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Prevention of thromboembolism after neurosurgery for brain and spinal tumors. (Original Article).

Objective: Deep venous thrombosis (DVT) is a major cause of morbidity and mortality after surgery for primary and metastatic brain tumors.

Methods: We conducted a confidential survey of American neurosurgeons interested in tumor surgery to assess DVT risk awareness and thromboprophylaxis patterns.

Results: Of the 172 respondents, 108 (63%) underestimated the DVT risk after brain tumor surgery. After operating on patients who had brain or spinal tumors, 81.4 and 78.5% of respondents, respectively, reported using DVT prophylaxis. After performing brain tumor surgery, 76.2% of respondents reported using solely mechanical methods of prophylaxis "always" or "most of the time."

Conclusion: American neurosurgeons tend to underestimate the risk of DVT associated with brain tumor surgery and to use mechanical thromboprophylaxis despite the availability of effective pharmacologic anti-thrombotics. A better appreciation of the risk of thrombosis, combined with clinical studies to address safety, may enhance the use of prophylaxis and the perceived safety of antithrombotics in this setting.


Venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), are common, preventable perioperative complications that contribute to the morbidity and mortality of surgical patients. Neuro-oncology patients are at particular risk for venous thromboembolism (VT) due to the hypercoagulability associated with malignancy and invasive neurosurgical procedures, as well as risk factors such as prolonged anesthesia, paresis, and extended immobility. Venous thrombosis has been documented in 22 to 45% of patients operated on for brain tumors (Table 1). (1-4) Proximal DVT, commonly associated with PE, has been reported in 14 to 35% of cases. (1-4) Isolated calf vein thromboses, not commonly associated with PE, propagate and convert into more dangerous proximal DVT in as many as 35 to 40% of cases. (1,5) The substantial risk of DVT, combined with a PE-related mortality rate of 33 to 58% after brain tumor surgery, supports the need for aggressive prophylaxis against VT. (6-8)

The goal of prophylaxis against VT is to reduce the incidence of DVT and, by doing so, decrease the morbidity associated with the postthrombotic syndrome and the morbidity and mortality associated with PE. Acceptable means of prophylaxis must be not only effective but also demonstrably safe. Both mechanical and pharmacologic methods of prophylaxis are available and are used to varying degrees to prevent perioperative VT. While most general and orthopedic surgeons have shifted away from relying solely on mechanical methods of prophylaxis, and now use pharmacologic agents to a greater degree, many neurosurgeons have not modified their thromboprophylaxis strategies, presumably for safety reasons. Using a survey format, we sought to identify the current trends in perioperative VT prophylaxis used by practicing neurosurgeons and to investigate the relationship between VT risk awareness and the use of prophylaxis.


A confidential, voluntary 29-question survey (Appendix) was mailed to 590 U.S. neurosurgeons identified using the American Association of Neurological Surgeons (AANS) Tumor Section database. The survey was designed to assess DVT risk awareness and determine the current VT prophylaxis strategies used after adult brain tumor surgery, spinal tumor surgery, and stereotactic biopsy. Confidentiality was maintained by using AANS-assigned codes for each individual. Eight questions addressed physician demographics and training. Six of the questions designed to explore prophylaxis patterns and VT awareness required a written response. Seven used a modified Likert scale (answer choices were "always," "most of the time," "sometimes," "rarely," or "never"). The remaining eight questions were multiple choice and required the respondent to circle an answer. Respondents were instructed to return the completed survey by faxing it to the Cleveland Clinic Foundation Vascular Medicine research office. Approximately 2 to 3 weeks after the initial mailing, a second mailing was sent to individuals who had not responded. A database was created, and the results were analyzed with the use of GB-STAT software (Dynamic Microsystems, Inc., Silver Spring, MD).


A total of 190 surveys were returned, for a response rate of 32.2%. Eighteen responses were excluded from final analysis because of submission after a predetermined deadline (n = 4), blank survey (n = 1), physician practice other than neurosurgery (n = 4), pediatric neurosurgery practice (n = 3), retired physician (n = 5), and resident in training (n = 1). The results of 172 evaluable surveys were included in the final analysis. Of these 172 respondents, 143 (83.1%) stated that they were neurosurgery board-certified, and 27 (15.7%) of 172 stated that they had completed neuro-oncology fellowship training.

