Venous Thromboembolism in Brain Tumor Patients: A Review of Literature
Journal of Hematology & Thromboembolic Diseases

Journal of Hematology & Thromboembolic Diseases
Open Access

ISSN: 2329-8790

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Review Article - (2015) Volume 3, Issue 2

Venous Thromboembolism in Brain Tumor Patients: A Review of Literature

David J. Cote and Timothy R. Smith*
Department of Neurosurgery, Brigham and Women’s Hospital, Boston, MA, USA
*Corresponding Author: Timothy R. Smith, Department of Neurosurgery, Brigham and Women’s Hospital, 15 Francis Street–PBB3, Boston, MA-02115, USA, Tel: +617 525 8371, Fax: 617 734 8342 Email:


Venous thromboembolism (VTE) is a relatively common and well-described condition, affecting approximately 1-2% of the general population. VTE can lead to significant morbidity and death via pulmonary embolism (PE). During the post-operative period, VTE occurs at higher rates due to natural thrombotic responses to injury and limited post-operative mobility. In general, rates of post-operative VTE are higher in patients undergoing operations for cranial and spinal lesions than for lesions of other types, a phenomenon that is not fully explained. Several studies have demonstrated that other risk factors for VTE include age, sex, ethnicity, hospital stay length, and coagulation state. Aggressive chemical and mechanical measures for VTE prophylaxis are indicated in the postoperative period to prevent the formation of VTE. Here we review the literature on VTE in brain tumor patients, with a focus on their etiology, diagnosis, treatment, and prophylaxis.

Keywords: Venous thromboembolism; Brain tumor; Deep vein thrombosis; Pulmonary embolism; Thromboprophylaxis


Venous thromboemboli (VTE) occur regularly in 1-2% of the general population, with an annual incidence of 1 in 500 [1,2]. VTE can cause death via pulmonary emboli (PE) or significant disability via pain, edema, and post-thrombotic syndrome, a form of venous reflux that occurs secondary to deep vein thrombosis (DVT). VTE occurs at a higher rate during the post-operative period due to natural thrombotic responses to injury and limited post-operative mobility. Patients harboring brain tumors are more likely to develop VTE than patients who have cancers in other sites (Table 1) [3-24]. Studies have shown that other risk factors for VTE include age, sex, ethnicity, blood type, length of hospital stay, operative duration, and coagulation status [3,6,8-10,14,25-38]. Standard prophylactic measures for VTE include chemical anticoagulation, mechanical prophylaxis, and increased ambulation during the post-operative period [36,39-54].

  Diagnoses/100 Hospitalizations
Cancer Type/Site VTE PE DVT
Pancreas 4.3 1.2 3.5
Brain 3.5 1.0 2.8
Myeloproliferative, other lymphatic/hematopoetic 2.9 * 2.5
Stomach 2.7 0.7 2.3
Lymphoma, lymphosarcoma, reticulosarcoma 2.5 0.6 2.0
Uterus 2.2 0.5 1.8
Trachea, bronchus, and lung 2.1 0.6 1.6
Esophagus 2.0 * 1.3
Prostate 2.0 0.6 1.6
Rectum, rectosigmoid junction, anus 2.1 0.7 1.4
Kidney 2.0 0.5 1.6
Colon 1.9 0.6 1.4
Ovary 2.0 0.5 1.6
Liver, gallbladder, intra- and extrahepatic ducts 1.8 0.9 1.1
Leukemia 1.7 0.4 1.4
Breast (female) 1.7 0.4 1.3
Cervix 1.6 * 1.4
Bladder 1.0 0.3 0.8
Lip, oral cavity, pharynx <0.6 * *
No cancer 1.0 0.3 0.8
^Table adapted from Stein et al. [15], *Insufficient data

Table 1: Rate of VTE in patients with various types of cancer^.

This paper seeks to review the relevant and current literature on VTE in brain tumor patients, with particular focus on the risk factors and presenting symptoms of VTE, treatment options for those with VTE, and a review of current prophylactic measures for VTE.


Several factors are thought to drive the formation of VTE. Most prominently, these include venous stasis, blood hypercoagulability, and damage to blood vessel walls [2,55]. Unlike typical blood clots, which form as a collection of erythrocytes on a fibrin mesh, VTE develop in several laminar layers of platelets, leukocytes, and fibrin, which surround a nucleus of erythrocytes [2,56]. Venous blood velocity is much slower than arterial blood flow [57]. Combined with the surface of venous valves and the dilated sinuses of the lower extremities, this relative stasis has been proposed as a potential source of VTE [57]. Venous stasis and blood hypercoagulability promote adherence to collection sites, while damage to vessels exposes the collagen-rich interior of vascular walls. Collagen-rich walls have been reported to promote platelet aggregation, which further incites formation of VTE through collection of leukocytes [55,56].

