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Published ahead of print on June 16, 2004, doi:10.1164/rccm.200310-1434OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 7, October 2004, 766-772

A more recent version of this article appeared on October 1, 2004
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Submitted on October 21, 2003
Accepted on June 15, 2004

Significance of von Willebrand Factor in Septic and Non-septic Patients with Acute Lung Injury

Lorraine B Ware1*, Mark D Eisner2, B. Taylor Thompson3, Polly Parsons4, Michael A Matthay5, and The Acute Respiratory Distress Syndrome Network

1 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA, 2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, CA, USA; Division of Occupational and Environmental Medicine, Department of Medicine, University of California, San Francisco, CA, USA, 3 Pulmonary/Critical Care Unit and ARDS Network Clinical Coordinating Center, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA, 4 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Fletcher Allen Health Care, University of Vermont, Burlington, VT, USA, 5 Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Francisco, CA, USA; Department of Anesthesia and Cardiovascular Research Institute, University of California, San Francisco, CA, USA

* To whom correspondence should be addressed. E-mail: lorraine.ware{at}vanderbilt.edu.

Systemic endothelial activation and injury are important causes of multi-organ 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 ALI/ARDS patients enrolled in the NHLBI ARDS Network trial of two tidal volume strategies, plasma VWF levels were measured at randomization (mean 350 ± 265% of normal controls) and day 3 (344 ± 207%). Baseline VWF levels were similar in patients with and without sepsis and were significantly higher in non-survivors (435 ± 333%) versus survivors (306 ±209 %) even when controlling for severity of illness, sepsis and ventilator strategy (increased OR of death of 1.6 per SD-size increase in VWF, 95% CI 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 further improve outcomes, new treatment strategies targeted at the endothelium should be investigated.
Key words: von Willebrand factor, ARDS, sepsis




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