Circulating microparticles of glial origin and tissue factor bearing in high-grade glioma: a potential prothrombotic role

Thromb Haemost. 2013 Aug;110(2):378-85. doi: 10.1160/TH12-12-0957. Epub 2013 Jun 27.

Abstract

Venous thromboembolism (VTE) may complicate the clinical course of glioblastoma multiforme (GBM). Circulating microparticles (MPs) have been associated with cancer-related VTE. Sixty-one consecutive patients with GBM undergoing gross-total (41) or subtotal (20) surgical resection followed by radio-chemotherapy were prospectively evaluated. MPs numbers according to cellular origin and the procoagulant activity of annexin V positive (AV+) MPs (MP-activity) were measured before surgery and then 1 week and 1, 4, and 7 months after surgery. Glial (GFAP+) and endothelial (CD62E+) derived MPs, AV+ and tissue factor-bearing (TF+) MPs were measured using flow cytometry. Baseline levels of GFAP+/TF-, TF+/GFAP-, and GFAP+/TF+ MPs were significantly higher in GBM patients than in healthy controls, and significantly increased at each time point after surgery; at 7 months, a further significant increase over the level found a week after surgery was only seen in the subtotally resected patients. The number AV+/CD62E- MPs increased in GBM patients and correlated with MP activity. TF+/GFAP- MPs numbers were significantly higher in 11 GBM patients who developed VTE than in those who did not (p 0.04). TF+/GFAP- MPs levels above the 90th percentile (calculated in GBM patients without VTE) were associated with a higher risk of VTE (RR 4.17, 95% CI 1.57-11.03). In conclusion, the numbers of glial-derived and/or TF-bearing MPs were high in GBM patients both before and even more after the neoplasm was treated, especially in patients with subtotal resection likely according to disease progression. A contribution of TF+/GFAP- MPs to the risk of VTE is suggested.

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms / blood*
  • Brain Neoplasms / complications*
  • Case-Control Studies
  • Cell-Derived Microparticles / metabolism
  • Cell-Derived Microparticles / pathology*
  • E-Selectin / blood
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Female
  • Glial Fibrillary Acidic Protein / blood
  • Glioblastoma / blood*
  • Glioblastoma / complications*
  • Humans
  • Male
  • Middle Aged
  • Neuroglia / pathology
  • Risk Factors
  • Thromboplastin / metabolism*
  • Venous Thromboembolism / blood*
  • Venous Thromboembolism / etiology*

Substances

  • E-Selectin
  • Glial Fibrillary Acidic Protein
  • Thromboplastin