Inflammation is another proposed contributor to the formation of VTE, in large part because of its role in promoting platelet reactivity and increasing circulating complexes like tissue factor (TF) and fibrinogen. Bucek et al. demonstrated that the inflammatory marker C-reactive protein (CRP) increases in patients with DVT and therefore can be considered a potential indicator of the presence of VTE [58]. The endothelium, which expresses pro- and anti-coagulants, as well as vasoconstrictors and vasodilators, plays a prominent role in the development of VTE via inflammation. Wakefield et al. report that when the endothelium is disturbed, either functionally or mechanically, the endothelial surface vasoconstricts and reacts in a prothrombotic fashion. Endothelial cells release pro-thrombotic factors including platelet activating factor (PAF), endothelin-1 (a vasoconstrictor), von Willebrand factor, TF, and plasminogen activator inhibitor [55]. Injury to the endothelium also promotes surface expression of cell adhesion molecules like P-selectin and E-selectin, which promote leukocyte margination and adhesion [55]. The net effect of these inflammatory cascades following injury or disruption of venous vessels promotes VTE development.

VTE in Brain Tumor Patients

Although VTE is relatively common in the general population, it is far more common during the post-operative period [25,27,39-42,51-53]. Proposed explanations for this phenomenon include limited post-operative mobility, which can promote venous stasis, and damage to endothelial tissue, as discussed above.

Several studies have shown that patients harboring brain tumors develop DVT at a higher rate than patients with cancer at other sites or patients undergoing procedures for diseases other than cancer (Table 1) [18,20,59]. Day et al. recently reported a VTE rate of 1.2% for lower extremity arthroplasties, and only 0.53% for shoulder arthroplasties [60]. In a study of patients undergoing operations for lung cancer, on the other hand, Christensen et al. reported a mean risk of 2.0% [61]. Stein et al. report the rate of VTE in brain cancer patients, on the other hand, to be 3.5 diagnoses per 100 hospitalizations [15]. In a separate study of more than 1,000 brain tumor patients, the rate of VTE was 19.4%, though this may be artificially elevated in part due to more aggressive surveillance for DVT and PE.17 In an investigation of site-specific cancer and its relation to VTE formation, Petterson et al. found that brain cancer resulted in one of the highest rates of VTE formation, even after adjusting for complicating factors like age and sex [23].

Many mechanisms have been proposed for the increased rate of VTE in patients with cancer. Several studies have investigated circulating microparticles (MP) in the blood, which originate from cancer cells and often express TF. In 2011, Sartori et al. studied the procoagulant activity of circulating MPs in patients harboring glioblastoma multiforme (GBM). They found that MP activity levels increased in 63.6% of 61 patients who underwent resection of GBM, a statistically significant association (chi2=4.93, p=0.026) [62]. In 2004, Browd et al. demonstrated that DVT formation in patients undergoing neurosurgery has been reported as high as 25%, with mortality rates from PE ranging from 9 to 50% [63]. A study by Khorana et al. of patients with pancreatic cancer further indicated that increased plasma TF—a physiologic initiator of coagulation-is correlated with development of VTE in the post-operative period [64]. The authors also suggest that cancer cells are a potential source of circulating TF, which could be an explanation for the increased rate of VTE in cancer patients [65]. Not all cancers produce these procoagulant effects equally, however, which leads to the disparity in VTE rate between tumors of the brain and cancers of other sites. For example, studies have shown that high-grade tumors of the brain result in a higher concentration of TF, with an associated higher rate of VTE development [62]. A study of 1000 patients undergoing operations for brain tumors showed a strong correlation between higher tumor grade and DVT development (Table 2) [14,17].

Tumor Type DVT+/Total Patients (%)
Metastasis 44/185 (23.8)
High Grade Glioma 53/248 (21.4)
Low Grade Glioma 5/28 (17.6)
Meningioma 16/196 (8.2)
High Grade Oligodendroglioma 3/15 (20.0)
Low Grade Oligodendroglioma 2/16 (12.5)
Mixed 3/9 (33.3)
Sarcoma 0/3 (0.0)
Schwanomma 4/22 (18.2)
Acoustic Neuroma 0/1 (0.0)
Medulloblastoma 0/6 (0.0)
Lymphoma 8/27 (29.6)
Pituitary Adenoma 0/10 (0.0)
Ependymoma 0/6 (0.0)
Hemangiopericytoma 1/4(25.0)
Choroid 0/3 (0.0)
Hemangioblastoma 2/9 (22.2)
Other 15/88 (17.0)
*Table adapted from Smith et al. [17].

Table 2: DVT development by brain tumor type*.

