Venous Thromboembolism: Risk Factors After Injury--old

Archived PMG

Published 1998
Citation: J Trauma. 53(1):142-164, July 2002.

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Authors

EAST Practice Parameter Workgroup for DVT Prophylaxis

Frederick B. Rogers, MD, FACS
University of Vermont Department of Surgery
Director of Trauma and Critical Care
Fletcher Allen Heath Care
Burlington, VT

Mark D. Cipolle, MD, Ph.D.
Surgical Practice Center
Allentown, PA

George Velmahos, MD, Ph.D.
Department of Surgery, Division of Trauma and Critical Care
University of Southern California
Los Angeles, CA

Grace Rozycki, MD
Emory USM, Department of Surgery
Atlanta, GA

I. Statement of the Problem

A number of factors have been reported to increase the risk for 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 concept becomes even more important, as the benefit from the different methods of prophylaxis is still unclear when compared to no prophylaxis. Because the literature is inconsistent, a systematic review is needed to produce the best available evidence.

II. Process

Three literature databases were searched (MEDLINE, EMBASE, and Cochrane Controlled Trials Register) for articles reporting on risk factors of VTE. All articles were reviewed by two independent reviewers and a third reviewer in cases of disagreement. The review was done 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 ration [OR] and their 95% confidence intervals [CI]) were estimated by the DerSimonian and Laird random-effects model. Shrinkage graphs were produced to display the effect size of each study and compare it with the overall model estimate. The heterogeneity among studies was tested by the Q-statistic and P value for the chi-square test of heterogeneity. A level of significance at P < 0.05 was used for all comparisons.

In order to include a risk factor for meta-analysis, three or more studies should have 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 standard deviation, the risk factor was simply “age”, a continuous variable.

III. Recommendations

A. Level I

Patients with spinal cord injuries or spinal fractures are at high risk for venous thromboembolism following trauma.

B. Level II

1 Older age is an increased factor for venous thromboembolism but it is not clear at which exact age the risk increases substantially.

2 Increasing ISS and blood transfusion do appear to be associated with a high risk of venous thromboembolism in single institution studies, however, on meta-analysis these factors did not prove of major significance.

3 Likewise traditional risk factors such as long bone fractures, pelvic fractures or head injuries in many studies may constitutes a high risk patient population in single institution studies but on meta-analysis it did not prove of major significance.

IV. Scientific Foundation

Risk factors as dichotomous variables

The following variables were reported in 3 or more studies and for this reason included in the meta­analysis: gender,[1-4] head injury,[3] [5-11] long-bone fracture,[3-8] [11-16] pelvic fracture,[3] [5] [6] [8] [11] [12] [14] [16] spinal fracture,[3] [5-7] [9-12] [14] [16] and spinal cord injury.[5] [11] [12] [14] [16]A number of studies included age as a risk factor, but the different cut­off points used in each study (age > 30, 40, 50, 55, etc.) did not allow analysis of this variable. The only risk factors found to place the patient at higher risk for development of DVT were spinal fractures (OR: 2.260, 95%

CI: 1.415, 3.610) and even more spinal-cord injury (OR: 3.017, 95% CI: 1.794, 5.381). There was no significant heterogeneity among studies reporting on the different risk factors.

Risk factors as continuous variables

Three continuous variables, i.e. age,[4-6] [11] [14] [17] injury severity score (ISS),[3] [6] [8] [11] [14] [17] and units of blood transfused,[3] [8] [17] were reported in more than 3 studies and for this reason included in the meta-analysis. Compared to patients without deep venous thrombosis (DVT), patients with DVT were significantly older by

8.133+1.504 (95% CI: 5.115, 11.141) years and had a significantly higher ISS by 1.430+0.747 (95% CI: 0.000, 2.924). This statistical difference in ISS was marginal, as shown by the lower limit of the 95% CI, and has minimal clinical significance. The difference in the amount of blood transfused between patients with and without DVT was not statistically significant (1.882+2.815, 95% CI: -3.637, 7.401). There was no heterogeneity among these studies.

V. Summary

The existing evidence supports the presence of two risk factors of post-traumatic VTE: spinal fractures and spinal cord injuries. Older age is an additional risk factor but it is not clear at which exact age the risk increases substantially. There is inadequate literature evidence to support that other frequently reported risk factors, such as long-bone fractures, pelvic fractures or head injuries, really increase the risk for VTE. There is a need for additional research in this area.

