title: A prospective multicenter study of venous thromboembolism in patients with newly-diagnosed high-grade glioma: hazard rate and risk factors.
abstract: Venous thromboembolism (VTE) is a common complication in patients with high-grade gliomas. The purpose of this prospective multicenter study was to determine the hazard rate of first symptomatic VTE in newly-diagnosed glioma patients and identify clinical and laboratory risk factors. On enrollment, demographic and clinical information were recorded and a comprehensive coagulation evaluation was performed. Patients were followed until death. The study end point was objectively-documented symptomatic VTE. One hundred seven patients were enrolled with a median age of 57 years (range 29-85) between June 2005 and April 2008. Ninety-one (85 %) had glioblastoma multiforme (GBM). During an average survival of 17.7 months, 26 patients (24 %) (95 % CI 17-34 %) developed VTE (hazard rate 0.15 per person-year) and 94 patients (88 %) died. Median time to VTE was 14.2 weeks post-operation (range 3-126). Patients with an initial tumor biopsy were 3.0 fold more likely to suffer VTE (p = 0.02). Patients with an elevated factor VIII activity (>147 %) were 2.1-fold more likely to develop VTE. ABO blood group, D dimer and thrombin generation were not associated with VTE. No fatal VTE occurred. VTE is a common complication in patients with newly-diagnosed high grade gliomas, particularly in the first six months after diagnosis. Patients with an initial tumor biopsy and elevated factor VIII levels are at increased risk. However, VTE was not judged to be primarily responsible for any patient deaths. Therefore, outpatient primary VTE prophylaxis remains investigational until more effective primary prophylaxis strategies and therapies for glioma are identified.
authors.affiliation: Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 7300, Baltimore, MD, 21205, USA. mstreif@jhmi.edu.|Division of Hematology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. mstreif@jhmi.edu.|Armstrong Institute of Patient Safety and Quality, Johns Hopkins Medical Institutions, Baltimore, MD, USA. mstreif@jhmi.edu.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Streiff
authors.affiliation: Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.|Brain Cancer Program, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
authors.forename: Xiaobu
authors.initials: X
authors.lastname: Ye
authors.affiliation: Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 7300, Baltimore, MD, 21205, USA.|Division of Hematology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Kickler
authors.affiliation: Brain Cancer Program, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
authors.forename: Serena
authors.initials: S
authors.lastname: Desideri
authors.affiliation: Special Coagulation Laboratory, The Johns Hopkins Hospital, Baltimore, MD, 21205, USA.
authors.forename: Jayesh
authors.initials: J
authors.lastname: Jani
authors.affiliation: Brain Cancer Program, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
authors.forename: Joy
authors.initials: J
authors.lastname: Fisher
authors.affiliation: Brain Cancer Program, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Grossman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005910:Glioma / Q000453:epidemiology* / Q000473:pathology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000453:epidemiology*
keywords: Cancer; Factor VIII; Glioblastoma; Glioma; Risk factors; Venous thromboembolism