Venous Thromboembolism: Risk Factors After Injury

Published 2002
Citation: J Trauma. 53(1):142-164, July 2002.

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Authors

Rogers, Frederick B. MD; Cipolle, Mark D. MD, PhD; Velmahos, George MD, PhD; Rozycki, Grace MD; Luchette, Fred A. MD

Author Information

From the University of Vermont, Department of Surgery, Fletcher Allen Health Care (F.B.R.), Burlington, Vermont, Department of Surgery, Lehigh Valley Hospital (M.D.C.), Allentown, Pennsylvania, Department of Surgery, Division of Trauma and Critical Care, University of Southern California (G.V.), Los Angeles, California, Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, and Department of Surgery, Division of Trauma, Critical Care, and Burns, Loyola University Medical Center (F.A.L.), Maywood, Illinois.

Submitted for publication September 1, 2001.

Accepted for publication March 15, 2002.

Any reference in this guideline to a specific commercial product, process, or service by trade name, trademark, or manufacturer does not constitute or imply an endorsement, recommendation, or any favoritism by the authors or EAST. The views and opinions of the authors do not necessarily state or reflect those of EAST and shall not be used for advertising or product endorsement purposes.

Address for reprints: Frederick B. Rogers, MD, University of Vermont Department of Surgery, Fletcher Allen Health Care, 111 Colchester Avenue, Burlington, VT 05401; email: frederick.rogers@vtmednet.org.

Statement of the Problem

A number of factors have been reported to increase the risk of venous thromboembolism (VTE) after injury. Because VTE prophylaxis is associated with complications, it is essential to identify subgroups of trauma patients in whom the benefit of VTE prophylaxis will outweigh the risk of its administration. This is important because the benefits from the different methods of prophylaxis are still unclear when compared with no prophylaxis. Because the literature is inconsistent, a systematic review is needed to produce the best available evidence. Below, we describe the results of a meta-analysis of the existing literature. The reader needs to remember the limitations of meta-analysis. In addition, the fact that a risk factor was not identified as significant in meta-analysis does not mean that this factor must be ignored. Absence of proof does not equal proof of absence. It only means that enough evidence does not exist and that further studies of high quality are needed.

Process

Three literature databases were searched (MEDLINE, EMBASE, and Cochrane Controlled Trials Register) for articles reporting risk factors of VTE. All articles were reviewed by two independent reviewers and a third reviewer in cases of disagreement. The review was prepared against predetermined screening criteria, and the articles were given a numerical quality score. From an initial broad research that identified 4,093 relevant titles, 73 articles met all the inclusion criteria and were finally accepted for meta-analysis.

Pooled effect sizes (odds ratio [OR] and their 95% confidence intervals [CIs]) were estimated by the DerSimonian and Laird random-effects model. Shrinkage graphs were produced to display the effect size of each study and to compare with the overall model estimate. The heterogeneity among studies was tested by the Q statistic and p value for the χ2] test of heterogeneity. A level of significance at p < 0.05 was used for all comparisons.

To include a risk factor for meta-analysis, three or more studies reported on the risk factor. Risk factors identified only in one or two studies were not included. The risk factors identified were treated as either dichotomous or continuous variables as appropriate. For instance, if three or more studies provided data on the incidence of VTE in patients who were older or younger than 55 years old, then the risk factor was age > 55, a dichotomous variable. On the other hand, if three or more studies provided data on the age of patients with or without VTE by using only a mean and SD, the risk factor was simply age, a continuous variable (Table 1).

Recommendations

A. Level I: Patients with spinal cord injuries or spinal fractures are at high-risk for venous thromboembolism after trauma.[2-12]

B. Level II:

C. 1. Older age is an increased factor for venous thromboembolism, but it is not clear at what exact age the risk increases substantially.[4][5][9][11][13][14]

D. 2. Increasing Injury Severity Score (ISS) and blood transfusion appear to increase the risk of venous thromboembolism, but this association is still unclear.[3][5][8][9][14][15]

E. 3. Traditional risk factors such as long bone fractures,[3-6][9-13][15-17] pelvic fractures,[3-5][9-12][15][18] or head injuries,[3-9][15] although significantly associated with a high risk of venous thromboembolisms in single-institution studies, were not found to be powerful risk factors on meta-analysis.

