, measurable, and significant. There were no differences observed in the cumulative incidence of intracranial hemorrhage at 1 year in the enoxaparin and control cohorts for measurable (19% vs 21%, Gray test P=0.97, HR 1.02 [90%CI 0.66-1.59]), significant (21% vs 22%, P=0.87), and total (44% vs 37%, P=0.13) intracranial hemorrhages. The risk of intracranial hemorrhage was fourfold higher (adjusted HR 3.98, 90% CI 2.41-6.57, P<0.001) in patients with melanoma or renal cell carcinoma (N=60) than lung cancer (N=153), but the risk was not influenced by the administration of enoxaparin. Overall survival was similar for the enoxaparin and control cohorts (8.4 vs 9.7 months, Log-rank P=0.65). We conclude that intracranial hemorrhage is frequently observed in patients with brain metastases but that therapeutic anticoagulation does not increase the risk of intracranial hemorrhage.

  • Submitted February 4, 2015.
  • Accepted April 20, 2015.