Risk Factors

Risk factors for VTE are well-described in the literature, and many studies have examined a range of variables for their effect on rate of VTE development (Table 3) [66]. The most commonly reported risk factor for VTE is age. In 1994, Kniffin et al. report that the annual incidence rates per 1000 from age 65 to 69 is 1.3 for PE and 1.8 for DVT. The incidence rates increased steadily with age: at 85 to 89, the annual incidence rates were 2.8 and 3.1, respectively [29]. In 2004, a study by Stein et al. corroborated these results, demonstrating that patients aged 30 to 39 years have a two-fold higher risk of DVT or PE compared to younger patients, while patients 70 years or older have an 18- to 28-fold increase in risk of DVT or PE than those aged 20 to 29 years [67].

Risk Factor Univariate OR (95% cl)^ Multivariate OR (95% cl)^
Age   1.03 (1.02-1.03)
Weight   1.01 (1.01-1.01)
CNS Tumor 3.69 (3.00-4.52) 2.24 (1.71-2.94)
Sex 0.84 (0.72-0.98)  
Hemiparesis prior to surgery 4.25 (3.27-5.52) 1.80 (1.32-2.45)
Paraparesis 2.56 (1.78-3.69)  
Quadraparesis 3.78 (2.00-7.17)  
Tobacco Use 0.60 (0.48-0.73)  
*Table adapted from Rolston et al. [62], ^All OR are statistically significant

Table 3: Risk factors for development of post-operative VTE in neurosurgical patients*.

A separate study by Geerts et al. suggested that age higher than 40 years is an important risk factor for development of VTE [68]. Other risk factors for the development of VTE that have been explored in the literature include sex, ethnicity post-operative ICU days, anti-coagulation state, and blood type [15,17,65].

In the case of patients harboring brain tumors, several risk factors for VTE development are of particular concern. Many patients undergoing operations for tumors of the central nervous system suffer hemi-, para-, or quadraparesis, either as a result of their tumor pre-operatively, or as a post-operative complication, which can promote DVT development by limiting ambulation [66]. Studies have also demonstrated that patients on steroids have a higher rate of VTE—often, steroids are prescribed as a post-operative regimen after transcranial operations. Patients who have undergone chemotherapy or radiation—both common treatments for many brain lesions—also develop VTE at a much higher rate than those who have not [66]. A particularly unique risk factor for patients harboring brain tumors is the tumor itself, which, as discussed above, can act in a prothrombotic fashion that differs by tumor histology [17]. Studies have shown that tumors of a high grade (e.g., high-grade gliomas and oligodendrogliomas) are more likely to result in post-operative VTE than tumors of a lower grade (e.g., meningioma, pituitary adenoma) [14,17].

Presenting Signs and Symptoms

Patients with VTE present with a variety of signs and symptoms. These vary based on the location of VTE (e.g., PE vs. DVT) but help the practitioner establish the diagnosis and localize the thrombosis. In the case of DVT, patients often present with pain and edema of the affected extremity [69-71]. Other symptoms include tenderness of the extremity, sometimes with a palpable mass, skin blanching, and excessive warmth or redness in the extremity [16,31,43,69]. In the case of PE, common presenting signs and symptoms include dyspnea, pleuritic pain, cough, hemoptysis, and palpitation [69,72]. VTE (especially DVT) is occasionally found in patients that are asymptomatic.

When a patient presents with clinical signs and symptoms of VTE, final diagnosis is often made radiographically. For DVT, upper/lower extremity ultrasound is often sufficient to locate and image the embolus [42,72]. In the case of PE, more common radiographic techniques include chest CT scans and V/Q scans [14,26,31,71].



Chemical prophylaxis for VTE is extremely common, and most often involves the administration of low-dose or low molecular weight heparin, or enoxaparin. In a meta-analysis of general surgical patients, Clagett et al. demonstrated that the administration of low-dose heparin was effective in preventing the formation of DVT [32,73]. Other studies, however, have demonstrated that sometimes heparin is ineffective in preventing VTE [74].

In neurosurgical patients, one of the primary concerns after the administration of heparin or other anti-coagulants is the risk of intracranial hemorrhage. Patients undergoing transcranial operations for tumors or vascular lesions are already at an increased risk for hemorrhage, and the addition of anti-coagulant medication has been proposed as a potential risk factor for higher rates of hemorrhage among neurosurgical patients. Data on this association have been mixed. Some studies have demonstrated an increased rate of intracranial hemorrhage when VTE chemoprophylaxis is initiated pre-operatively [45]. Other studies have demonstrated no statistically significant association between the two [75-78].


