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

The fact that DVT and PE occur following trauma is incontrovertible. The optimal mode of prophylaxis has yet to be determined. Low dose heparin (LDH) given in doses of 5000 units subcutaneously two or three times daily represents one pharmacologic treatment modality used for prophylaxis against DVT/PE. A meta-analysis of 29 trials in over 8000 surgical patients demonstrated that LDH significantly decreased the incidence of DVT from 25.2%, in patients with no prophylaxis, to 8.7% in treated patients (p< 0.001). Similarly, PE was halved by LDH treatment (0.5% in treated patients compared to 1.2% in controls, p<0.001).In double-blind trials, the incidence of major hemorrhage was higher in treated patients (1.8%) than controls (0.8%) but this was not significant. Minor bleeding complications, such as wound hematomas, were more frequent in LDH treated patients (6.3%) compared to controls (4.1%, p<0.001).

Unfractionated LDH has not been shown to be particularly effective in preventing VTE in trauma patients. Three recent prospective trials demonstrated that LDH was not bet ter in preventing DVT than no prophylaxis in patients with an ISS of > 9. Sample sizes in these studies were small, and hence, a type II statistical error cannot be excluded. The results of LDH use in trauma, with regards to PE, are even more vague. We are aware of only two studies employing a combined modality of LDH and mechanical prophylaxis.

Defining the trauma patient who is at high risk for VTE is subjective, and this definition has been variable in the literature. The following injury patterns appear to differentiate high risk patients for VTE: severe closed head injury (GCS < 8), pelvis plus long bone fractures, multiple long bone fractures, and spinal cord injury. A group of trauma surgeons have developed a risk factor assessment tool for VTE and preliminary evidence supports it as a valid indicator of the development of VTE (Greenfield, EAST 1998). The various risk factors are weighted (Table 1), patients with a score of < 3 may be considered low risk, 3-5 is moderate risk, and > 5 is high risk.

II. Process

A Medline review from 1966 to the present, revealed several hundred articles related to the use of LDH in medical and general surgical patients. Only the 8 articles related to the use of LDH in trauma patients were utilized for the following recommendations.

III. Recommendations

A. Level I

There are insufficient data to support a standard on two subject.

B.Level II

There is little evidence to support a benefit of LDH as a sole agent for prophylaxis in the trauma patient at high risk for venous thromboembolism (VTE).

C. Level III

For patients in whom bleeding could exacerbate their injuries (such as those with intracranial hemorrhage, incomplete spinal cord injuries, intraocular injuries, severe pelvic or lower extremity injuries with traumatic hemorrhage, and intra-abdominal solid organ injuries being managed nonoperatively), the safety of LDH has not been established and an individual decision should be made when considering anticoagulant prophylaxis.

IV. Scientific Foundation

Heparin is a naturally occurring polysaccharide in varying molecular weight from 2,000-40,000.Low dose heparin augments the activity of antithrombin III, a potent, naturally occurring inhibitor of activated factor X (Xa) and thrombin, which produces interruption of both the intrinsic and extrinsic pathways.Low-dose heparin causes only minimal or no change in conventional clotting tests, such as the PTT.

A meta-analysis of 29 trials in over 8000 surgical patients demonstrated that LDH significantly decreased the incidence of DVT from 25.2%, in patients with no prophylaxis, to 8.7% in treated patients (p< 0.001).^[1] Similarly, PE was halved by LDH treatment; the incidence was 0.5% in treated patients compared to 1.2% in controls (p<0.001).^[1] In double-blind trials, the incidence of major hemorrhage was higher in treated patients (1.8%) than controls (0.8%) but this was not significant.^[1] Minor bleeding complications, such as wound hematomas, were more frequent in LDH treated patients (6.3%) compared to controls (4.1%, p<0.001).^[1]