Of the 172 respondents, 41 (23.8%) correctly identified the risk of DVT after brain tumor surgery as being [less than or equal to]20%, while 71(41.3%) identified the risk as [greater than or equal to]9% (Fig. 1). Regarding the use of thromboprophylaxis, 81.4% of respondents indicated that they prescribe some form of DVT prophylaxis after brain tumor surgery "always" or "most of the time," and 78.5% responded similarly when asked about prophylaxis after spinal tumor surgery. Many respondents (52.9%) indicated that they "rarely" or "never" use prophylaxis after performing stereotactic biopsy (Fig. 2). Figure 3 shows the use of prophylaxis after brain tumor surgery performed by surgeons who reported performing fewer than 35 craniotomies yearly, 36 to 75 craniotomies yearly, and more than 75 craniotomies yearly. Pneumatic antiembolism stockings, with or without the addition of thromboembolism deterrence stockings, were used as the sole form of prophylaxis after brain tumor surgery by 131 (76.2%) of the respondent s "always" or "most of the time" and "rarely" or "never" by 13 (7.6%) of the respondents (Fig. 4). In contrast, low molecular weight heparin was used "always" or "most of the time" by only 10 respondents (5.8%) and "rarely" or "never" by 125 respondents (72.7%) (Fig. 3).

Figure 5 depicts the relationship between the perceived risk of DVT after brain tumor surgery and the use of prophylaxis. Of the 140 respondents who stated that they use prophylaxis "always" or "most of the time," 84 (60%) underestimated the actual risk of perioperative DVT after brain tumor surgery. Of the 17 respondents who indicated that they "rarely" or "never" use prophylaxis in patients who have had brain tumor surgery, 15 (88%) underestimated the risk of perioperative DVT. Within this group, 7 of the 17 respondents identified the risk as less than 1%, while an additional 8 respondents identified the risk as 1 to 9%.

When asked to indicate in a written response their preferred form of prophylaxis after brain tumor surgery, spinal tumor surgery, and stereotactic biopsy, respondents described a total of 20 different mechanical, pharmacologic, or combined methods. Figure 6 shows the distribution of preferred prophylaxis methods. A few respondents identified "no prophylaxis" as their preferred method after brain tumor surgery (n = 3) and spinal tumor surgery (n = 5), whereas 37.8% (n = 65) stated that they prefer to use nothing after stereotactic biopsy. In those who identified mechanical means of prophylaxis as their preferred method, pneumatic stockings were used alone or in combination with other mechanical modalities by 98 (95.1%) of 103, 88 (95.7%) of 92, and 58 (87.9%) of 66 for brain tumor surgery, spinal tumor surgery, and stereotactic biopsy, respectively. Low molecular weight heparin was the most frequently prescribed drug for prophylaxis (36%), followed in frequency by subcutaneous unfractionated heparin (31.9%), a spirin (9.9%), and warfarin (1.2%). When asked whether a bleeding complication in a patient receiving a particular pharmacologic agent would influence their future use of the same drug, 139 (81.3%) of 172 respondents answered affirmatively. In addition, 70.8% answered that such a bleeding complication would influence their use of other anticoagulant drugs as well.


The results from this survey reveal that despite recently published studies demonstrating the efficacy of pharmacologic prophylaxis against VT in postoperative neurosurgical patients, most U.S. neurosurgeons rely heavily on mechanical methods. Mechanical methods of prophylaxis may be preferred because of the perceived risk of bleeding with pharmacologic agents, a complication that is usually poorly tolerated by both surgeon and patient. The survey also reflects that many neurosurgeons underestimate the reported frequency of DVT after brain tumor surgery. This underestimation may contribute to the choice of prophylaxis.

The intensity of perioperative DVT prophylaxis recommended by the American College of Chest Physicians is based on the observed risk for VT in a particular setting or in a particular group of patients. Neurosurgical patients consistently fall into the highest risk category for perioperative VT. (9) The DVT incidence of 22 to 45% (Table 1) after brain tumor surgery (1-4) is comparable to the DVT incidence in orthopedic patients undergoing hip replacement surgery, a group much more readily recognized as being at high risk for VT and in need of aggressive prophylaxis. (9) A previous survey study of graduate surgical trainees showed that many general surgical residents underestimate the clinical risk of VT in postoperative patients. (10) This survey showed that the appropriate use of DVT prophylaxis was directly dependent on the correct estimate of risk. It is possible that the risk underestimation observed in our study affects the use of perioperative DVT prophylaxis in neuro-oncology, patients.

As suspected, our study group heavily favored mechanical methods of prophylaxis. Pneumatic stockings were the most frequently used mechanical means of prophylaxis, being used alone, in combination with other mechanical methods, or along with pharmacologic agents. Pneumatic stockings have been shown to decrease the absolute risk for postoperative DVT in neurosurgical patients by approximately 10 to 20%. (3,4,11,12) However, device malfunction and patient or nursing noncompliance may compromise their effectiveness. Although pneumatic stockings are safe, they may impede rehabilitation and walking.

