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

  • Clinical Study – Patient Study
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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.

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References

  1. Wun T, White RH (2009) Venous thromboembolism (VTE) in patients with cancer: epidemiology and risk factors. Cancer Invest 27:63–74

    Article  PubMed  Google Scholar 

  2. Khorana AA (2010) Venous thromboembolism and prognosis in cancer. Thromb Res 125:490–493

    Article  PubMed  CAS  Google Scholar 

  3. Falanga A (2009) The incidence and risk of venous thromboembolism associated with cancer and nonsurgical cancer treatment. Cancer Invest 27:105–115

    Article  PubMed  CAS  Google Scholar 

  4. Milsom C, Rak J (2007) Tissue factor and cancer. Pathophysiol Haemost Thromb 36:160–176

    Article  CAS  Google Scholar 

  5. Zhang J, Ding J, Zhang X, Shao X, Hao Z (2005) Regulation of vascular endothelial growth factor production and angiogenesis by tissue factor in SGC-7901 gastric cancer cells. Cancer Biol Ther 4:769–772

    Article  PubMed  CAS  Google Scholar 

  6. Zwicker JI, Furie BC, Furie B (2007) Cancer-associated thrombosis. Crit Rev Oncol Hematol 62:126–136

    Article  PubMed  Google Scholar 

  7. Aharon A, Brenner B (2009) Microparticles, thrombosis and cancer. Best Pract Res Clin Haematol 22:61–69

    Article  PubMed  CAS  Google Scholar 

  8. Davizon P, Lòpez JA (2009) Microparticles and thrombotic disease. Curr Opin Hematol 16:334–341

    Article  PubMed  Google Scholar 

  9. CBTRUS (2009) 2009–2010 CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in eighteen states in 2002–2006. Central Brain Tumor Registry of the United States, Hinsdale, IL. www.cbtrus.org

  10. Stupp R, Hegi ME, Mason WP et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466

    Article  PubMed  CAS  Google Scholar 

  11. Marras LC, Geerts WH, Perry JR (2000) The risk of venous thromboembolism is increased throughout the course of malignant glioma. Cancer 89:640–646

    Article  PubMed  CAS  Google Scholar 

  12. Semrad JT, O’Donnel R, Wun T et al (2007) Epidemiology of venous thromboembolism in 9489 patients with malignant glioma. J Neurosurg 106:601–608

    Article  PubMed  Google Scholar 

  13. Franchini M, Montagnana M, Targher G, Manzato F, Lippi G (2007) Pathogenesis, clinical and laboratory aspects of thrombosis in cancer. J Thromb Thrombolysis 24:29–38

    Article  PubMed  Google Scholar 

  14. Colin C, Voutsinos-Porche B, Nanni I et al (2009) High expression of cathepsin B and plasminogen activator inhibitor type-1 are strong predictors of survival in glioblastomas. Acta Neuropathol 118:745–754

    Article  PubMed  CAS  Google Scholar 

  15. Rong Y, Belozerov VE, Tucker-Burden C et al (2009) Epidermal growth factor receptor and PTEN modulate tissue factor expression in glioblastoma through JunD/activator protein 1 transcriptional activity. Cancer Res 69:2540–2549

    Article  PubMed  CAS  Google Scholar 

  16. Wells PS, Anderson DR, Bormanis J et al (1997) Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 350:1795–1798

    Article  PubMed  CAS  Google Scholar 

  17. Wells PS, Anderson DR, Rodger M et al (2000) Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost 83:416–420

    PubMed  CAS  Google Scholar 

  18. Simanek R, Vormittag R, Hassler M et al (2007) Venous thromboembolism and survival in patients with high-grade glioma. Neuro Oncol 9:89–95

    Article  PubMed  Google Scholar 

  19. Rodas RA, Fenstermaker RA, McKeever PE et al (1998) Correlation of intraluminal thrombosis in brain tumor vessels with postoperative thrombotic complications: a preliminary report. J Neurosurg 89:200–205

    Article  PubMed  CAS  Google Scholar 

  20. Walsh DC, Kakkar AK (2001) Thromboembolism in brain tumors. Curr Opin Pulm Med 7:326–331

    Article  PubMed  CAS  Google Scholar 

  21. Zwicker JI, Liebman HA, Neuberg D et al (2009) Tumor-derived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy. Clin Cancer Res 15:6830–6840

    Article  PubMed  CAS  Google Scholar 

  22. Tesselaar ME, Romijn FP, Van Der Linden IK, Prins FA, Bertina RM, Osanto S (2007) Microparticle-associated tissue factor activity: a link between cancer and thrombosis? J Thromb Haemost 5:520–527

    Article  PubMed  CAS  Google Scholar 

  23. Hron G, Kollars M, Weber H et al (2007) Tissue factor-positive microparticles: cellular origin and association with coagulation activation in patients with colorectal cancer. Thromb Haemost 97:119–123

    PubMed  CAS  Google Scholar 

  24. Skog J, Wurdinger T, van Rijn S et al (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10:1470–1476

    Article  PubMed  CAS  Google Scholar 

  25. Tesselaar ME, Romijn FP, van der Linden IK, Bertina RM, Osanto S (2009) Microparticle associated tissue factor activity in cancer patients with and without thrombosis. J Thromb Haemost 7:1421–1423

    Article  PubMed  CAS  Google Scholar 

  26. Manly DA, Wang J, Glover SL et al (2010) Increased microparticle tissue factor activity in cancer patients with venous thromboembolism. Thromb Res 125:511–512

    Article  PubMed  CAS  Google Scholar 

  27. Khorana AA, Francis CW, Menzies KE et al (2008) Plasma tissue factor may be predictive of venous thromboembolism in pancreatic cancer. J Thromb Haemost 6:1983–1985

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiologic, Thoracic and Vascular Sciences, Padua University Hospital, Via Giustiniani 2, 35128, Padova, Italy

    Maria Teresa Sartori, Andrea Ballin, Graziella Saggiorato & Giuseppe Cella

  2. Department of Neurosurgery, Padua University Hospital, Padua, Italy

    Alessandro Della Puppa, Renato Scienza & Domenico d’Avella

  3. Department of Laboratory Medicine, Padua University Hospital, Padua, Italy

    Daniela Bernardi & Andrea Padoan

Authors
  1. Maria Teresa Sartori
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  2. Alessandro Della Puppa
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  3. Andrea Ballin
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  4. Graziella Saggiorato
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  5. Daniela Bernardi
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  6. Andrea Padoan
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  7. Renato Scienza
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  8. Domenico d’Avella
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  9. Giuseppe Cella
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Correspondence to Maria Teresa Sartori.

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Sartori, M.T., Della Puppa, A., Ballin, A. et al. Prothrombotic state in glioblastoma multiforme: an evaluation of the procoagulant activity of circulating microparticles. J Neurooncol 104, 225–231 (2011). https://doi.org/10.1007/s11060-010-0462-8

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  • DOI: https://doi.org/10.1007/s11060-010-0462-8

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