Studies on the use of LDH in trauma patients are inconclusive. Shackford et al.^[2] in a nonrandomized, uncontrolled trial of 177 high risk trauma patients compared no prophylaxis (n=25), LDH (n=18), LDH + SCD (n=53), and SCD only (n=81) according to physician preference.There was no significant difference in VTE rate in the groups receiving no prophylaxis (4%) vs. those who received prophylaxis (LDH 6%; LDH + SCD 9%; SCD 6%). In a relatively large, nonrandomized, unblinded prospective study of 395 trauma patients admitted with an ISS > 9 who received either LDH, SCD, or no prophylaxis, Dennis et al.^[3] demonstrated a VTE rate of 3.2%, 2.7%, and 8.8%, respectively, with a hand-held Doppler flow probe.There was no statistically significant difference in VTE rate for the two types of prophylaxis, but there was a statistically significant difference in VTE in those who received prophylaxis vs. those who didn’t (p<0.02;X^[2] ). Specific analysis of those who received LDH vs. no prophylaxis revealed no significant difference in DVT rate.Ruiz et al.,^[4] in 100 consecutive trauma patients admitted to their trauma center with an ISS > 10, looked at the incidence of VTE according to type of prophylaxis received. In the 50 patients who received LDH, there was a DVT rate of 28% vs. a DVT rate of only 2%, in the 50 patients who received no prophylaxis. Closer scrutiny of this nonrandomized study revealed that the patients who received LDH were more severely injured (mean ISS 31 vs. 22) and had a longer period of immobilization (17.9 vs. 8.0 days), which certainly could have contributed to the higher DVT rate seen in the LDH prophylaxis group. Knudson et al.^[5] reported on 251 patients in a cohort study who received LDH, SCD, or no prophylaxis. They failed to show any effectiveness with prophylaxis in most trauma patients, except in the subgroup of patients with neurotrauma in which SCD was more effective than control in preventing DVT. Upchurch et al.^[6] compared 66 ICU-dependent trauma patients who received either no VTE prophylaxis or LDH. The groups were well matched according to age, ISS, length of stay, and mortality. There was no significance in VTE rate between the two groups. In this same study, the authors performed a meta-analysis of the current literature concerning the use of LDH in trauma patients.Five studies met their entry criteria for inclusion in the meta-analysis which included 1,102 patients.^{[2] [3] [4] [5]} This meta-analysis demonstrated no benefit of LDH as prophylaxis compared to no prophylaxis (10% vs.7%; P=0.771).Geerts et al.^[7] randomized 344 trauma patients to receive LMWH vs. LDH and found significantly fewer DVTs with LMWH than with LDH (31% vs. 44%, p=0.014 for all DVT; and 15% vs 6%, p=0.012 for proximal DVT). This study had no control group but, compared with the predicted DVT rate if the study patients had not received prophylaxis, the risk reduction for LDH was only 19% for DVT and only 12% for proximal DVT while the comparative risk reductions for LMWH were 43% and 65%, respectively. Napolitano et al.^[8] used a serial ultrasound screening protocol for DVT in 437 patients who were given four types of prophylaxis (LDH, VCB, LDH and VCB, no prophylaxis) according to their attending surgeon’s preference. There was no significant difference in DVT rate between groups (8.6%, 11.6%, 8.0%, 11.9% respectively).

Velmahos, et al^[9] looked at the ability of LDH and SCD or SCD alone in 200 critically injured patients who were then followed with biweekly Doppler exams to detect proximal lower extremity DVT. The incidence of DVT was 13% overall and not different between the two groups. The majority (58%) of DVT developed in the first two weeks. In a meta-analysis conducted under the auspices of the Agency for Healthcare Research and Quality, Velmahos and colleagues^[10] looked at all randomized controlled and non-randomized studies on the use of LDH in trauma patients. In the four randomized control studies on the use of LDH in trauma patients showed no difference in the incidence of DVT between those receiving LDH vs no prophylaxis (OR, 0.965; 95% CI, 0.360, 2.965) there was again no difference (OR 1.33; 95% CI, 0.360, 2.965). In summary, to date, LDH has very little proven efficacy, in and of itself in the prevention of VTE following trauma.

V. Summary

The overall effectiveness of LDH for prophylaxis of VTE in trauma patients remains unclear. Most studies show no effect of LDH on VTE. Most studies on the use of LDH in trauma patients suffer from severe methodologic errors, poor st udy design, and small sample size, suggesting the possibility of a type II statistical error.

VI. Future Investigation

There is enough accumulated data to warrant not using LDH in a trial in high risk trauma patients. Future studies should focus on the potential benefit of LDH in low risk trauma patients.

VII. References

1. Clagett GP, Reisch JS: Prevention of venous thromboembolism in general surgical patients: Results of a meta-analysis. Ann Surg 208:227-40, 1988
2. Shackford SR, Davis JW, Hollingsworth-Fridlund P, et al: Venous thromboembolism in patients with major trauma. Am J Surg 159:365-9, 1990
3. 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 35:132-9, 1993
4. Ruiz AJ, Hill SL, Berry RE: Heparin, deep venous thrombosis, and trauma patients. Am J Surg162:159­62, 1991
5. Knudson MM, Lewis FR, Clinton A, et al: Prevention of venous thromboembolism in trauma patients. J Trauma 37:480-7, 1994
6. Upchurch GR Jr, Demling RH, Davies J, et al: Efficacy of subcutaneous heparin in prevention of venous thromboembolic events in trauma patients. Am Surg 61:749-55, 1995
7. 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 335:701-7, 1996
8. Napolitano LM, Garlapati VS, Heard SO, et al: Asymptomatic deep venous thrombosis in the trauma patient: Is an aggressive screening protocol justified? J Trauma 39:651-9, 1995
9. 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 187:529-533, 1998.
10. Velmahos GC, Kern J, Chan L et al: Prevention of venous thromboembolism after injury: an evidence-based report-Part I: analysis of risk factors and evaluation of the role of vena cava filters. J Trauma 49:132-139,2000.

Table

Deep Venous Thrombosis (Dvt) in Trauma: A Literature Review

Low Dose Heparin