Intermittent pneumatic compression (IPC) and compression stockings are the most common forms of mechanical prophylaxis for VTE [79]. In a systematic meta-analysis, Vanek et al. demonstrated that IPC decreased the risk of DVT by 62% compared to a placebo, 47% compared to high-pressure stockings, and 48% compared to low molecular weight heparin [80]. In a randomized trial of neurosurgery patients, Turpie et al. corroborated this data by reporting the incidence of DVT at 8.8% in patients using high-pressure stockings, 9% in patients using IPC, and 19.8% in an untreated control group [81]. Kurtoglu et al. similarly reported that IPC was as effective as low molecular weight heparin in DVT prophylaxis following head and spinal trauma [32]. Often, IPC and compression stockings are combined for use in a single patient. Although effective at preventing DVT, Vanek et al. report that IPC and compression stockings have no effect on the rate of PE formation [80].

Because paresis and limited post-operative mobility are often reported as risk factors for the development of DVT, post-operative ambulation is encouraged for prophylactic purposes. Intervention with physical therapy for patients who are not ambulatory is often employed as an additional prophylactic. Post-operative ambulation and exercise can help prevent venous stasis, which contributes to the development of VTE as described above [30,34,39,40,68].

Combined prophylaxis

Because both mechanical and chemical prophylaxis are effective at reducing the rate of VTE development during the post-operative period, they are frequently prescribed simultaneously as combined prophylaxis. Several studies have compared the effectiveness of chemical anticoagulation with the effectiveness of mechanical prophylaxis [7,32,36,45,52,74,82]. Many of these studies show that combined prophylaxis has a higher effectiveness in preventing VTE without increasing risk to the patient than either method alone (Table 4) [82].

Reference Combination (%) Compression (%) Risk Ratio
Agnelli et al. [75] 22/153 (14) 42/154 (27) 0.53 (0.33-0.84)
Dickinson et al. [43] 4/23 (17) 3/22 (14) 1.28 (0.32-5.06)
Nurmohamed et al. [42] 32/241 (13) 49/244 (20) 0.66 (0.44-0.99)
Subtotal 58/417 (14) 94/420 (22) 0.62 (0.46-0.84)
*Table adapted from Zareba et al. [78].

Table 4: Effectiveness of compression vs. anticoagulation and compression combined in preventing post-operative VTE after neurosurgery*.

Timing of prophylaxis

Proper timing of prophylaxis for development of VTE in surgical patients remains controversial. Many guidelines have been put forth regarding proper type, timing, and administration of VTE prophylaxis. The American Society of Clinical Oncology (ASCO), in its 2007 guidelines on VTE prophylaxis in patients with cancer, recommends that all patients with cancer undergoing major surgery for malignant disease should be considered for pharmacologic thromboprophylaxis, and endorses low molecular weight heparin as the “preferred agent” for treatment of VTE [83]. Nevertheless, the society’s recommendations remain purposefully open, leaving most of the decision on VTE prophylaxis up to the treatment team based on the clinical details of each particular patient. In a 2015 update to the 2007 guidelines, the ASCO provided similar recommendations, expanding their guidelines to include stronger language regarding the necessity of VTE prophylaxis in most hospitalized cancer patients. The American College of Chest Physicians and the Canadian Association of Gastroenterology also lobby for chemoprophylaxis of patients at risk for VTE, but do not provide specific recommendations on the timing, type, or duration of that prophylaxis.

In the case of patients with brain tumors, neurosurgeons are often wary of prescribing pre-operative anticoagulants that may be employed in other types of surgery due to the risk of intracranial hemorrhage intra- or immediately post-op [84]. Intracranial hemorrhage poses a serious risk to the patient’s cognitive and functional outcome, and can lead to re-operations and iatrogenic morbidity. In other disciplines, the administration of pre-operative chemical anti-coagulants remains more generally accepted because of lower danger of complications from intra-operative bleeding. For patients with brain tumors, pre-operative anticoagulation is generally discouraged [5,7,17,30,47,49,52,53].

For the same reason, neurosurgeons are often overly cautious of prescribing chemical anticoagulants during the post-operative period, particularly in the case of brain tumor patients. Several studies have shown that the rates of post-operative hemorrhage are higher in patients undergoing resection of a brain tumor than those in patients undergoing trauma or spinal neurosurgery [32,52,76,77]. Carman et al. surveyed American neurosurgeons and reported that, generally, they underestimate the risk of DVT after brain surgery, and tend to avoid the use of chemoprophylaxis [84]. They remain committed to VTE prophylaxis via mechanical means, however, almost universally providing patients with some form of mechanical prophylaxis (e.g., ICP). This mechanical prophylaxis is often used without combined chemical prophylaxis, however [84]. Despite mounting evidence of both their safety and efficacy, chemical anticoagulants are underprescribed by neurosurgeons during the post-operative period [32,75,77,78,82,84].

