The Identification of Hypercoagulable Markers in Patients with Malignant Gliomas and Venous Thromboembolism.

Introduction: Patients with malignant gliomas have a high incidence of thrombotic events. There is no definitive data on what specific factors induce or predict for this hypercoagulable state.

Aim: The purpose of this prospective study was to identify specific risk factors for venous thromboembolism (VTE) in patients with malignant gliomas by examining suspected procoagulant markers in their plasma.

Patients and Methods: Adult patients who presented for outpatient consultation to the neuro-oncology clinic at the Dana-Farber Cancer Institute from 9/4/2003 to 6/9/2005 with a pathologically documented diagnosis of malignant glioma were evaluated for study. Patients with a prior diagnosis of VTE or on current chemotherapy or anticoagulant therapy were excluded. Upon study entry and prior to the initiation of radiation therapy or chemotherapy, a single peripheral blood sample was collected. Citrated plasma was stored at −80°C until batch testing occurred. Tests for D-dimer, von Willebrand factor antigen, fibrinogen, factor VIII, plasminogen, lupus anticoagulant, thrombin-antithrombin, and prothrombin fragment 1+2 were performed at reference laboratories. All patients were prospectively followed for development of symptomatic VTE (confirmed by radiological testing). Of the twenty-nine patients on study, twenty-five died and four are still alive. Time to death, number of recurrences, and number of hospitalizations were collected to determine if there was an association between these events and presence of VTE.

Results: Twenty-nine patients who met criteria and had analyzable blood samples were included in study. The rate of symptomatic VTE was 24% and VTE occurred 1–13 months after entry onto the study. Development of VTE was associated with elevated levels of D-dimer [defined as greater than 500 mg/dL (p=0.0230)] and elevated levels of fibrinogen [defined as greater than 400% (p=0.0164)]. The median levels of D-dimer and fibrinogen were significantly greater in the patients who developed VTE compared to those who did not develop VTE (953 mg/dL v 481 mg/dL, p=0.0249 and 425% v 290%, p=0.0312, respectively). The number of hospitalizations was also significantly associated with the presence of VTE (p=0.0130). There was no association between the number of tumor recurrences/progressions or time to death and presence of VTE. All patients underwent surgery prior to study enrollment. There was no difference between the patients who developed VTE and those who did not in terms of timing of the surgery, presence of residual tumor, grade or type of tumor, or steroid use.

Conclusion: The incidence of symptomatic VTE in patients with malignant gliomas was 24%. Elevated levels of D-dimer and fibrinogen at initiation of therapy were associated with the development of VTE. These risk factors may help determine which patients are at increased risk of VTE and might benefit from prophylactic anticoagulation. These suggestive results need to be confirmed in a larger trial.