title: Safety of concurrent bevacizumab therapy and anticoagulation in glioma patients.
abstract: Venous thromboembolic events (VTE) are common in glioma patients and are typically treated with anticoagulant medications. The anti-angiogenic agent bevacizumab (BVZ) increases the risks of both VTE and hemorrhagic complications. Little is known about the hemorrhagic risk of anticoagulation in glioma patients receiving BVZ. We reviewed medical records from 282 BVZ-treated patients at our center and identified 64 who received concurrent anticoagulant therapy. The risk and severity of hemorrhagic complications were assessed. Fisher's exact test was used to compare the risk of hemorrhage between subjects who received and did not receive anticoagulants. Forty-seven patients (73%) had glioblastoma, 15 (23%) anaplastic glioma, and 2 (3%) other tumors. Thirteen (20%) and 51 (80%) patients received warfarin and low-molecular-weight heparin, respectively. The indication for anticoagulation was deep venous thrombosis in 37 patients (58%), pulmonary embolism in 22 (34%), and both in 5 (8%). Thirteen patients (20%) experienced hemorrhage, of which four hemorrhages (6%) were serious (grade ≥ 3): one patient had grade 5 intracerebral hemorrhage (ICH), one grade 4 ICH, one grade 3 epistaxis, and one grade 3 gastrointestinal hemorrhage. ICH was seen in seven patients (11%), of which five (8%) were grade 1. Among 218 patients who did not receive anticoagulants, there were two (1%) serious hemorrhages (both grade 4 ICH). Both the serious hemorrhage rate and overall ICH rate were higher in patients who received anticoagulants (P = 0.03 and 0.02, respectively). Anticoagulant use during BVZ therapy may increase the risk of hemorrhage in glioma patients, although it is generally well tolerated.
authors.affiliation: Center for Neuro-Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Norden
authors.forename: Julia
authors.initials: J
authors.lastname: Bartolomeo
authors.forename: Shota
authors.initials: S
authors.lastname: Tanaka
authors.forename: Jan
authors.initials: J
authors.lastname: Drappatz
authors.forename: Abigail S
authors.initials: AS
authors.lastname: Ciampa
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Doherty
authors.forename: Debra C
authors.initials: DC
authors.lastname: Lafrankie
authors.forename: Sandra
authors.initials: S
authors.lastname: Ruland
authors.forename: Eudocia C
authors.initials: EC
authors.lastname: Quant
authors.forename: Rameen
authors.initials: R
authors.lastname: Beroukhim
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use*; D000925:Anticoagulants / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000150:complications* / Q000188:drug therapy; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000188:drug therapy; D003131:Combined Modality Therapy; D005260:Female; D005910:Glioma / Q000150:complications* / Q000188:drug therapy; D006470:Hemorrhage / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011655:Pulmonary Embolism / Q000188:drug therapy; D012189:Retrospective Studies; D012306:Risk
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000925:Anticoagulants; D000068258:Bevacizumab