Treatment for VTE

There are several methods for treating VTE. The first line of treatment is chemical anticoagulation, usually with heparin [43,55,70,81]. Treatment with heparin often resolves VTE and its associated symptoms. In some cases, however, anticoagulation is contraindicated. Contraindicated patients include patients who are non-ambulatory or comatose. Treatment with anticoagulants in these cases can lead to hemorrhage and associated morbidity and mortality.

When anticoagulants are contraindicated, VTE can be treated endovascularly, most often with filters. VTE filters are placed most frequently in the inferior vena cava (IVC) to prevent a circulating clot from becoming a PE. IVC filters have been shown to be extremely effective in preventing the development of PE and in decreasing the morbidity and mortality of patients known to be harboring VTE of any kind [10,11,32,34].


Although VTE can be common, prevention is possible in brain tumor patients. Post-operative VTE chemoprophylaxis, when prescribed appropriately, is a safe treatment option for patients who are at high risk for VTE (e.g., patients undergoing transcranial operations). Despite this, many neurosurgeons remain wary of prescribing prophylactic doses of anticoagulants during the post-operative period. The rate of VTE development in the post-operative period for brain tumor patients can be significantly decreased by effective use of both chemical and mechanical thromboprophylaxis.


  1. F owkes FJ, Price JF, Fowkes FG (2003) Incidence of diagnosed deep vein thrombosis in the general population: systematic review. European journal of vascular and endovascular surgery: the official journal of the European Society for Vascular Surgery 25: 1-5.
  2. Saha P, Humphries J, Modarai B, Mattock K, Waltham M, et al. (2011) Leukocytes and the natural history of deep vein thrombosis: current concepts and future directions. ArteriosclerThrombVascBiol 31: 506-512.
  3. Brandes AA, Scelzi E, Salmistraro G, Ermani M, Carollo C, et al. (1997) Incidence of risk of thromboembolism during treatment high-grade gliomas: a prospective study. Eur J Cancer 33: 1592-1596.
  4. Rodas RA, Fenstermaker RA, McKeever PE, Blaivas M, Dickinson LD, et al. (1998) Correlation of intraluminal thrombosis in brain tumor vessels with postoperative thrombotic complications: a preliminary report. J Neurosurg 89: 200-205.
  5. Marras LC, Geerts WH, Perry JR (2000) The risk of venous thromboembolism is increased throughout the course of malignant glioma: an evidence-based review. Cancer 89: 640-646.
  6. Walsh DC, Kakkar AK (2001) Thromboembolism in brain tumors. CurrOpinPulm Med 7: 326-331.
  7. Smith SF, Simpson JM, Sekhon LH (2004) Prophylaxis for deep venous thrombosis in neurosurgical oncology: review of 2779 admissions over a 9-year period. Neurosurg Focus 17: E4.
  8. Streiff MB, Segal J, Grossman SA, Kickler TS, Weir EG (2004) ABO blood group is a potent risk factor for venous thromboembolism in patients with malignant gliomas. Cancer 100: 1717-1723.
  9. Chiocca EA, Schwartzbaum JA (2007) Gliomas and venous thromboembolism: how common? J Neurosurg 106: 599-600.
  10. Semrad TJ, O'Donnell R, Wun T, Chew H, Harvey D, et al. (2007) Epidemiology of venous thromboembolism in 9489 patients with malignant glioma. J Neurosurg 106: 601-608.
  11. Ghanim AJ, Daskalakis C, Eschelman DJ, Kraft WK (2007) A five-year, retrospective, comparison review of survival in neurosurgical patients diagnosed with venous thromboembolism and treated with either inferior vena cava filters or anticoagulants. J Thromb Thrombolysis 24: 247-254.
  12. Jenkins EO, Schiff D, Mackman N, Key NS (2010) Venous thromboembolism in malignant gliomas. J ThrombHaemost 8: 221-227.
  13. Lima J (2011) Venous thromboembolism and gliomas: the need for increased vigilance. Clin J OncolNurs 15: 687-690.
  14. Smith TR, Lall RR, Graham RB, Mcclendon J Jr, Lall RR, et al. (2014) Venous thromboembolism in high grade glioma among surgical patients: results from a single center over a 10 year period. J Neurooncol 120: 347-352.
  15. Stein PD, Beemath A, Meyers FA, Skaf E, Sanchez J, et al. (2006) Incidence of venous thromboembolism in patients hospitalized with cancer. Am J Med 119: 60-68.
