Significance of von Willebrand factor in septic and nonseptic patients with acute lung injury

Am J Respir Crit Care Med. 2004 Oct 1;170(7):766-72. doi: 10.1164/rccm.200310-1434OC. Epub 2004 Jun 16.


Systemic endothelial activation and injury are important causes of multiorgan system failure. We hypothesized that plasma levels of von Willebrand factor (VWF), a marker of endothelial activation and injury, would be associated with clinical outcomes in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In 559 patients with ALI/ARDS enrolled in the National Heart, Lung, and Blood Institute ARDS Network trial of two VT strategies, plasma VWF levels were measured at randomization (mean 350 +/- 265% of normal control plasma) and Day 3 (344 +/- 207%). Baseline VWF levels were similar in patients with and without sepsis, and were significantly higher in nonsurvivors (435 +/- 333%) versus survivors (306 +/- 209%) even when controlling for severity of illness, sepsis, and ventilator strategy (increased odds ratio of death of 1.6 per SD size increase in VWF; 95% confidence interval, 1.4-2.1). Higher VWF levels were also significantly associated with fewer organ failure-free days. Ventilator strategy had no effect on VWF levels. In conclusion, the degree of endothelial activation and injury is strongly associated with outcomes in ALI/ARDS, regardless of the presence or absence of sepsis, and is not modulated by a protective ventilatory strategy. To improve outcomes further, new treatment strategies targeted at the endothelium should be investigated.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Female
  • Humans
  • Linear Models
  • Logistic Models
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Multiple Organ Failure / etiology
  • Multivariate Analysis
  • Predictive Value of Tests
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Respiration, Artificial / methods
  • Respiratory Distress Syndrome / blood*
  • Respiratory Distress Syndrome / etiology*
  • Respiratory Distress Syndrome / mortality
  • Respiratory Distress Syndrome / therapy
  • Sepsis / complications*
  • Survival Analysis
  • Systemic Inflammatory Response Syndrome / etiology
  • Time Factors
  • Treatment Outcome
  • United States / epidemiology
  • von Willebrand Factor / metabolism*


  • Biomarkers
  • von Willebrand Factor