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

• Published in: Blood Vol. 126; no. 4; pp. 494 - 499
• Main Authors: Donato, Jessica, Campigotto, Federico, Uhlmann, Erik J., Coletti, Erika, Neuberg, Donna, Weber, Griffin M., Zwicker, Jeffrey I.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23-07-2015; American Society of Hematology
• Subjects: Adult; Aged; Aged, 80 and over; Anticoagulants - adverse effects; Boston - epidemiology; Brain Neoplasms - complications; Brain Neoplasms - mortality; Brain Neoplasms - secondary; Case-Control Studies; Clinical Trials and Observations; Enoxaparin - adverse effects; Female; Follow-Up Studies; Humans; Incidence; Intracranial Hemorrhages - chemically induced; Intracranial Hemorrhages - epidemiology; Intracranial Hemorrhages - mortality; Male; Middle Aged; Neoplasm Staging; Neoplasms - drug therapy; Neoplasms - mortality; Neoplasms - pathology; Prognosis; Retrospective Studies; Risk Factors; Survival Rate; Venous Thromboembolism - drug therapy; Venous Thromboembolism - etiology; Venous Thromboembolism - mortality; Young Adult; Boston
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2015-02-626788

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.
•Significant intracranial hemorrhage occurs in 20% to 50% of patients with metastatic brain tumors.•Therapeutic anticoagulation in patients with brain metastasis did not increase the risk for intracranial hemorrhage.