Incidence and determinants of thrombotic and bleeding complications in patients with glioblastoma

Abstract

Background Glioblastoma patients are considered to be at high risk of venous thromboembolism (VTE) and major bleeding (MB), although reliable incidence estimates are lacking. Moreover, the risk of arterial thromboembolism (ATE) in these patients is largely unknown. Our aim was to assess the cumulative incidence, predictors, and prognostic impact of VTE, ATE, and MB on subsequent complications and mortality. Methods Cohort study of 967 consecutive patients diagnosed with glioblastoma between 2004–2020 in two hospitals. Patients were followed from 6 months before date of histopathological glioblastoma diagnosis up to 2 years after, or until an outcome of interest (VTE, ATE, and MB) or death occurred, depending on the analysis. Cumulative incidences were estimated with death as competing risk. Cox regression was used to identify predictors and the prognostic impact. Results A total of 101 patients were diagnosed with VTE, 50 with ATE, and 126 with MB during a median follow‐up of 15 months (interquartile range 9.0–22). The adjusted 1‐year cumulative incidence of VTE was 7.5% (95% confidence interval [CI] 5.9–9.3), of ATE 4.1% (95% CI 3.0–5.6), and of MB 12% (95% CI 9.6–14). Older age, type of surgery, and performance status were predictors of VTE. Incident VTE during follow‐up was associated with MB (adjusted HR 4.7, 95% CI 2.5–9.0). MB and VTE were associated with mortality (adjusted HR 1.7, 95% CI 1.3–2.1 and 1.3, 95% CI 1.0–1.7, respectively). Conclusion We found considerable incidences of VTE and MB in glioblastoma patients, with both complications associated with poorer prognosis. Our observations emphasize the need for prospective studies to determine optimal thromboprophylaxis and VTE treatment strategy in these patients.

External validation and updating of prediction models of bleeding risk in patients with cancer receiving anticoagulants

“…Invasive procedures such as surgery, intravenous access lines and biopsies also carry an increased bleeding risk, notably in anticoagulated patients 2. Finally, the malignant tumour itself may also cause spontaneous bleeding, for example, gastrointestinal, lung or brain tumours 3–5. Hence, even though often clearly indicated, anticoagulant therapy in patients with cancer with VTE or AF is a complicated clinical endeavour, notably during certain periods of the disease, warranting constantly a vigorous balance between bleeding and thrombosis risk.…”

Incidence of venous thromboembolism and bleeding in patients with malignant central nervous system neoplasm: Systematic review and meta-analysis

“…This finding may be attributed to the shorter exposure time of these patients to the risk of a VTE. Kaptein et al [ 27 ] showed that the median recurrence among GBM was nearly 8 months, varying between 4.8 months and one year. In newly diagnosed HGG patients, Thaler et al [ 61 ] showed that the probability of having a VTE ranged between 3.3 and almost 40% when considering cancer-related factors (e.g., leukocyte and platelet count, P-selectin, prothrombin-fragment 1 + 2, FVIII activity, and D-dimer).…”

A novel classifier combining G protein-coupled receptors and the tumor microenvironment is associated with survival status in glioblastoma

“…Additionally, TNFα is thought to be a triggering factor in thrombus formation via activation of the complement system ( Page et al, 2018 ). It might be proposed that increased TNFα in macrophage contributes to the thrombus in glioma ( Czap et al, 2019 ; Kaptein et al, 2022 ). However, the intricate relationship between GPCR, TNF, and coagulation in glioma requires further investigation in future studies.…”