Epidemiology of venous thromboembolism in 9489 patients with malignant glioma

Thomas J. Semrad M.D., Robert O'Donnell M.D., Ph.D., Ted Wun M.D., F.A.C.P., Helen Chew M.D., Danielle Harvey Ph.D., Hong Zhou Ph.D. and Richard H. White M.D., F.A.C.P.
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Object

The authors sought to define the incidence of symptomatic venous thromboembolism (VTE) in patients harboring malignant gliomas.

Methods

The authors conducted a retrospective analysis of data obtained in all cases of malignant glioma diagnosed in California during a 6-year period; the occurrence of a VTE was identified using linked hospital discharge data. The Cox proportional hazard model was used to analyze the association of specific risk factors with the development of a VTE or death within 2 years of the cancer diagnosis.

Among 9489 cases, the 2-year cumulative incidence of VTE was 7.5% (715 cases), with a rate of 16.1 events per 100 person-years during the first 6 months. Three hundred ninety-one (55%) of these 715 cases were diagnosed within 61 days of major neurosurgery. Risk factors for VTE included older age (hazard ratio [HR] 2.6, confidence interval [CI] 2.0–3.4 for age range 65–74 years compared with ≤ 45 years), glioblastoma multiforme histology (HR 1.7, CI 1.4–2.1), three or more chronic comorbidities (HR 3.5, CI 2.8–4.3 [compared with no comorbidity]), and neurosurgery within 61 days (HR 1.7, CI 1.3–2.3). Patients in whom a VTE was present were at higher risk of dying within 2 years (HR 1.3, CI 1.2–1.4). In a nested case–control analysis of all VTE cases, there was no association between insertion of a vena cava filter and the risk of a recurrent VTE.

Conclusions

In patients harboring a glioma there was a very high incidence of symptomatic VTEs, particularly within 2 months of neurosurgery. The development of a VTE was associated with a 30% increase in the risk of death within 2 years. Further studies are needed to determine if risk stratification and the use of medical prophylaxis after neurosurgery improves outcomes.

Abbreviations used in this paper:AA = anaplastic astrocytoma; CI = confidence interval; GBM = glioblastoma multiforme; HR = hazard ratio; ICD-9-CM = International Classification of Diseases, 9th Revision, Clinical Modification; IVC = inferior vena cava; PE = pulmonary embolism; VTE = venous thromboembolism.

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Contributor Notes

Address reprint requests to: Richard H. White, M.D., Division of General Internal Medicine, University of California at Davis, Suite 2400, 4150 V Street, Sacramento, California 95817. email: rhwhite@ucdavis.edu.
  • 1

    Agnelli G, , Piovella F, , Buoncristiani P, , Severi P, , Pini M, & D'Angelo A, : Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery. N Engl J Med 339:8085, 1998

    • Search Google Scholar
    • Export Citation
  • 2

    Aguilar D, & Goldhaber SZ: Clinical uses of low-molecular-weight heparins. Chest 115:14181423, 1999

  • 3

    Alcalay A, , Wun T, , Khatri V, , Chew HK, , Harvey D, & Zhou H, : Venous thromboembolism in patients with colorectal cancer: incidence and effect on survival. J Clin Oncol 24:11121118, 2006

    • Search Google Scholar
    • Export Citation
  • 4

    Bastida E, , Ordinas A, , Escolar G, & Jamieson GA: Tissue factor in microvesicles shed from U87MG human glioblastoma cells induces coagulation, platelet aggregation, and thrombogenesis. Blood 64:177184, 1984

    • Search Google Scholar
    • Export Citation
  • 5

    Brandes AA, , Scelzi E, , Salmistraro G, , Ermani M, , Carollo C, & Berti F, : Incidence of risk of thromboembolism during treatment high-grade gliomas: a prospective study. Eur J Cancer 33:15921596, 1997

    • Search Google Scholar
    • Export Citation
  • 6

    Bucci MN, , Papadopoulos SM, , Chen JC, , Campbell JA, & Hoff JT: Mechanical prophylaxis of venous thrombosis in patients undergoing craniotomy: a randomized trial. Surg Neurol 32:285288, 1989