  16. Levitan N, Dowlati A, Remick SC, Tahsildar HI, Sivinski LD, et al. (1999) Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data. Medicine 78: 285-291.
  17. Smith TR, Nanney AD 3rd, Lall RR, Graham RB, McClendon J Jr, et al. (2015) Development of venous thromboembolism (VTE) in patients undergoing surgery for brain tumors: Results from a single center over a 10year period. J ClinNeurosci. 22: 519-525.
  18. Sørensen HT, Mellemkjaer L, Olsen JH, Baron JA (2000) Prognosis of cancers associated with venous thromboembolism. N Engl J Med 343: 1846-1850.
  19. Edwards RL RF (1984) Hemostatic Alterations in Cancer Patients. In: Honn KV LS, ed. Hemostatic Mechanism and Metastases. Boston: Nishoff, 342-354.
  20. LIEBERMAN JS, BORRERO J, URDANETA E, WRIGHT IS (1961) Thrombophlebitis and cancer. JAMA 177: 542-545.
  21. Rickles FR, Edwards RL (1983) Activation of blood coagulation in cancer: Trousseau's syndrome revisited. Blood 62: 14-31.
  22. Soong BC, Miller SP (1970) Coagulation disorders in cancer. 3. Fibrinolysis and inhibitors. Cancer 25: 867-874.
  23. Petterson TM, Marks RS, Ashrani AA, Bailey KR, Heit JA (2015) Risk of site-specific cancer in incident venous thromboembolism: A population-based study. Thromb Res 135: 472-478.
  24. Danish SF, Burnett MG, Stein SC (2004) Prophylaxis for deep venous thrombosis in patients with craniotomies: a review. Neurosurg Focus 17: E2.
  25. Valladares JB, Hankinson J (1980) Incidence of lower extremity deep vein thrombosis in neurosurgical patients. Neurosurgery 6: 138-141.
  26. Swann KW, Black PM (1984) Deep vein thrombosis and pulmonary emboli in neurosurgical patients: a review. J Neurosurg 61: 1055-1062.
  27. Voth D, Schwarz M, Hahn K, Dei-Anang K, al Butmeh S, et al. (1992) Prevention of deep vein thrombosis in neurosurgical patients: a prospective double-blind comparison of two prophylactic regimen. Neurosurg Rev 15: 289-294.
  28. Dhami MS, Bona RD, Calogero JA, Hellman RM (1993) Venous thromboembolism and high grade gliomas. ThrombHaemost 70: 393-396.
  29. Kniffin WD Jr, Baron JA, Barrett J, Birkmeyer JD, Anderson FA Jr (1994) The epidemiology of diagnosed pulmonary embolism and deep venous thrombosis in the elderly. Arch Intern Med 154: 861-866.
  30. Clagett GP, Anderson FA Jr, Geerts W, Heit JA, Knudson M, et al. (1998) Prevention of venous thromboembolism. Chest 114: 531S-560S.
  31. Attia J, Ray JG, Cook DJ, Douketis J, Ginsberg JS, et al. (2001) Deep vein thrombosis and its prevention in critically ill adults. Arch Intern Med 161: 1268-1279.
  32. Kurtoglu M, Yanar H, Bilsel Y, Guloglu R, Kizilirmak S, et al. (2004) Venous thromboembolism prophylaxis after head and spinal trauma: intermittent pneumatic compression devices versus low molecular weight heparin. World J Surg. 28: 807-811.
  33. Smith SF, Biggs MT, Sekhon LH (2005) Risk factors and prophylaxis for deep venous thrombosis in neurosurgery. SurgTechnolInt 14: 69-76.
  34. Geerts WH (2006) Prevention of venous thromboembolism in high-risk patients. Hematology Am SocHematolEduc Program .
  35. Cohen AT, Tapson VF, Bergmann JF, Goldhaber SZ, Kakkar AK, et al. (2008) Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet 371: 387-394.
  36. Scales DC, Riva-Cambrin J, Le TL, Pinto R, Cook DJ, et al. (2009) Prophylaxis against venous thromboembolism in neurointensive care patients: survey of Canadian practice. J Crit Care 24: 176-184.
  37. Zubkov AY, Wijdicks EF (2009) Deep venous thrombosis prophylaxis in cerebral hemorrhage. Rev Neurol Dis 6: 21-25.
  38. Barmparas G, Jain M, Mehrzadi D, Melo N, Chung R, et al. (2014) Aspirin increases the risk of venous thromboembolism in surgical patients. Am Surg 80: 920-925.
  39. Cerrato D, Ariano C, Fiacchino F (1978) Deep vein thrombosis and low-dose heparin prophylaxis in neurosurgical patients. J Neurosurg 49: 378-381.
  40. Tapaninaho A (1985) Deep vein thrombosis after aneurysm surgery. ActaNeurochir (Wien) 74: 18-20.
  41. Boström S, Holmgren E, Jonsson O, Lindberg S, Lindström B, et al. (1986) Post-operative thromboembolism in neurosurgery. A study on the prophylactic effect of calf muscle stimulation plus dextran compared to low-dose heparin. ActaNeurochir (Wien) 80: 83-89.