Pharmacologic agents provide an ease of use and inpatient compliance benefit; however, their use is perceived to be complicated by an increased bleeding tendency. Recently, Agnelli et al (13) and others demonstrated the efficacy of subcutaneously administered heparin and the low molecular weight heparins dalteparin and enoxaparin for the prevention of VT in neurosurgical patients. (13-18) Agnelli et al (13) compared subcutaneous enoxaparin (40 mg/d beginning within 24 h of surgery) with control therapy consisting of compression stockings alone. They showed a significant decrease in DVT rate from 32% in the control patients to 17% in the enoxaparin-treated patients (P = 0.004). One study that compared subcutaneous enoxaparin 30 mg begun preoperatively and continued every 12 hours until discharge with the use of compression stockings alone, and combined compression/enoxaparin was terminated early because of an excessive rate of bleeding. (17) The results showed no difference in bleeding between the three groups ; however, limited enrollment prevented detection of a meaningful difference in safety. No study has adequately compared the efficacy of pneumatic stockings with that of a pharmacologic agent. In addition, no study of any means of prophylaxis has been performed with sufficient statistical power to address the issue of safety. A recent meta-analysis of controlled, randomized trials investigating low molecular weight heparin and unfractionated heparin in VT prophylaxis showed a 71% increase in relative risk for major bleeding compared with controls. However, the overall bleeding event rate was low--12 of 511 in treated patients and 7 of 511 in controls--and the absolute increase in bleeding risk was only 0.9%. (19)

The goal of VT prophylaxis is to decrease the incidence of DVT and PB and thus decrease the associated morbidity and mortality. In addition, prevention of VT will limit the number of perioperative patients in whom therapeutic anticoagulation is required to treat a thrombotic complication. Although several small studies and series have shown the safety of therapeutic intensity anticoagulation in neurosurgical patients, many practitioners facing a patient with postoperative DVT still rely on inferior vena cava (JVC) filters for PB prevention. (20-23) These filters are not without complications. The risk of recurrent DVT associated with IVC filters has been reported to be as high as 21%. (24,25) In addition, IVC filter placement does not eliminate the risk of recurrent PE. (24,25) Because no study reported to date has adequately evaluated the optimal treatment strategy for VT in neurosurgical patients, prevention should be the primary focus.

Whereas other survey formats have been used to evaluate the use of DVT prophylaxis in perioperative patients, this is the first survey of its kind of neurosurgeons who perform tumor surgery. Despite inherent flaws of the survey format of data collection, we think that this format allowed us to characterize the current practice patterns of selected neurosurgeons who perform tumor surgery. The results were similar to the practices within our own institution and were not unexpected. It is clear that for pharmacologic agents to gain use in DVT prevention in the neurosurgical population, additional studies must be performed. These studies should compare the currently used modalities of pneumatic stockings, with or without compression stockings, and pharmacologic agents. Most important, the studies should focus on the safety of the pharmacologic agents with respect to the risk of perioperative bleeding, particularly intracranial hemorrhage.


Many neurosurgeons underestimate the perioperative risk of DVT in patients with brain tumors. Mechanical methods of DVT prophylaxis are preferred among neurosurgeons. Bleeding is a significant concern that may limit the use of pharmacologic agents. Future trials of pharmacologic prophylaxis should use proper control groups and focus on safety as the primary trial endpoint.




Fig. 1

Respondents' perceived risk of deep venous thrombosis after brain tumor
surgery in the absence of prophylaxis. Solid bars represent the most
correct estimate of risk to the patient, 20 to 40%.

Perceived risk of DVT following BTS

 <1% 9.9
 1-9% 31.4
 10-19% 21.5
 20-29% 14.5
 30-40% 9.3
 No answer 13.4

Note: Table made from bar graph

Fig. 6

Respondents' indication of their preferred method of prophylaxis after
brain tumor surgery (BTS), spinal tumor surgery (STS), and stereotactic
biopsy (SB).

Preferred method of prophylaxis


Mechanical 59.9 53.4 38.4
Pharmacologic 16.9 17.4 6.4
Combined 17.4 19.8 2.3
None 1.7 2.9 37.8

Note: Table made from bar graph

Table 1.

Baseline incidence of deep venous thrombosis after brain tumor surgery

Series (ref. no.) Prophylaxis

Valladares et al, 1980 (2) None noted

Turpie et al, 1977 (3) IPC vs. no prophylaxis

Skillman et al, 1978 (4) IPC vs. no prophylaxis

Series (ref. no.) Diagnostic test

Valladares et al, 1980 (2) Fibrinogen [I.sup.125] scanning

Turpie et al, 1977 (3) Fibrinogen [I.sup.125] scanning

Skillman et al, 1978 (4) Fibrinogen [I.sup.125] scanning
 (venogram confirmed)

Series (ref. no.) Brain tumor surgery DVT (%)

Valladares et al, 1980 (2) 31 10 (32)
 16 malignant 4/16 (25)
 15 benign 6/15 (45)
Turpie et al, 1977 (3) 25 (IPC) 1/25 (4)
 27 (control) 6/21 (22)
Skillman et al, 1978 (4) 11 (IPC) 1/11 (9)
 20 (control) 7/20 (35)

(a) IPC, intermittent pneumatic compression

DVT, deep vein thrombosis.

