Skip to main content

Advertisement

Log in

Predictors of Venous Thromboembolism in Patients with Glioblastoma

  • Original Article
  • Published:
Pathology & Oncology Research

Abstract

To evaluate different risk factors associated with development of venous thromboembolism (VTE) in patients with Glioblastoma (GBM). A retrospective chart review was performed to include patients diagnosed with GBM from 2001 to 2011. Cases (n = 162) were defined as patients with GBM who developed VTE after diagnosis of GBM. Controls (n = 840) were defined as patients with GBM with no history of VTE. Data was collected for multiple variables including age, gender, race, length of hospital stay after brain biopsy, total number of hospital admissions unrelated to VTE, Karnofsky Performance Status (KPS), use of Bevacizumab and any bleeding episodes. Patients with GBM who had VTE had poorer KPS scores, with the majority (57 %) being in between 40 and 70, as compared to the controls where majority (82 %) had better performance (KPS 80-100). For every one year increase in age, the odds of developing VTE increased by 3 % (OR 1.03, 95%CI 1.02-1.04, p < 0.001) with the mean age being 61.8 ± 11.4 years. GBM patients who developed a VTE were found to have greater number of hospital admissions (OR 1.43, 95%CI 1.33-1.53, p < 0.001) and longer stays in hospital after GBM biopsy (OR 1.14, 95%CI 1.09-1.18, p < 0.001). Patients receiving Bevacizumab were more likely to develop VTE (OR 1.79, 95%CI 1.21-2.64, p < 0.001) and were more likely to have a bleed (OR 3.78, 95 % CI 2.70-5.30, p < 0.001). Patients with GBM are at a higher risk of developing VTE. The risk is higher in older patients who require multiple hospital admissions, longer duration of hospital stays related to GBM biopsy, and in patients with lower KPS scores. Bevacizumab use is related to a higher incidence of VTE as well as bleeds. This study suggests that a more aggressive strategy for VTE prophylaxis should be considered in GBM patients with risk factors for VTE.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Thaler J, Ay C, Kaider A, Reitter EM, Haselbock J, Mannhalter C, Zielinski C, Marosi C, Pabinger I (2014) Biomarkers predictive of venous thromboembolism in patients with newly diagnosed high-grade gliomas. Neuro-Oncology 16(12):1645–1651. doi:10.1093/neuonc/nou106

    Article  PubMed  PubMed Central  Google Scholar 

  2. Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH (2007) Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 5(3):632–634. doi:10.1111/j.1538-7836.2007.02374.x

    Article  CAS  PubMed  Google Scholar 

  3. Magnus N, D'Asti E, Garnier D, Meehan B, Rak J (2013) Brain neoplasms and coagulation. Semin Thromb Hemost 39(8):881–895. doi:10.1055/s-0033-1357483

    Article  CAS  PubMed  Google Scholar 

  4. Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW (2008) Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 111(10):4902–4907. doi:10.1182/blood-2007-10-116327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Connolly GC, Khorana AA, Kuderer NM, Culakova E, Francis CW, Lyman GH (2010) Leukocytosis, thrombosis and early mortality in cancer patients initiating chemotherapy. Thromb Res 126(2):113–118. doi:10.1016/j.thromres.2010.05.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Semrad TJ, O'Donnell R, Wun T, Chew H, Harvey D, Zhou H, White RH (2007) Epidemiology of venous thromboembolism in 9489 patients with malignant glioma. J Neurosurg 106(4):601–608. doi:10.3171/jns.2007.106.4.601

    Article  PubMed  Google Scholar 

  7. Chaichana KL, Pendleton C, Jackson C, Martinez-Gutierrez JC, Diaz-Stransky A, Aguayo J, Olivi A, Weingart J, Gallia G, Lim M, Brem H, Quinones-Hinojosa A (2013) Deep venous thrombosis and pulmonary embolisms in adult patients undergoing craniotomy for brain tumors. Neurol Res 35(2):206–211. doi:10.1179/1743132812Y.0000000126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Seidel C, Hentschel B, Simon M, Schnell O, Heese O, Tatagiba M, Krex D, Reithmeier T, Kowoll A, Weller M, Wick W (2013) A comprehensive analysis of vascular complications in 3,889 glioma patients from the German glioma network. J Neurol 260(3):847–855. doi:10.1007/s00415-012-6718-9