Scientific Foundation

Risk factors As Dichotomous Variables

The following variables were reported in three or more studies and were included in the meta-analysis: gender,[3][13][18][19] head injury,[3-9][15] long bone fracture,[3-6][9-13][16][17][19] pelvic fracture,[3-5][9-12][15] spinal fracture,[3-12] and spinal cord injury.[4][9-12] A number of studies included age as a risk factor, but the different cut-off points used in each study (age > 30, 40, 50, 55, etc.) did not allow an analysis of this variable. The only risk factors found to place the patient at higher risk for development of deep venous thrombosis (DVT) were spinal fractures (OR, 2.260; 95%; CI, 1.415-3.610) and, even greater, spinal cord injury (OR, 3.017; 95% CI, 1.794-5.381). No significant heterogeneity was reported among studies on the different risk factors. Although long bone fractures were not found to bear statistical significance on meta-analysis, at least one high-quality study[17] with a valid regression model and an adequate sample size found long bone fractures to be a significant risk factor for venous thromboembolism.

Risk Factors As Continuous Variables

Three continuous variables (i.e., age,[5][9][11][13][14] ISS,[3][5][9][11][14][15] and units of blood transfused[3][14][15]) were reported in more than three studies and were included in the meta-analysis. Compared with patients without DVT, patients with DVT were significantly older (8.133 ± 1.504 [95% CI, 5.115-11.141]) years and had a significantly higher ISS (1.430 ± 0.747 [95% CI, 0.000-2.924]). The statistical difference in ISS was marginal, as shown by the lower limit of the 95% CI, and had minimal clinical significance. The difference of blood transfused between patients with and without DVT was not statistically significant (1.882 ± 2.815; 95% CI, -3.637-7.401), and no heterogeneity was reported among these studies.

Summary

The existing evidence supports the presence of two risk factors of posttraumatic VTE: spinal fractures and spinal cord injuries. Older age was an additional risk factor, but it was not clear at what exact age the risk increases substantially. Inadequate literature evidence exists to support that other frequently reported risk factors, such as long bone fractures, pelvic fractures, or head injuries, really increase the risk for VTE. However, a need exists for additional research in this area. In particular, adequate sized prospective studies should reevaluate the role of long bone fracture, pelvic fractures, head injuries, as well as specific age, blood transfusion, and ISS thresholds.

Future Investigation

Adequately sized studies should reevaluate the role of long bone fracture, pelvic fractures, and head injuries, as well as age, blood transfusion, and ISS thresholds and their association with the development of VTE after trauma. Large databases could be used to quantify risk using logistic regression profiles and could be the basis of specific prevention strategies.

Acknowledgment

We thank Jody Ciano for her help in the preparation of this article.

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Table

Studies Reporting on Risk Factors of Venous Thromboembolism in Trauma Patients 

First Author 

Year

Reference Title  Class Conclusion 

Knudson MM

1995

Prevention of venous thromboembolism in trauma patients J Trauma. 37:480–487

I

15 patients developed DVT (5.8%). Risk factors for DVT were age > 30 yr, immobilization > 3 days, pelvic and lower extremity fractures.

Kudsk KA

1994

Silent deep venous thrombosis in immobilized multiple trauma patients. Am J Surg. 158:515–519

II

39 multiple trauma patients received no prophylaxis, and had venography 7– 12 days after the injury. 24 developed DVT (61.5%) and 12 proximal DVT (31%). Risk factor for DVT was age.

Velmahos GC

1989

Inability of an aggressive policy of thromboprophylaxis to prevent deep venous thrombosis (DVT) in critically injured patients: are current methods of DVT prophylaxis insufficient? J Am Coll Surg. 187:529–533

II

200 critically injured patients received VTE prophylaxis (LDH and/or PCD), and had weekly Duplex scan. 26 developed proximal DVT (13%), 4 PE (2%). Risk factors for DVT were severe chest injuries, extremity fractures, and high levels of PEEP during mechanical support.

Spain DA

1998

Venous thromboembolism in the high-risk trauma patient: do risks justify aggressive screening and prophylaxis? J Trauma. 42: 463–469

III

280 high-risk trauma patients received prophylaxis, and were compared to 2,249 low-risk patients. 12 high-risk (5%) and 3 low-risk (0.1%) developed DVT. PE found only in 4 high-risk. Only patients with venous injuries were at higher risk for VTE.

Dennis J

1997

Efficacy of deep venous thrombosis prophylaxis in trauma patients and identification of high-risk groups. J Trauma. 35:132–139

II

395 trauma patients, 281 randomized to VTE prophylaxis and 113 to no prophylaxis, and screened by regular duplex. 18 (4.5%) developed DVT (8 with prophylaxis and 10 without) and 2 PE. Risk factor for VTE was spinal trauma.

