Venous thromboembolism: severe trauma: the role of prophylaxis is unclear

Clinical bottom line (level 2a-)

  1. Patients were severe trauma who received unfractionated heparin compared with no prophylaxis are not clearly less likely to have a DVT.
  2. Patients with severe trauma who received mechanical prophylaxis compared with no prophylaxis are not clearly less likely to develop a DVT.
  3. Patients who receive LMWH compared with unfractionated heparin are not clearly less likely to develop a PE.
  4. Patients who receive mechanical prophylaxis compared with unfractionated heparin are not clearly less likely to develop a DVT.
  5. The risk of developing venous thromboembolism is increased with
    • spinal cord injury
    • spinal fracture
    • increasing age
    • worsening injury
Velmahos et al: Agency for Healthcare Research and Quality 2000; 22 : -
Expires November 2003

The study

Systematic review of all studies of
  • Patients: with significant trauma
  • Intervention: LMWH, unfractionated heparin, mechanical prophylaxis compared with
  • Outcome: venous thromboembolism

    Articles found in all languages using Medline, Embase, Cochrane Controlled Trials Register, 1966 to January 1999 (search terms: detailed in text ) and and hand-searching reference lists of retrieved articles and relevant text books

    Selection criteria: by 2 independent reviewers
    Appraisal criteria: based on study design - Jada criteria used for controlled trials; otherwise critical-appraisal quality filters
    Articles excluded if:
    • elderly patients with a hip fracture
    • unable to distinguish patients with orthopaedic or neurological trauma from those having elective orthopaedic or neurosurgery
    • patient suffered only localised injury
    • burns patients
    • non-surgical patients


    73 studies found (19 RCTs, 17 comparative-cohort, 37 prospective or retrospective cohort) - 6 RCTs used in the meta-analysis
    • 4 RCTs involving 313 patients comparing unfractionated heparin with no prophlaxis
    • 3 RCTs involving 234 patients comparing mechanical prophylaxis with no prophylaxis
    • 4 studies involving 355 patients comparing LMWH with unfractionated heparin
    • 4 studies involving 620 patients comparing mechanical prophylaxis with unfractionated heparin

    Data was combined using a random-effects model. Studies were found to be significantly heterogeneous when comparing unfractionated heparin and control, mechanical prophylaxis and control, and LMWH and unfractionated heparin.

    The evidence

    Outcome Time to outcome CER OR
    (95% CI)    		 NN T
    (95% CI)
    unfractionated heparin v. control: DVT weeks 13/125
    (10.4%)    		 0.965
    (0.353 to 2.64)     		310
    (NNT = 15 to infinity;
    NNH = 8 to infinity)
    mechanical prophylaxis v. control: DVT weeks 7/141
    (5.0%)    		 0.769
    (0.265 to 2,24)     		91
    (NNT = 28 to infinity;
    NNH = 18 to infinity)
    unfractionated heparin v. LMWH: PE weeks 2/176
    (1.1%)    		 3.01
    (0.585 to 15.5)     		-45
    (NNT = 210 to infinity;
    NNH = 7 to infinity)
    unfractionated heparin v. mechanical prophylaxis: DVT weeks 34/427
    (8.0%)    		 1.61
    (0.495 to 2.72)     		23
    (NNT = 9 to infinity;
    NNH = 26 to infinity)

    • In cohort studies 0.2% of patients treated with a vena caval filter had a PE, compared with 0.7% without a filter. Studies were heterogeneous and the two groups could not be compared directly.
    • drug-related bleeding
      • unfractionated heparin: 4.1% (95% CI: 2.7% to 5.8%)
      • LMWH: 3.2% (95% CI: 1.8% to 4.7%)
    • drug-related thrombocytopenia
      • unfractionated heparin: 2.4% (95% CI: 1.1% to 3.8%)
      • LMWH: 0.49% (95% CI: 0.0% to 1.2%)

    Comments

    1. The incidence of DVT in a total of 12,527 patients was 12% (95% CI: 10% to 13%) and the incidence of PE in 22,336 patients was 1.5% (95% CI: 1.1% to 1.8%). These incidence rates were highly heterogeneous across the studies.
    2. Adding uncontrolled studies to the meta-analysis of mechanical prophylaxis v. no prophylaxis, or the meta-analysis of unfractionated heparin v. no prophylaxis did not alter the results.
    3. An increased risk of venous thromboembolism was associated with (univariate analysis)
      • spinal cord injury: OR 3.1 (95% CI: 1.8 to 5.4)
      • spinal fracture: OR 2.3 (95% CI: 1.4 to 3.6)
      • increasing age
      • worsening injury score
    4. The authors found few high-quality studies that dealt exclusively with patients who had significant trauma. In addition results were often heterogeneous meaning that few meaningful conclusions could be drawn. The meta-analyses have too few patients studied to be able to exclude an important clinical effect for the various interventions.

    Citation

    1. Velmahos GC, Kern J, Chan L, et al: Prevention of Venous Thromboembolism After Injury. Evidence Report/ Technology Assessment No. 22. (Prepared by Southern California Evidence-based Practice Center under Contract No. 290-97-0001.) AHRQ Publication No. 01-E004. Rockville, MD. Agency for Healthcare Research and Quality 2000; 22 : -
    Search Terms: from AHRQ website
    Contributor: Chris Ball, November 2001
    Reviewer:

    Clinical Question.
    Patient severe trauma
    Intervention or Exposure venous thromboembolism prophylaxis
    Comparison no prophylaxis
    Outcome venous thromboembolism
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