  42. Hamilton MG, Hull RD, Pineo GF (1994) Venous thromboembolism in neurosurgery and neurology patients: a review. Neurosurgery 34: 280-296.
  43. Geerts WH, Jay RM, Code KI, Chen E, Szalai JP, et al. (1996) A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med 335: 701-707.
  44. Nurmohamed MT, van Riel AM, Henkens CM, Koopman MM, Que GT, et al. (1996) Low molecular weight heparin and compression stockings in the prevention of venous thromboembolism in neurosurgery. ThrombHaemost 75: 233-238.
  45. Dickinson LD, Miller LD, Patel CP, Gupta SK (1998) Enoxaparin increases the incidence of postoperative intracranial hemorrhage when initiated preoperatively for deep venous thrombosis prophylaxis in patients with brain tumors. Neurosurgery 43: 1074-1081.
  46. Iorio A, Agnelli G (2000) Low-molecular-weight and unfractionated heparin for prevention of venous thromboembolism in neurosurgery: a meta-analysis. Arch Intern Med 160: 2327-2332.
  47. Cupitt JM (2001) Prophylaxis against thromboembolism in patients with traumatic brain injury: a survey of UK practice. Anaesthesia 56: 780-785.
  48. Deep K, Jigajinni MV, McLean AN, Fraser MH (2001) Prophylaxis of thromboembolism in spinal injuries--results of enoxaparin used in 276 patients. Spinal Cord 39: 88-91.
  49. Deep K, Jigajinni MV, Fraser MH, McLean AN (2002) Prophylaxis of thromboembolism in spinal injuries--survey of practice in spinal units in the British Isles. Injury 33: 353-355.
  50. Kleindienst A, Harvey HB, Mater E, Bronst J, Flack J, et al. (2003) Early antithrombotic prophylaxis with low molecular weight heparin in neurosurgery. ActaNeurochir (Wien) 145: 1085-1090.
  51. Agnelli G (2004) Prevention of venous thromboembolism in surgical patients. Circulation 110: IV4-12.
  52. Gerlach R, Raabe A, Beck J, Woszczyk A, Seifert V (2004) Postoperative nadroparin administration for prophylaxis of thromboembolic events is not associated with an increased risk of hemorrhage after spinal surgery. Eur Spine J. 13: 9-13.
  53. Raj D, Marshall RW (2008) Prophylaxis against thromboembolism in spinal surgery. Arch Orthop Trauma Surg 128: 1365-1371.
  54. Hoefnagel D, Kwee LE, van Putten EH, Kros JM, Dirven CM, et al. (2014) The incidence of postoperative thromboembolic complications following surgical resection of intracranial meningioma. A retrospective study of a large single center patient cohort. Clinical neurology and neurosurgery 123: 150-154.
  55. Wakefield TW, Myers DD, Henke PK (2008) Mechanisms of venous thrombosis and resolution. ArteriosclerThrombVascBiol 28: 387-391.
  56. Sevitt S (1973) The vascularisation of deep-vein thrombi and their fibrous residue: a post mortem angio-graphic study. J Pathol 111: 1-11.
  57. Brooks EG, Trotman W, Wadsworth MP, Taatjes DJ, Evans MF, et al. (2009) Valves of the deep venous system: an overlooked risk factor. Blood 114: 1276-1279.
  58. Bucek RA, Reiter M, Quehenberger P, Minar E (2002) C-reactive protein in the diagnosis of deep vein thrombosis. Br J Haematol 119: 385-389.
  59. Lyman GH, Bohlke K, Khorana AA, Kuderer NM, Lee AY, et al. (2015) Venous thromboembolism prophylaxis and treatment in patients with cancer: american society of clinical oncology clinical practice guideline update 2014. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 33: 654-656.
  60. Day JS, Ramsey ML, Lau E, Williams GR (2015) Risk of venous thromboembolism after shoulder arthroplasty in the Medicare population. J Shoulder Elbow Surg 24: 98-105.
  61. Christensen TD, Vad H, Pedersen S, Hvas AM, Wotton R, et al. (2014) Venous thromboembolism in patients undergoing operations for lung cancer: a systematic review. Ann ThoracSurg 97: 394-400.
  62. Sartori MT, Della Puppa A, Ballin A, Saggiorato G, Bernardi D, et al. (2011) Prothrombotic state in glioblastoma multiforme: an evaluation of the procoagulant activity of circulating microparticles. J Neurooncol 104: 225-231.
  63. Browd SR, Ragel BT, Davis GE, Scott AM, Skalabrin EJ, et al. (2004) Prophylaxis for deep venous thrombosis in neurosurgery: a review of the literature. Neurosurg Focus 17: E1.
