Epidemiology of venous thromboembolism in 9489 patients with malignant glioma

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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.

Article Information

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.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Kaplan–Meier plot of the incidence of VTE after the diagnosis of malignant glioma.

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    Kaplan–Meier plot of the incidence of recurrent VTE in patients with glioma in whom an IVC filter was and was not placed.

References

1

Agnelli GPiovella FBuoncristiani PSeveri PPini MD'Angelo A: Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery. N Engl J Med 339:80851998

2

Aguilar DGoldhaber SZ: Clinical uses of low-molecular-weight heparins. Chest 115:141814231999

3

Alcalay AWun TKhatri VChew HKHarvey DZhou H: Venous thromboembolism in patients with colorectal cancer: incidence and effect on survival. J Clin Oncol 24:111211182006

4

Bastida EOrdinas AEscolar GJamieson GA: Tissue factor in microvesicles shed from U87MG human glioblastoma cells induces coagulation, platelet aggregation, and thrombogenesis. Blood 64:1771841984

5

Brandes AAScelzi ESalmistraro GErmani MCarollo CBerti F: Incidence of risk of thromboembolism during treatment high-grade gliomas: a prospective study. Eur J Cancer 33:159215961997

6

Bucci MNPapadopoulos SMChen JCCampbell JAHoff JT: Mechanical prophylaxis of venous thrombosis in patients undergoing craniotomy: a randomized trial. Surg Neurol 32:2852881989

7

Buckner JC: Factors influencing survival in high-grade gliomas. Semin Oncol 30:19 Suppl10142003

8

Chan ATAtiemo ADiran LKLicholai GPMcLaren Black PCreager MA: Venous thromboembolism occurs frequently in patients undergoing brain tumor surgery despite prophylaxis. J Thromb Thrombolysis 8:1391421999

9

Chang SMParney IFHuang WAnderson FA JrAsher ALBernstein M: Patterns of care for adults with newly diagnosed malignant glioma. JAMA 293:5575642005

10

Cheruku RTapazoglou EEnsley JKish JACummings GDal-Sarraf M: The incidence and significance of thromboembolic complications in patients with high-grade gliomas. Cancer 68:262126241991

11

Chew HKWun THarvey DZhou HWhite RH: Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 166:4584642006

12

Choucair AKSilver PLevin VA: Risk of intracranial hemorrhage in glioma patients receiving anticoagulant therapy for venous thromboembolism. J Neurosurg 66:3573581987

13

Clagett GPAnderson FA JrHeit JLevine MNWheeler HB: Prevention of venous thromboembolism. Chest 108:4 Suppl312S334S1995

14

Dhami MSBona RDCalogero JAHellman RM: Venous thromboembolism and high grade gliomas. Thromb Haemost 70:3933961993

15

Elixhauser ASteiner CHarris DRCoffey RM: Comorbidity measures for use with administrative data. Med Care 36:8271998

16

Fisher LDLin DY: Time-dependent covariates in the Cox proportional-hazards regression model. Annu Rev Public Health 20:1451571999

17

Haas S: Venous thromboembolism in medical patients—the scope of the problem. Semin Thromb Hemost 29:1 Suppl17212003

18

Hamilton MGHull RDPineo GF: Venous thromboembolism in neurosurgery and neurology patients: a review. Neurosurgery 34:2802961994

19

Iberti TJMiller MAbalos AFischer EPPost KDBenjamin E: Abnormal coagulation profile in brain tumor patients during surgery. Neurosurgery 34:3893951994

20

Kayser-Gatchalian MCKayser K: Thrombosis and intracranial tumors. J Neurol 209:2172241975

21

Levitan NDowlati ARemick SCTahsildar HISivinski LDBeyth R: Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data. Medicine (Baltimore) 78:2852911999

22

Lip GYChin BSBlann AD: Cancer and the prothrombotic state. Lancet Oncol 3:27342002

23

Marras LCGeerts WHPerry JR: The risk of venous thromboembolism is increased throughout the course of malignant glioma: an evidence-based review. Cancer 89:6406462000

24

Quevedo JFBuckner JCSchmidt JLDinapoli RPO'Fallon JR: Thromboembolism in patients with high-grade glioma. Mayo Clin Proc 69:3293321994

25

Rodas RAFenstermaker RAMcKeever PEBlaivas MDickinson LDPapadopoulos SM: Correlation of intraluminal thrombosis in brain tumor vessels with postoperative thrombotic complications: a preliminary report. J Neurosurg 89:2002051998

26

Ruff RLPosner JB: Incidence and treatment of peripheral venous thrombosis in patients with glioma. Ann Neurol 13:3343361983

27

Sawaya RGlas-Greenwalt P: Postoperative venous thromboembolism and brain tumors: Part II. Hemostatic profile. J Neurooncol 14:1271341992

28

Stein PDBeemath AMeyers FASkaf ESanchez JOlson RE: Incidence of venous thromboembolism in patients hospitalized with cancer. Am J Med 119:60682006

29

Streiff MBSegal JGrossman SAKickler TSWeir EG: ABO blood group is a potent risk factor for venous thromboembolism in patients with malignant gliomas. Cancer 100:171717232004

30

Stukenborg GJWagner DPConnors AF Jr: Comparison of the performance of two comorbidity measures, with and without information from prior hospitalizations. Med Care 39:7277392001

31

Stupp RMason WPvan den Bent MJWeller MFisher BTaphoorn MJ: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:9879962005

32

Takano STsuboi KTomono YMitsui YNose T: Tissue factor, osteopontin, alphavbeta3 integrin expression in microvasculature of gliomas associated with vascular endothelial growth factor expression. Br J Cancer 82:196719732000

33

Turpie AGHirsh JGent MJulian DJohnson 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 149:6796811989

34

White RHBeyth RJZhou HRomano PS: Major bleeding after hospitalization for deep-venous thrombosis. Am J Med 107:4144241999

35

White RHGettner SNewman JMTrauner KBRomano PS: Predictors of rehospitalization for symptomatic venous thromboembolism after total hip arthroplasty. N Engl J Med 343:175817642000

36

White RHZhou HGage BF: Effect of age on the incidence of venous thromboembolism after major surgery. J Thromb Haemost 2:132713332004

37

White RHZhou HKim JRomano PS: A population-based study of the effectiveness of inferior vena cava filter use among patients with venous thromboembolism. Arch Intern Med 160:203320412000

38

White RHZhou HMurin SHarvey D: Effect of ethnicity and gender on the incidence of venous thromboembolism in a diverse population in California in 1996. Thromb Haemost 93:2983052005

39

White RHZhou HRomano PS: Incidence of idiopathic deep venous thrombosis and secondary thromboembolism among ethnic groups in California. Ann Intern Med 128:7377401998

40

Wun TLaw LHarvey DSieracki BScudder SARyu JK: Increased incidence of symptomatic venous thrombosis in patients with cervical carcinoma treated with concurrent chemotherapy, radiation, and erythropoietin. Cancer 98:151415202003

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