Prothrombotic state in glioblastoma multiforme: an evaluation of the procoagulant activity of circulating microparticles

Abstract

The relationship between venous thromboembolism (VTE) and cancer is supported by several pathogenetic factors, including circulating microparticles (MP) originating from different cells and often bearing tissue factor. Since VTE often complicates the clinical course of patients with glioblastoma multiforme (GBM; WHO grade IV astrocytoma) and the role of MPs in these patients population is still not clear, this prospective study was conducted to evaluate the procoagulant activity of circulating MP (MP activity) in GBM patients. We enrolled 61 GBM patients undergoing gross-total or subtotal surgical resection followed by combined radio-chemotherapy; 20 healthy volunteers were tested as controls. Blood samples for MP activity and hemostatic profiles were obtained before and then 1 week and 1, 4, and 7 months after surgery. GBM patients had significantly higher mean MP activity levels than healthy controls before and 7 days after surgery. During the follow-up, MP activity levels became significantly lower 1 and 4 months after surgery (P = 0.007 and P = 0.018, respectively) than prior to surgery, but this decrease was only seen in the subgroup achieving complete tumor resection. MP activity levels increased in 7 (63.6%) of 11 patients who developed VTE. The different incidence of the increase in MP activity levels between patients with and without VTE was statistically significant (χ (2) = 4.93, P = 0.026; relative risk 1.38, 95% CI 1.03-1.86). GBM patients may have an increase in MP-associated procoagulant activity that could contribute to any prothrombotic states and increases the likelihood of VTE complications; this procoagulant activity drops during control of disease.

Extracellular vesicles and intercellular communication within the nervous system

“…106, 107, and Figure 3). GBMs are also associated with a peripheral coagulopathy (108), which is mediated by microparticles (EVs) released from the tumors that contain high levels of tissue factor and initiate thrombin formation (109,110).…”

Venous Thromboembolism in Brain Tumor Patients: A Review of Literature

“…In 2011, Sartori et al studied the procoagulant activity of circulating MPs in patients harboring glioblastoma multiforme (GBM). They found that MP activity levels increased in 63.6% of 61 patients who underwent resection of GBM, a statistically significant association (chi2=4.93, p=0.026) [62]. In 2004, Browd et al demonstrated that DVT formation in patients undergoing neurosurgery has been reported as high as 25%, with mortality rates from PE ranging from 9 to 50% [63].…”

“…Not all cancers produce these procoagulant effects equally, however, which leads to the disparity in VTE rate between tumors of the brain and cancers of other sites. For example, studies have shown that high-grade tumors of the brain result in a higher concentration of TF, with an associated higher rate of VTE development [62]. A study of 1000 patients undergoing operations for brain tumors showed a strong correlation between higher tumor grade and DVT development ( …”

Spitting out the demons: Extracellular vesicles in glioblastoma

“…For instance, thromboembolic diseases observed in GBM patients might rely on the pro-coagulant activity detected in circulating microparticles. 39,40 Circulating EVs were shown to transport pro-permeability and pro-angiogenic factors, 10,21 including GSC-derived semaphorin 3A that could reach the endothelium of virtually all healthy organs. 21 Indeed, GBM patient serum-purified EVs are loaded with semaphorin 3A, which further orchestrated the loss of barrier integrity.…”