Intracranial hemorrhage in setting of glioblastoma with venous thromboembolism

Abstract

Background: Venous thromboembolism (VTE) is a complication of glioblastoma. Anticoagulating patients with glioblastoma carries a theoretical risk of intracranial hemorrhage (ICH).

Methods: We performed a retrospective cohort study of consecutive glioblastoma patients (2007-2013) diagnosed with VTE.

Results: The study population comprised of 523 glioblastoma patients of whom 173 (33%) had VTE events. Seventeen (10%) had ICH: 6 (35%) subdural hematomas and 11 (65%) intratumoral hemorrhages. In total, 4 patients with ICH required neurosurgical intervention. Enhancement in the area of subsequent intratumoral hemorrhage was noted in 9 of 10 with available pre-ICH scans. Multivariable regression did not show associations between ICH and tumor enhancement diameter or use of vascular-endothelial-growth-factor inhibitor. Fifteen (16%) patients receiving anticoagulation had ICH compared with 2 (2.6%) not receiving anticoagulation (P = .005). The method of anticoagulation was not associated with development of ICH. Median survival times from nondistal VTE diagnosis to death were 8.0 and 3.5 months (P = .05) in patients receiving anticoagulation and those not on anticoagulation, respectively.

Conclusion: Patients with glioblastoma and VTE on anticoagulation have increased incidence of ICH. However, development of ICH was not associated with lower median survival from time of VTE. Intratumoral hemorrhage occurred within the enhancing portion of tumor; however, no relationship was identified between the development of ICH and (i) the median diameter of enhancement or (ii) type of anticoagulant used. However, patients with absence of enhancing tumor did not have intratumoral bleed, suggesting gross total resection may limit this adverse outcome. It is appropriate to initiate anticoagulation in glioblastoma patients with VTEs.

Keywords: anticoagulation; glioblastoma; intracranial hemorrhage; search terms; venous thromboembolism.

Fig. 1.

Survival after VTE diagnosis. The median post-VTE survival for patients receiving anticoagulation (lightly shaded line) was 8.0 months compared with 3.5 months for those not receiving anticoagulation (darkly shaded line). Patients with only distal DVTs were excluded. Abbreviations: VTE, venous thromboembolism; DVT, deep venous thrombosis.

Fig. 2.

Hemorrhage within enhancing tumor component. (A) T1-weighted MRI with contrast of a patient treated with enoxaparin with a noncontrast CT head, (B) obtained 4 weeks later demonstrating hemorrhage within the enhancing tumor with intraventricular extension; (C) T1-weighted MRI with contrast of a patient on enoxaparin with a noncontrast CT head, (D) obtained ∼4 weeks later demonstrating hemorrhage within the enhancing tumo; (E) T1-weighted MRI with contrast of a patient on enoxaparin with MRI SWI, (F) obtained 4 weeks later demonstrating a hemorrhage within enhancing tumor extending into the rostral midbrain; (G) T1-weight MRI with contrast of a patient treated with warfarin with a non-contrast CT head, and (H) obtained 11 days later demonstrating hemorrhage within the enhancing tumor component. Abbreviation: SWI, susceptibility-weighted imaging.