Significance of von Willebrand factor in septic and nonseptic patients with acute lung injury.
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.
Ware
Lorraine B
LB
Division of Allergy, Pulmonary and Critical Care Medicine, T1217 MCN, Vanderbilt University School of Medicine, Nashville, TN 37232-2650, USA. lorraine.ware@vanderbilt.edu
Eisner
Mark D
MD
Thompson
B Taylor
BT
Parsons
Polly E
PE
Matthay
Michael A
MA
D018806:APACHE; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009102:Multiple Organ Failure / Q000209:etiology; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012121:Respiration, Artificial / Q000379:methods; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000209:etiology* / Q000401:mortality / Q000628:therapy; D018805:Sepsis / Q000150:complications*; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014841:von Willebrand Factor / Q000378:metabolism*
D015415:Biomarkers; D014841:von Willebrand Factor