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Blood. 2015 Jul 23;126(4):494-9. doi: 10.1182/blood-2015-02-626788. Epub 2015 May 18.

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

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Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA;
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA; and.
Department of Neurology.
Division of Hemostasis and Thrombosis, Division of Hematology and Oncology, and.
Interdisciplinary Medicine and Biotechnology, Center for Biomedical Informatics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.


Venous thromboembolism occurs frequently in patients with cancer who have brain metastases, but there is limited evidence supporting the safety of therapeutic anticoagulation. To assess the risk for intracranial hemorrhage associated with the administration of therapeutic doses of low-molecular-weight heparin, we performed a matched, retrospective cohort study of 293 patients with cancer with brain metastases (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 = .97; hazard ratio, 1.02; 90% confidence interval [CI], 0.66-1.59), significant (21% vs 22%; P = .87), and total (44% vs 37%; P = .13) intracranial hemorrhages. The risk for intracranial hemorrhage was fourfold higher (adjusted hazard ratio, 3.98; 90% CI, 2.41-6.57; P < .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 = .65). We conclude that intracranial hemorrhage is frequently observed in patients with brain metastases, but that therapeutic anticoagulation does not increase the risk for intracranial hemorrhage.

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