Meyer CS

1993

Surveillance venous scans for deep venous thrombosis in multiple trauma patients. Ann Vasc Surg. 9:109–114

III

183 multiple trauma patients had VTE prophylaxis and irregular Duplex screening. 22 (12%) developed DVT. Risk factors for DVT were spinal injuries and symptoms of DVT.

Piotrowski JJ

1995

Is deep vein thrombosis surveillance warranted in high-risk patients? Am J Surg. 172:210– 213

II

343 high-risk trauma patients had VTE prophylaxis and were screened by duplex. 20 developed DVT (5.8%) and 3 PE (1%). Independent risk factors for DVT were age and GCS score.

Napolitano LM

1996

Asymptomatic deep venous thrombosis in the trauma patient: is an aggressive screening protocol justified? J Trauma. 39:651–659

III

458 trauma patients had VTE prophylaxis and regular Duplex scan. 45 (10%) developed DVT and 1 PE. Independent risk factors of DVT were age, ISS, RTS, length of stay, and spinal injury.

Geerts WH

1995

A prospective study of venous thromboembolism after major trauma. N Engl J Med. 331:1601–1606

II

349 major trauma patients with venographic assessment 14–21 days after admission. 201 (57.6%) developed DVT and 63 (18%) proximal DVT. Independent risk factors of DVT were age, blood transfusion, surgery, fracture of femur of tibia, and spinal cord injury.

Knudson MM

1994

Use of low molecular weight heparin in preventing thromboembolism in trauma patients. J Trauma. 41:446–459

I

487 trauma patients stratified to receive LMWH or PCD, and had regular duplex. DVT was found only in 2.4% patients. Risk factors for DVT were immobilization > 3 days, age > 30 yr, and lower extremity or pelvic fractures.

Abelseth G

1996

Incidence of deep vein thrombosis in patients with fractures of the lower extremity distal to the hip. J Orthop Trauma. 10:230–235

II

102 patients with lower extremity fractures, receiving no prophylaxis, had venography after operative fixation. 253 major trauma patients randomized to PCD, LDH, or no prophylaxis and followed by regular duplex. 29 developed DVT (28%) and 2 PE. Risk factors for DVT were age > 60, OR time > 105 min, and time from injury to operation > 27 h.

Upchurch GR Jr

1996

Efficacy of subcutaneous heparin in prevention of venous thromboembolic events in trauma patients. Am Surg. 61:749–755

III

66 trauma patients received VTE prophylaxis and irregular duplex scan. 13 (19.6%) developed DVT and 3 (4.5%) PE. Risk factors for VTE were older age and head, spinal cord, pelvic, and lower extremity trauma.

Knudson MM

1992

Thromboembolism following multiple trauma. J Trauma. 32:2–11

II

113 multiple trauma patients randomized to PCD or LHD, and screened by regular Duplex scan. 12 (10.6%) developed VTE (5 DVT, 4 PE, 3 both), 9 in the PCD group and 3 in the LDH. Risk factors for VTE were age, immobilization, number of transfusions, and clotting abnormalities.

Hill SL

1994

Deep venous thrombosis in the trauma patient. Am Surg. 60:405–408

II

100 trauma patients. 50 received LDH and 50 did not nonrandomly, and had regular duplex screening. 15 developed DVT, 14 of them without prophylaxis. Risk factors were lower extremity injuries and a higher ISS.

Geerts WH

1996

A comparison of low-dose heparin with low-molecular weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med. 335:701–770

I

265 major trauma patients randomized to LDH or LMWH, and had venography 10–14 days after admission. 60 (44%) LDH and 40 (31%) LMWH patients developed DVT. Proximal DVT in 15% and 6%, respectively. The incidence of DVT was higher in patients with leg fractures.

Waring W

1991

Acute spinal cord injury and the incidence of clinically occurring thromoembolic disease. Paraplegia. 29:8–16

III

DVT developed in 14.5% and PE in 4.6%. Age was the only significant factor for PE. 1,419 spinal cord injury patients included and followed for development of VTE. Stratification according to age, gender, level, and type of injury.

Spannagel U

1993

Low molecular weight heparin for the prevention of thromboembolism in outpatients immobilized by plaster cast. Semin Thromb Hemost. 19 (suppl 1): 131–141

I

DVT developed in 27 (10.6%), 21 from the no-prophylaxis group and 6 from LMWH. Risk factors for DVT were age > 30 yr, obesity, varicose veins, and fractures. 306 patients included, 257 analyzed; 127 randomized to receive no prophylaxis and 126 to LMWH.

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