Safety of anticoagulation use and bevacizumab in patients with glioma

Abstract

Bevacizumab in combination with chemotherapy is now being studied for the treatment of malignant gliomas. However, the risk of intracranial hemorrhage has limited its use in patients requiring full anticoagulation for venous thrombosis. To assess the safety of using anticoagulation with bevacizumab, we conducted a retrospective review of our patients who were treated with bevacizumab while receiving anticoagulation. We reviewed their medical records and imaging for signs of hemorrhage. In total, we had 21 patients who received anticoagulation and bevacizumab concurrently for a median time of 72 days. Eighteen patients had adequate anticoagulation for venous thrombosis. There were no frank lobar hemorrhages in any patient. Three patients had small, intraparenchymal hemorrhages on MRI, but only one patient actually developed symptoms due to the hemorrhage. None of these patients had residual neurological deficits from the hemorrhages. Two more patients had evidence of a minor increase in signal on noncontrast T1-weighted sequence, presumed to be petechial hemorrhages, without any clinical sequelae or progression. In contrast, seven patients who had symptomatic hemorrhages from bevacizumab were not on any anticoagulation. In this retrospective review, anticoagulation did not lead to any major hemorrhages and does not appear to be a contraindication for starting bevacizumab therapy.

Fig. 1

Noncontrast T1-weighted MRI of three patients who developed intraparenchymal hemorrhages while on anticoagulation and bevacizumab. (A – C) Images for patient 1 were obtained prior to treatment (A), 39 days later at the time of symptoms from hemorrhage (B), and 2 months later on follow-up, while still on bevacizumab (C). (D – F) Images of patient 2 were obtained before treatment (D), at 1 month before hemorrhage (E), and at the time of hemorrhage (F). (G – I) Images for patient 3 were obtained prior to (G), 2 months after (H), and 6 months after (I) starting both anticoagulation and bevacizumab.

Fig. 2

Noncontrast T1-weighted MRI (A – C) and noncontrast head CT (D and E) from two patients with petechial hemorrhages while on anticoagulation and bevacizumab. (A – C) Patient 4 initial scan (A), 1 month after (B), and 4 months after (C) being on both treatments. (D and E) Patient 5 images obtained before (D) and 4 months after (E) both treatments had started.

Fig. 3

Representative imaging from patients 1, 4, and 5 with major hemorrhages but not on anticoagulation. (A and B) Patient 1 non-contrast T1-weighted MRIs before bevacizumab (A) and 1 month after (B). (C and D) Noncontrast T1-weighted MRIs for patient 4 obtained before treatment (C) and almost 5 months later (D). (E and F) Images for patient 5 were obtained from before (E) and 3 months after (F) bevacizumab.