Venous Thromboembolism: Low Dose Heparin for DVT/PE Prophylaxis

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



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:

Statement of the Problem

The fact that DVT and pulmonary embolism (PE) occur after trauma is incontrovertible. The optimal mode of prophylaxis has yet to be determined. Low-dose heparin (LDH), given in doses of 5,000 units subcutaneously two or three times daily, represents one pharmacologic treatment modality for prophylaxis against DVT/PE.

In contrast, LDH has not been shown to be particularly effective in preventing VTE in trauma patients. Three recent prospective trials demonstrated that LDH was no better in preventing DVT than no prophylaxis at all in patients with an ISS > 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 regard to PE, are even more vague.


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 nine articles related to the use of LDH in trauma patients were used for the following recommendations (Table 2).


A. Level I: A Level I recommendation on this topic cannot be supported because of insufficient data.

B. Level II: Little evidence exist to support the benefit of LDH as a sole agent for prophylaxis in the trauma patient at high-risk for VTE.[3][7][10][14][20-22]

C. Level III: For patients in whom bleeding could exacerbate 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.

Scientific Foundation

Heparin is a naturally occurring polysaccharide varying in molecular weight from 2,000 to 40,000. LDH 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 partial thromboplastin time.

Studies on the use of LDH in trauma patients are inconclusive. In addition, many of these studies are single-institution studies with small sample sizes and lack randomization. These studies are summarized in Table 2.[7][20][21] Studies with larger sample sizes and randomization will be discussed herein.[3][5][10][14][17][22]

Knudson et al.[3] reported on 251 patients in a cohort study who received LDH, a pneumatic compression device (PCD), or no prophylaxis. These authors failed to show any effectiveness with prophylaxis in most trauma patients, except in the subgroup of patients with neurotrauma in which PCD was more effective in preventing DVT than control. Upchurch et al.[14] compared 66 intensive care unit (ICU)-dependent trauma patients who received either LDH or no VTE prophylaxis. No significance difference was seen in VTE rates between the two groups. In this same study, the authors performed a meta-analysis of the current literature concerning the use of LDH in 1,102 trauma patients. This meta-analysis demonstrated no benefit of LDH as prophylaxis compared with no prophylaxis (10% vs. 7%;p = 0.771). Geerts et al.[17] randomized 344 trauma patients to receive low-molecular-weight heparin (LMWH) or 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. However, when 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, whereas the comparative risk reductions for LMWH were 43% and 65%, respectively. Napolitano et al.[10] used a serial ultrasound screening protocol for DVT in 437 patients who were given four types of prophylaxis (LDH, PCD, LDH and PCD, and no prophylaxis) according to their attending surgeon's preference. No significant difference was seen in DVT rates between groups (8.6%, 11.6%, 8.0%, and 11.9%, respectively).

Velmahos et al.[5] looked at the use of LDH and PCD or PCD alone in 200 critically injured patients who were then followed with biweekly Doppler examinations to detect proximal lower extremity DVT. The incidence of DVT was 13% overall, and no difference was seen between the two groups. The majority (58%) of DVT developed in the first 2 weeks. In a meta-analysis conducted under the auspices of the Agency for Healthcare Research and Quality, Velmahos and colleagues[22] looked at all randomized controlled and nonrandomized studies on the use of LDH in trauma patients. The four randomized controlled studies on the use of LDH in trauma patients showed no difference in the incidence of DVT between those receiving LDH versus no prophylaxis (OR, 0.965; 95% CI, 0.360-2.965; vs. OR, 1.33; 95% CI, 0.360-2.965).


In summary, to date, LDH has very little proven efficacy in the prevention of VTE after trauma. Most studies on the use of LDH in trauma patients suffer from severe methodologic errors, poor study design, and small sample size, suggesting the possibility of a type II statistical error.

Future Investigation

Enough accumulated data do not exist to support the use of LDH in a trial in high-risk trauma patients. Future studies should focus on the potential benefit of more efficacious agents such as low-molecular-weight heparin.


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


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Lose-Dose Heparin

First Author

Year Reference Title Class Conclusion

Shackford SR


Venous thromboembolism in patients with major trauma. Am J Surg. 159:365–369


177 high-risk patients received LDH, PCD, LDH and PCD, or no prophylaxis. Nonrandomized, uncontrolled study. VTE rate: LDH, 6%; PCD, 6%; PCD and LDH, 9%; no prophylaxis, 4%. No difference in VTE rates between groups.

Dennis JW


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


Prospective, nonrandomized study of 395 patients with ISS > 9 received LDH, PCD, or no prophylaxis. VTE rate: LDH, 3.2%; PCD, 2.7%; no prophylaxis, 8.8%. Subgroup analysis revealed no significant difference in VTE rates between LDH and no prophylaxis. Some randomization problems with study.

Ruiz AJ


Heparin, deep venous thrombosis, and trauma patients. Am J Surg. 162:159–162


Nonrandomized study in which 100 consecutive patients received LDH or no prophylaxis. VTE rate: LDH, 28%; no propylaxis, 2%. LDH patients were more severely injured and at bed rest for a longer period.

Knudson MM


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


Randomized, prospective study of 251 patients receiving LDH, PCD or no prophylaxis. No significant benefit or VTE with prophylaxis. No significant benefit on VTE with prophylaxis except in the subgroup of neurotrauma patients in whom PCD seemed to offer protection.

Upchurch GR Jr


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


Meta-analysis on the use of LDH in 1,102 trauma patients revealed no significant benefit on VTE rate: LDH, 10%; no prophylaxis, 7% (p = 0.771).

Napolitano LM


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


437 screened for DVT, nonrandomized. VTE rate: LDH, 8.6%; PCD, 11.6%; LDH and PCD, 8.0%; no prophylaxis, 11.9%. No difference in VTE rates between groups.

Velamahos GC


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


Meta-analysis; 4 randomized control studies of LDH vs. no prophylaxis; no difference in DVT rate (OR, 0.965; 95% CI, 0.353–2.636).

Geerts WH


A comparison of low-dose heparin and low-molecular- weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med. 335:701–707


Randomized, double-blind, prospective trial in 334 trauma patients of LDH vs. LMWH. LMWH significantly decreased DVT rate (31% vs. 44% for LDH, p = 0.014).

Velamahos GC


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


200 critically injured patients received VT prophylaxis (LDH and/ or PCD) with weekly duplex; 26 developed proximal DVT (13%), 4 PE (2%). Risk factors were severe chest injuries; extremity fractures, high PEEP levels during mechanical ventilation.

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