VI. Future Investigation

VII. References

  1. Waring WP, Karunas RS. Acute spinal cord injury and the incidence of clinically occurring thromboembolic disease. Paraplegia 1991;29:8-16.
  2. Spannagel U, Kujath P. Low molecular weight heparin for the prevention of thromboembolism in outpatients immobilized by plaster cast. Semin Thromb Hemost 1993;19 (suppl 1);131-41.
  3. Knudson MM, Lewis FR, Clinton A, et al. Prevention of venous thromboembolism in trauma patients. J Trauma 1994;37:480-7.
  4. Abelseth G, Buckley RE, Pineo GE, et al. Incidence of deep vein thrombosis in patients with fractures of the lower extremity distal to the hip. J Orthop Trauma 1996;10:230-5.
  5. Kudsk KA, Fabian T, Baum S, et al. Silent deep venous thrombosis in immobilized multiple trauma patients. Am J Surg 1989;158:515-9.
  6. Velmahos GC, Nigro J, Tatevossian R, et al. 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 1998;187:529-33.
  7. Spain DA, Richardson JD, Polk JR, et al. Venous thromboembolism in the high-risk trauma patient: do risks justify aggressive screening and prophylaxis? J Trauma 1997;42:463-9.
  8. Knudson MM, Collins JA, Goodman SB, et al. Thromboembolism following multiple trauma. J Trauma 1992;32:2-11.
  9. Dennis JW, Menawat S, Von Thron J, et al. Efficacy of deep venous thrombosis prophylaxis in trauma patients and identification of high-risk groups. J Trauma 1993;35:132-9.
  10. Meyer CS, Blebea J, Davis K, Jr, Fowl R, Kempsczinski RF. Surveillance venous scans for deep venous thrombosis in multiple trauma patients. Ann Vasc Surg 1995;9:109-14.
  11. Piotrowski JJ, Alexander JJ, Brandt CP, et al. Is deep vein thrombosis surveillance warranted in high-risk patients? Am J Surg 1996;172:210-3.
  12. Napolitano LM, Garlapati VS, Heard SO, et al. Asymptomatic deep venous thrombosis in the trauma patient: is an aggressive screening protocol justified? J Trauma 1995;39:651-9.
  13. Hill SL, Berry RE, Ruiz AJ. Deep venous thrombosis in the trauma patient. Am Surg1994;60:405-8.
  14. Geerts WH, Code KJ, Jay RM, et al. A prospective study of venous thromboembolism after major trauma. N Engl J Med 1994;331:1601-6.
  15. Geerts WH, Jay RM, Code KI, et al. A comparison of low-dose heparin with low-molecular weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med 1996;335:701-7.
  16. Knudson MM, Morabito D, Paiement GD, et al. Use of low molecular weight heparin in preventing thromboembolism in trauma patients. J Trauma 1996;41:446-59.
  17. Upchurch GR, Jr, Demling RH, Davies J, et al. Efficacy of subcutaneous heparin in prevention of venous thromboembolic events in trauma patients. Am Surg 1995;61:749-55.

Table 

Evidence Table. Studies reporting on risk factors of venous thromboembolism in trauma patients.

First Author Year Reference Title Class Conclusions

Waring W et al1

1991

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

III

DVT developed in 14.5% and PE in 4.6%. Age was the only significant factor for PE. 1419 spinal cord injury patients included and followed for development of VTE. Stratification according to age, gender, level and type of injury.

Spannagel U et al2

1993

Low molecular weight hepar in for the prevention of thromboembolism in outpatients immobilized by plaster cast.

Semin Thromb Hemost 19 (suppl 1). 131-41

I

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

Knudson MM et al3

1994

Prevention of venous thromboembolism in trauma patients.

J Trauma. 37:480-7

I

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

Abelseth G et al4

1996

Incidence of deep vein thrombosis in patients with fractures of the lower extremity distal to the hip.

J Orthop Trauma10:230-5

II

102 patients with lower extremity fractures, receiving no prophylaxis, had venography after operative fixation. 253 major trauma patients randomized to SCD, 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 minutes, and time from injury to operation >27 hours.

Kudsk KA et al5

1989

Silent deep venous thrombosis in immobilized multiple trauma patients.

Am J Surg158:515-9

II

39 multiple trauma patients included, rece ived 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 et al6

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?

J Am Coll Surg187:529-33

II

200 critically injured patients included, received VTE prophylaxis (LDH and/or SCD), 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 et al7

1997

Venous thromboembolism in the high -risk trauma patient: do risks justify aggres sive screening and prophylaxis?

J Trauma42:463-9

III

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

Knudson MM et al8

1992

Thromboembolism following multiple trauma.

J Trauma32:2-11

II

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

Dennis JW et al9

1993

Efficacy of deep venous thrombosis prophylaxis in trauma patients and identification of high-risk groups.

J Trauma35:132-9.

II

395 trauma patients included, 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 withou t) and 2 PE. Risk factor for VTE was spinal trauma.

Meyer CS et al10

1995

Surveillance venous scans for deep venous thrombosis in multiple trauma patients.

Ann Vasc Surg9:109-14

III

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

Piotrowski JJ et al11

1996

Is deep vein thrombosis surveillance warranted in high -risk patients?

Am J Surg172:210-3

II

343 high -risk trauma patients included, 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.

Napolitano LM et al12

1995

Asymptomatic deep venous thrombosis in the trauma patient: is an a ggressive screening protocol justified?

J Trauma39:651-9

III

458 trauma patients included, 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 inju ry.

Hill SL et al13

1994

Deep venous thrombosis in the trauma patient.

Am Surg60:405-8

II

100 trauma patients included, 50 received LDH and 50 did not non -randomly, 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 et al14

1994

A prospective study of venous thromboembolism after major trauma.

N Engl J Med331:1601-6

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 or tibia, and spinal cord injury.

Geerts et al15

1996

A comparison of low-dose heparin with low-molecular weight heparin as prophylaxis against venous thromboembolism after major trauma.

N Engl J Med335:701-7

I

265 major trauma patients included, 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.

Knudson MM et al16

1996

Use of low molecular weight heparin in preventing thromboembolism in trauma patients.

J Trauma41:446-59

I

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

Upchurch GR, Jr et al17

1995

Efficacy of subcutaneous heparin in prevention of venous thromboembolic events in trauma patients.

Am Surg61:749-55

III

66 trauma patients included, 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.

VTE: venous thromboembolism

DVT: deep venous thrombosis

PE: pulmonary embolism

LDH: low-dose heparin

LMWH: low-molecular weight heparin

SCD: sequential compression device

OR: operating room

PEEP: positive end -expiratory pressure

GCS: Glasgow Coma Scale

ISS: injury severity score

RTS: revised trauma score

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