Lilly et al 2014: Thrombosis prophylaxis and mortality risk

Journal Club 003

Authors: Aaron Paul
Chris Nickson

Lilly CM, et al. Thrombosis prophylaxis and mortality risk among critically ill adults. Chest. 2014 Jul 1;146(1):51-7. doi: 10.1378/chest.13-2160. PubMed PMID: 24722879. [Free Full Text]


In critically ill patients, how do we best manage the increased risk of venous thromboembolism (VTE)? Should we use prophylactic anticoagulation, mechanical devices, both or neither?



  • Observational cohort study


  • n = 294,896 adults over 271 geographically dispersed United States ICUs
  • All adult patients, discharged (alive or dead) from participating ICUs between Jan 2008 to October 2010

Inclusion criteria

  • all ICU adult patient stay >24hrs

Exclusion criteria

  • Patients who were ambulant, coagulopathic, fully anticoagulated or received a thrombin inhibitor during the first 24hrs of their ICU stay


  • Interventions:
    • VTE prophylactic anticoagulation
    • mechanical prevention (IVC filter, TED stockings and other calf compression devices)
    • both
    • neither
  • Comparisons were made between separately paired, propensity matched cohorts


Primary Outcome

  • Prophylactic anticoagulation was associated with a lower risk of death compared with those not provided VTE prophylaxis (after adjustment for propensity to receive VTE prophylaxis, APACHE IV scores and management with mechanical ventilation)
    • ICU mortality: hazard ratio 0.81 (95% CI 0.79 to 0.84, p<.0001)
    • hospital mortality: hazard ratio 0.84 (95% CI 0.82 to 0.86, p<.0001)

Secondary Outcomes

  • Mechanical devices, in comparison with no VTE prophylaxis, were not associated with a reduced mortality risk
  • Prophylactic anticoagulation was associated with a lower risk of death than those receiving only mechanical device prophylaxis (based on a study of 87,107 pairs of patients matched for propensity to receive VTE prophylaxis)
    • ICU sub-hazard ratio = 0.82 (95% CI 0.78 to 0.85; p < 0.001)
    • hospital sub-hazard ratio = 0.82 (95% CI 0.79 to 0.85; p < 0.001)


  • An inverse probability-weighted propensity score method was used to adjust for differences in selected risk factors among patients in the four alternative management groups (see Propensity Score Analysis in the LITFL CCC for a summary of this approach)
  • Good points include: large sample size, multi-centre study, treatment groups well matched, no identifiable conflicts of interest
  • Treatment groups were assigned based on clinical judgement, potential for bias from non-randomisation
  • the database used was based on electronic healthcare records (Philips eICU Research Institute data repository), which raises concerns about systematic bias related to data entry. However, the medical record was reviewed by an off-site team tasked with confirming that the approach was adherent to the JC/NQF ICU thromboprophylaxis measures an all drug orders were reviewed by a pharmacist.
  • Although less that 1% of the mechanical device group had IVC filters, it is questionable whether they should be grouped with TED stockings and other calf compression devices.
  • This data supports the findings of a previous Australasian study by Ho et al in 2011, which found an assocation betwen absent VTE prophylaxis in ICU patients and increased risk of mortality (OR, 1.07 vs 1.22).

Ho KM, Chavan S, Pilcher D. Omission of early thromboprophylaxis and mortality in critically ill patients: a multicenter registry study. Chest. 2011 Dec;140(6):1436-46. doi: 10.1378/chest.11-1444. Epub 2011 Sep 22. PubMed PMID: 21940768. [Free Full Text]


This study supports the use of VTE prophylaxis over no prophylaxis, and further supports a recommendation for prophylactic anticoagulation therapy in preference to mechanical device prophylaxis for critically ill adult patients who do not have a contraindication to anticoagulation.

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