    • Search Google Scholar
    • Export Citation
  • 7

    Buckner JC: Factors influencing survival in high-grade gliomas. Semin Oncol 30:19 Suppl 1014, 2003

  • 8

    Chan AT, , Atiemo A, , Diran LK, , Licholai GP, , McLaren Black P, & Creager MA, : Venous thromboembolism occurs frequently in patients undergoing brain tumor surgery despite prophylaxis. J Thromb Thrombolysis 8:139142, 1999

    • Search Google Scholar
    • Export Citation
  • 9

    Chang SM, , Parney IF, , Huang W, , Anderson FA Jr, , Asher AL, & Bernstein M, : Patterns of care for adults with newly diagnosed malignant glioma. JAMA 293:557564, 2005

    • Search Google Scholar
    • Export Citation
  • 10

    Cheruku R, , Tapazoglou E, , Ensley J, , Kish JA, , Cummings GD, & al-Sarraf M: The incidence and significance of thromboembolic complications in patients with high-grade gliomas. Cancer 68:26212624, 1991

    • Search Google Scholar
    • Export Citation
  • 11

    Chew HK, , Wun T, , Harvey D, , Zhou H, & White RH: Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 166:458464, 2006

    • Search Google Scholar
    • Export Citation
  • 12

    Choucair AK, , Silver P, & Levin VA: Risk of intracranial hemorrhage in glioma patients receiving anticoagulant therapy for venous thromboembolism. J Neurosurg 66:357358, 1987

    • Search Google Scholar
    • Export Citation
  • 13

    Clagett GP, , Anderson FA Jr, , Heit J, , Levine MN, & Wheeler HB: Prevention of venous thromboembolism. Chest 108:4 Suppl 312S334S, 1995

  • 14

    Dhami MS, , Bona RD, , Calogero JA, & Hellman RM: Venous thromboembolism and high grade gliomas. Thromb Haemost 70:393396, 1993

  • 15

    Elixhauser A, , Steiner C, , Harris DR, & Coffey RM: Comorbidity measures for use with administrative data. Med Care 36:827, 1998

  • 16

    Fisher LD, & Lin DY: Time-dependent covariates in the Cox proportional-hazards regression model. Annu Rev Public Health 20:145157, 1999

    • Search Google Scholar
    • Export Citation
  • 17

    Haas S: Venous thromboembolism in medical patients—the scope of the problem. Semin Thromb Hemost 29:1 Suppl 1721, 2003

  • 18

    Hamilton MG, , Hull RD, & Pineo GF: Venous thromboembolism in neurosurgery and neurology patients: a review. Neurosurgery 34:280296, 1994

    • Search Google Scholar
    • Export Citation
  • 19

    Iberti TJ, , Miller M, , Abalos A, , Fischer EP, , Post KD, & Benjamin E, : Abnormal coagulation profile in brain tumor patients during surgery. Neurosurgery 34:389395, 1994

    • Search Google Scholar
    • Export Citation
  • 20

    Kayser-Gatchalian MC, & Kayser K: Thrombosis and intracranial tumors. J Neurol 209:217224, 1975

  • 21

    Levitan N, , Dowlati A, , Remick SC, , Tahsildar HI, , Sivinski LD, & Beyth R, : Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data. Medicine (Baltimore) 78:285291, 1999

    • Search Google Scholar
    • Export Citation
  • 22

    Lip GY, , Chin BS, & Blann AD: Cancer and the prothrombotic state. Lancet Oncol 3:2734, 2002

  • 23

    Marras LC, , Geerts WH, & Perry JR: The risk of venous thromboembolism is increased throughout the course of malignant glioma: an evidence-based review. Cancer 89:640646, 2000

    • Search Google Scholar
    • Export Citation
  • 24

    Quevedo JF, , Buckner JC, , Schmidt JL, , Dinapoli RP, & O'Fallon JR: Thromboembolism in patients with high-grade glioma. Mayo Clin Proc 69:329332, 1994

    • Search Google Scholar
    • Export Citation
  • 25

    Rodas RA, , Fenstermaker RA, , McKeever PE, , Blaivas M, , Dickinson LD, & Papadopoulos SM, : Correlation of intraluminal thrombosis in brain tumor vessels with postoperative thrombotic complications: a preliminary report. J Neurosurg 89:200205, 1998

