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 pri-marily responsible for any patient deaths. Therefore, out-patient primary VTE prophylaxis remains investigational until more effective primary prophylaxis strategies and therapies for glioma are identified.

Venous Thromboembolism in Brain Tumors: Risk Factors, Molecular Mechanisms, and Clinical Challenges

“…However, the association between ABO blood group and VTE risk in brain tumors could not be confirmed in a subsequent prospective study by the same authors. 17 The brain tumor subtype, with highest risks in glioblastoma, 3,12 a larger tumor size, 3,11 and presence of intratumoral thrombi have been described as tumor-related risk factors for VTE. 4,18 In 2016, Unruh et al described a very low risk of VTE in patients with gliomas harboring the isocitrate dehydrogenase 1 (IDH1) mutation.…”

“…The risk is also higher in patients undergoing tumor biopsy than in those undergoing surgery for tumor resection. 17 The risk ranges between 3 and 60% in the first 6 weeks after surgery, depending on the prophylaxis regimen, methods of diagnosis, and the reporting studies. 3 In an analysis of 7376 patients with primary malignant brain tumors who underwent craniotomy for tumor surgery, 3.5% of patients developed VTE within 30 days after surgery.…”

Thromboprophylaxis in Cancer Patients Undergoing Surgery

“…Neurosurgical patients carry a substantial risk of developing VTE, especially in those with malignant gliomas, ranging from 17 to 26%. 26 Postoperative VTE risk was reported in up to 60% of patients who had craniotomy for brain neoplasm and continued to be as high as 23% at 1 year after surgery in one study (►Table 1). 27 The risk of intracranial hemorrhage (ICH) is the major issue in these patients, even without surgery.…”

Venous thromboembolism prophylaxis in cancer patients — guidelines focus on surgical patients

“…Venous thromboembolism is one of the most significant complications in the population of the neurosurgical cancer patients and its prevalence is related to the type of performed surgery, perioperative immobilization and the tumor itself [14,[146][147][148][149]. Both, intra-cranial surgery and a malignant tumor presence significantly increase the risk of local bleeding complications [14,150,151].…”