  64. Khorana AA, Francis CW, Menzies KE, Wang JG, Hyrien O, et al. (2008) Plasma tissue factor may be predictive of venous thromboembolism in pancreatic cancer. J ThrombHaemost 6: 1983-1985.
  65. Bousquet Y (2012) Catalogue of Geadephaga (Coleoptera, Adephaga) of America, north of Mexico. Zookeys : 1-1722.
  66. Rolston JD, Han SJ, Bloch O, Parsa AT (2014) What clinical factors predict the incidence of deep venous thrombosis and pulmonary embolism in neurosurgical patients? J Neurosurg 121: 908-918.
  67. Stein PD, Hull RD, Kayali F, Ghali WA, Alshab AK, et al. (2004) Venous thromboembolism according to age: the impact of an aging population. Arch Intern Med 164: 2260-2265.
  68. Geerts WH, Heit JA, Clagett GP, Pineo GF, Colwell CW, et al. (2001) Prevention of venous thromboembolism. Chest 119: 132S-175S.
  69. Stein PD, Gottschalk A, Saltzman HA, Terrin ML (1991) Diagnosis of acute pulmonary embolism in the elderly. J Am CollCardiol 18: 1452-1457.
  70. Kokturk N, Oguzulgen IK, Demir N, Demirel K, Ekim N (2005) Differences in clinical presentation of pulmonary embolism in older vs younger patients. Circulation journal: official journal of the Japanese Circulation Society 69: 981-986.
  71. Le Gal G, Bounameaux H (2004) Diagnosing pulmonary embolism: running after the decreasing prevalence of cases among suspected patients. J ThrombHaemost 2: 1244-1246.
  72. Bajaj N, Bozarth AL, Guillot J, Kojokittah J, Appalaneni SR, et al. (2014) Clinical features in patients with pulmonary embolism at a community hospital: analysis of 4 years of data. J Thromb Thrombolysis 37: 287-292.
  73. Clagett GP, Reisch JS (1988) Prevention of venous thromboembolism in general surgical patients. Results of meta-analysis. Ann Surg 208: 227-240.
  74. Velmahos GC, Nigro J, Tatevossian R, Murray JA, Cornwell EE 3rd, et al. (1998) Inability of an aggressive policy of thromboprophylaxis to prevent deep venous thrombosis (DVT) in critically injured patients: are current methods of DVT prophylaxis insufficient? Journal of the American College of Surgeons 187: 529-533.
  75. Norwood SH, McAuley CE, Berne JD, Vallina VL, Kerns DB, et al. (2001) A potentially expanded role for enoxaparin in preventing venous thromboembolism in high risk blunt trauma patients. J Am CollSurg 192: 161-167.
  76. Simonneau G, Sors H, Charbonnier B, Page Y, Laaban JP, et al.(1997) A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. The THESEE Study Group. TinzaparineouHeparine Standard: Evaluations dansl'EmboliePulmonaire. N Engl J Med 337: 663-669.
  77. Kim J, Gearhart MM, Zurick A, Zuccarello M, James L, et al. (2002) Preliminary report on the safety of heparin for deep venous thrombosis prophylaxis after severe head injury. J Trauma 53: 38-42.
  78. [No authors listed] (1997) Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. The Columbus Investigators. N Engl J Med 337: 657-662.
  79. Agnelli G, Piovella F, Buoncristiani P, Severi P, Pini M, et al. (1998) Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery. N Engl J Med 339: 80-85.
  80. Vanek VW (1998) Meta-analysis of effectiveness of intermittent pneumatic compression devices with a comparison of thigh-high to knee-high sleeves. Am Surg 64: 1050-1058.
  81. Turpie AG, Hirsh J, Gent M, Julian D, Johnson J (1989) 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: 679-681.
  82. Zareba P, Wu C, Agzarian J, Rodriguez D, Kearon C (2014) Meta-analysis of randomized trials comparing combined compression and anticoagulation with either modality alone for prevention of venous thromboembolism after surgery. The British journal of surgery 101: 1053-1062.
  83. Lyman GH, Khorana AA, Falanga A, Clarke-Pearson D, Flowers C, et al. (2007) American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 25: 5490-5505.
  84. Carman TL, Kanner AA, Barnett GH, Deitcher SR (2003) Prevention of thromboembolism after neurosurgery for brain and spinal tumors. South Med J 96: 17-22.
Citation: Cote DJ, Smith TR (2015) Venous Thromboembolism in Brain Tumor Patients: A Review of Literature . J Hematol Thrombo Dis 3:196.

Copyright: © 2015 Cote DJ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.