    Article  CAS  PubMed  Google Scholar 

  9. Jenkins EO, Schiff D, Mackman N, Key NS (2010) Venous thromboembolism in malignant gliomas. J Thromb Haemost 8(2):221–227. doi:10.1111/j.1538-7836.2009.03690.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lyman GH, Khorana AA, Falanga A, Clarke-Pearson D, Flowers C, Jahanzeb M, Kakkar A, Kuderer NM, Levine MN, Liebman H, Mendelson D, Raskob G, Somerfield MR, Thodiyil P, Trent D, Francis CW, American Society of Clinical O (2007) American society of clinical oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol : Off J Am Soc Clin Oncol 25(34):5490–5505. doi:10.1200/JCO.2007.14.1283

    Article  CAS  Google Scholar 

  11. Gallus AS (1997) Prevention of post-operative deep leg vein thrombosis in patients with cancer. Thromb Haemost 78(1):126–132

    CAS  PubMed  Google Scholar 

  12. Sartori MT, Della Puppa A, Ballin A, Campello E, Radu CM, Saggiorato G, d’Avella D, Scienza R, Cella G, Simioni P (2013) Circulating microparticles of glial origin and tissue factor bearing in high-grade glioma: a potential prothrombotic role. Thromb Haemost 110(2):378–385. doi:10.1160/TH12-12-0957

    Article  CAS  PubMed  Google Scholar 

  13. Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C, Chin L, DePinho RA, Cavenee WK (2007) Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev 21(21):2683–2710. doi:10.1101/gad.1596707

    Article  CAS  PubMed  Google Scholar 

  14. Sathornsumetee S, Reardon DA, Desjardins A, Quinn JA, Vredenburgh JJ, Rich JN (2007) Molecularly targeted therapy for malignant glioma. Cancer 110(1):13–24. doi:10.1002/cncr.22741

    Article  PubMed  Google Scholar 

  15. Fine HA (2014) Bevacizumab in glioblastoma–still much to learn. N Engl J Med 370(8):764–765. doi:10.1056/NEJMe1313309

    Article  CAS  PubMed  Google Scholar 

  16. Koukourakis GV (2012) Has bevacizumab (avastin) given extra therapeutic gain in metastatic colorectal cancer and malignant brain gliomas? Systematic review answering this question. Recent Patents Inflamm Allergy Drug Discov 6(1):70–77

    Article  CAS  Google Scholar 

  17. Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA (2009) Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol : Off J Am Soc Clin Oncol 27(5):740–745. doi:10.1200/JCO.2008.16.3055

    Article  CAS  Google Scholar 

  18. Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol : Off J Am Soc Clin Oncol 27(28):4733–4740. doi:10.1200/JCO.2008.19.8721

    Article  CAS  Google Scholar 

  19. Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, Jeraj R, Brown PD, Jaeckle KA, Schiff D, Stieber VW, Brachman DG, Werner-Wasik M, Tremont-Lukats IW, Sulman EP, Aldape KD, Curran Jr WJ, Mehta MP (2014) A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370(8):699–708. doi:10.1056/NEJMoa1308573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, Brandes AA, Hilton M, Abrey L, Cloughesy T (2014) Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med 370(8):709–722. doi:10.1056/NEJMoa1308345

    Article  CAS  PubMed  Google Scholar 

  21. Simonetti G, Trevisan E, Silvani A, Gaviani P, Botturi A, Lamperti E, Beecher D, Bertero L, Bosa C, Salmaggi A (2014) Safety of bevacizumab in patients with malignant gliomas: a systematic review. Neurol Sci 35(1):83–89. doi:10.1007/s10072-013-1583-6

    Article  CAS  PubMed  Google Scholar 

  22. Hapani S, Sher A, Chu D, Wu S (2010) Increased risk of serious hemorrhage with bevacizumab in cancer patients: a meta-analysis. Oncology 79(1–2):27–38. doi:10.1159/000314980

    Article  CAS  PubMed  Google Scholar 

  23. Narita Y (2013) Drug review: safety and efficacy of bevacizumab for glioblastoma and other brain tumors. Jpn J Clin Oncol 43(6):587–595. doi:10.1093/jjco/hyt051

    Article  PubMed  Google Scholar 

  24. Wen PY, Schiff D, Kesari S, Drappatz J, Gigas DC, Doherty L (2006) Medical management of patients with brain tumors. J Neuro-Oncol 80(3):313–332. doi:10.1007/s11060-006-9193-2

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shahzaib Nabi.

Ethics declarations

Conflicts of Interest

The authors declare that they have no conflict of interest.

TM has been an advisor to Roche Genentech.

Ethical Approval

The study was approved by the institutional review board (IRB# 9082).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nabi, S., Kahlon, P., Bozorgnia, F. et al. Predictors of Venous Thromboembolism in Patients with Glioblastoma. Pathol. Oncol. Res. 22, 311–316 (2016). https://doi.org/10.1007/s12253-015-0008-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-015-0008-7

Keywords

Navigation