Accepted April 23, 2002.


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(11.) 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 1989;149:679-681.

(12.) Black PM, Crowell RM, Abbott WM. External pneumatic calf compression reduces deep venous thrombosis in patients with ruptured intracranial aneurysms. Neurosurgery 1986;18:25-28.

(13.) Agnelli G, Piovella F, Buoncristiani P, et al. Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery. N Engl J Med 1998;339:80-85.

(14.) Bostrom S, Holmgren E, Jonsson O, et al. Post-operative thromboembolism in neurosurgery: A study on the prophylactic effect of calf muscle stimulation plus dextran compared to low-dose heparin. Acta Neurochir (Wien) 1986;80:83-89.

(15.) Cerrato D, Ariano C, Fiacehino F. Deep vein thrombosis and low-dose heparin prophylaxis in neurosurgical patients. J Neurosurg 1978;49:378-381.

(16.) Frim DM, Barker FG II, Poletti CE, et al. Postoperative low-dose heparm decreases thromboembolic complications in neurosurgical patients. Neurosurgery 1992;30:830-833.

(17.) Dickinson LD, Miller LD, Patel CP, Gupta SK. Enoxaparin increases the incidence of postoperative intracranial hemorrhage when initiated preoperatively for deep venous thrombosis prophylaxis in patients with brain tumors. Neurosurgery 1998;43:1074-1081.

(18.) Macdonald RL, Amidci C, Baron J, et al. Randomized, blinded, prospective comparison of dalteparin and low dose subcutaneous heparin for prevention of venous thromboembolic complications in patients undergoing craniotomy. Presented at the Congress of Neurological Surgeons 50th Annual Meeting, September 2000, San Antonio, TX.

(19.) Iorio A, Agnelli G. Low-molecular-weight and unfractionated heparin for prevention of venous thromboembolism in neurosurgery: A meta-analysis. Arch Intern Med 2000;160:2327-2332.

(20.) Ruff RL, Posner JB. Incidence and treatment of peripheral venous thrombosis in patients with glioma. Ann Neurol 1983;13:334-336.

(21.) Olin JW, Young JR, Graor RA, et al. Treatment of deep vein thrombosis and pulmonary emboli in patients with primary and metastatic brain tumors: Anticoagulants or inferior vena cava filter? Arch Intern Med 1987; 147:2177-2179.

(22.) Altschuler E, Moosa H, Selker RG, Vertosick FT Jr. The risk and efficacy of anticoagulant therapy in the treatment of thromboembolic complications in patients with primary malignant brain tumors. Neurosurgery 1990;27:74-77.

(23.) Schiff D, DeAngelis LM. Therapy of venous thromboembolism in patients with brain metastases. Cancer 1994;73:493-498.

(24.) Levin JM, Schiff D, Loeffler JS, et al. Complications of therapy for venous thromboembolic disease in patients with brain tumors. Neurology 1993;43:1111-1114.

(25.) Decousus H, Leizorovicz A, Parent F, et al. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis: Prevention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group. N Engl J Med 1998;338:409-415.


* Many of the surveyed neurosurgeons underestimated the incidence of perioperative deep venous thrombosis after brain tumor surgery.

* Most of the surveyed neurosurgeons use thromboprophylaxis after brain tumor and spinal tumor surgery but not typically after stereotactic biopsy.

* Many of the respondents prefer mechanical methods of prophylaxis after brain or spinal tumor surgery.

* Most of the identified forms of mechanical prophylaxis included pneumatic antiembolism stockings as one component of therapy.

From the Department of Cardiovascular Medicine, Section of Vascular Medicine; the Department of Neurosurgery, Brain Tumor Center; and the Department of Hematology and Medical Oncology, The Cleveland Clinic Foundation, Cleveland, OH. (Dr. Kanner is now with the Department of Neurosurgery, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.)

Reprint requests to Steven R. Deitcher, MD, Director, Section of Vascular Medicine, Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, 9500 Euclid Avenue/Desk S-60, Cleveland, OH 44195. Email:

Copyright [c] 2003 by The Southern Medical Association 0038-4348/03/9601-0017
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Author:Deitcher, Steven R.
Publication:Southern Medical Journal
Geographic Code:1USA
Date:Jan 1, 2003
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