Significance of Von Willebrand Factor in Septic and Nonseptic Patients with Acute Lung Injury

• DOI: 10.1164/rccm.200310-1434oc
• Publication Date: 2004-06-17T00:34:28Z
• Authors: Lorraine B. Ware; Mark D. Eisner; B. Taylor Thompson; Polly E. Parsons; Michael A. Matthay
• Keywords: Male; Respiratory Distress Syndrome; Multiple Organ Failure; Middle Aged; Prognosis; Respiration, Artificial; Survival Analysis; 3. Good health; 03 medical and health sciences; Logistic Models; 0302 clinical medicine; Predictive Value of Tests; Case-Control Studies; Sepsis; Multivariate Analysis; Linear Models; Humans; Multicenter Studies as Topic; Female; Biomarkers; APACHE; Aged; Randomized Controlled Trials as Topic

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.