Low-Molecular Weight Heparin for DVT Prophylaxis in Trauma
Abstract & Commentary
Synopsis: A large, double-blind, prospective trial comparing subcutaneous low-molecular-weight heparin (30 mg q12h) to standard low-dose heparin prophylaxis (5000 U q12h) reduced the incidence of venographically diagnosed venous thrombosis from 44% to 31% after major trauma.
Source: Geerts WH, et al. N Engl J Med 1996;335: 701-707.
In this study from the university of toronto, 344 consecutive patients with major trauma were entered to randomly receive either conventional heparin or low-molecular-weight heparin (LMH) every 12 hours subcutaneously beginning within 36 hours of injury and continuing up to 14 days. Asymptomatic patients were investigated with bilateral leg venograms to diagnose the presence and degree of deep venous thrombosis (DVT). Clinically apparent DVT or pulmonary embolism were evaluated with the usual diagnostic modalities including plethysmography, lung scans, and arteriograms. Patients with initial intracranial hemorrhage were excluded as were patients with traumatic foot amputations and those with uncontrolled hemorrhage at 36 hours. Significant bleeding was defined as requiring a 2 gm percent fall in hemoglobin, a two or more unit transfusion, or the need for surgical intervention to stop hemorrhage. Of the 344, 265 patients completed the study with adequate end point data for analysis.
Sixty of 136 patients (44.1%) in the heparin group and 40 of 129 patients (31%) in the LMH group developed DVT. Proximal DVT occurred in 15% of patients on heparin and 6% of patients receiving LMH. The severity of DVT was less in the LMH group. Those patients with leg fractures experienced the highest incidence of DVT but also demonstrated significant benefit with LMH (48.9% vs 38.8%).
Significant bleeding occurred in one patient in the heparin group and five patients receiving LMH; this difference did not reach statistical significance (P = 0.12). Other than discontinuing the treatment for one dose and transfusions in four patients, no complications from bleeding were significant.
COMMENT BY CHARLES G. DURBIN, Jr., MD, FCCM
This study confirms the high risk of DVT in patients following major trauma. From previous studies, this risk is estimated as high as 70%, greatest in patients with leg fractures and spinal cord injury. Despite conventional treatment with subcutaneous heparin, the incidence of DVT remains unacceptably high. Pulmonary embolism is the third most common cause of death in trauma victims surviving 24 hours or more. From studies of orthopedic surgery patients, the superiority of LMH over conventional prophylactic, low-dose heparin treatment has been shown. This study elegantly demonstrates that LMH is more effective than low-dose heparin in reducing the incidence of DVT in patients after major trauma with an acceptable increase in easily treated bleeding complications.
The cost of LMH was not considered in this study. It is at least 6-10 times more expensive than conventional heparin treatment. The costs of bleeding complications and increased length of stay should also be considered in a cost-effective analysis. The results of this study and others of LMH suggest that selective use in severely injured trauma patients is appropriate. Comparison of outcomes with other treatments remains to be performed.