    • Search Google Scholar
    • Export Citation
  • 26

    Ruff RL, & Posner JB: Incidence and treatment of peripheral venous thrombosis in patients with glioma. Ann Neurol 13:334336, 1983

  • 27

    Sawaya R, & Glas-Greenwalt P: Postoperative venous thromboembolism and brain tumors: Part II. Hemostatic profile. J Neurooncol 14:127134, 1992

    • Search Google Scholar
    • Export Citation
  • 28

    Stein PD, , Beemath A, , Meyers FA, , Skaf E, , Sanchez J, & Olson RE: Incidence of venous thromboembolism in patients hospitalized with cancer. Am J Med 119:6068, 2006

    • Search Google Scholar
    • Export Citation
  • 29

    Streiff MB, , Segal J, , Grossman SA, , Kickler TS, & Weir EG: ABO blood group is a potent risk factor for venous thromboembolism in patients with malignant gliomas. Cancer 100:17171723, 2004

    • Search Google Scholar
    • Export Citation
  • 30

    Stukenborg GJ, , Wagner DP, & Connors AF Jr: Comparison of the performance of two comorbidity measures, with and without information from prior hospitalizations. Med Care 39:727739, 2001

    • Search Google Scholar
    • Export Citation
  • 31

    Stupp R, , Mason WP, , van den Bent MJ, , Weller M, , Fisher B, & Taphoorn MJ, : Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987996, 2005

    • Search Google Scholar
    • Export Citation
  • 32

    Takano S, , Tsuboi K, , Tomono Y, , Mitsui Y, & Nose T: Tissue factor, osteopontin, alphavbeta3 integrin expression in microvasculature of gliomas associated with vascular endothelial growth factor expression. Br J Cancer 82:19671973, 2000

    • Search Google Scholar
    • Export Citation
  • 33

    Turpie AG, , Hirsh J, , Gent M, , Julian D, & Johnson J: Prevention of deep vein thrombosis in potential neurosurgical patients. A randomized trial comparing graduated compression stockings alone or graduated compression stockings plus intermittent pneumatic compression with control. Arch Intern Med 149:679681, 1989

    • Search Google Scholar
    • Export Citation
  • 34

    White RH, , Beyth RJ, , Zhou H, & Romano PS: Major bleeding after hospitalization for deep-venous thrombosis. Am J Med 107:414424, 1999

  • 35

    White RH, , Gettner S, , Newman JM, , Trauner KB, & Romano PS: Predictors of rehospitalization for symptomatic venous thromboembolism after total hip arthroplasty. N Engl J Med 343:17581764, 2000

    • Search Google Scholar
    • Export Citation
  • 36

    White RH, , Zhou H, & Gage BF: Effect of age on the incidence of venous thromboembolism after major surgery. J Thromb Haemost 2:13271333, 2004

    • Search Google Scholar
    • Export Citation
  • 37

    White RH, , Zhou H, , Kim J, & Romano PS: A population-based study of the effectiveness of inferior vena cava filter use among patients with venous thromboembolism. Arch Intern Med 160:20332041, 2000

    • Search Google Scholar
    • Export Citation
  • 38

    White RH, , Zhou H, , Murin S, & Harvey D: Effect of ethnicity and gender on the incidence of venous thromboembolism in a diverse population in California in 1996. Thromb Haemost 93:298305, 2005

    • Search Google Scholar
    • Export Citation
  • 39

    White RH, , Zhou H, & Romano PS: Incidence of idiopathic deep venous thrombosis and secondary thromboembolism among ethnic groups in California. Ann Intern Med 128:737740, 1998

    • Search Google Scholar
    • Export Citation
  • 40

    Wun T, , Law L, , Harvey D, , Sieracki B, , Scudder SA, & Ryu JK: Increased incidence of symptomatic venous thrombosis in patients with cervical carcinoma treated with concurrent chemotherapy, radiation, and erythropoietin. Cancer 98:15141520, 2003

    • Search Google Scholar
    • Export Citation

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