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von Willebrand factor antigen is an independent marker of poor outcome in patients with early acute lung injury

Ware, Lorraine B. MD; Conner, Edward R. MD; Matthay, Michael A. MD

CLINICAL INVESTIGATIONS
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Objective  The primary objective of this study was to test the hypothesis that the degree of systemic endothelial activation, as measured by the release of von Willebrand factor antigen into the circulation and pulmonary edema fluid, is an important determinant of outcome from acute lung injury and acute respiratory distress syndrome.

Design  Observational study.

Setting  Intensive care unit patients in a tertiary university hospital and a university-affiliated city hospital.

Patients  Fifty-one intubated, mechanically ventilated intensive care unit patients with acute lung injury or acute respiratory distress syndrome as defined by the North American European Consensus Conference definitions.

Interventions  Undiluted pulmonary edema fluid and plasma were collected within 1 hr of endotracheal intubation in all patients.

Measurements  von Willebrand factor antigen concentrations and protein concentration were measured in pulmonary edema fluid and in plasma.

Main Results  At the time of intubation, median plasma von Willebrand factor antigen was 251%, two-fold higher than the median pulmonary edema fluid von Willebrand factor antigen of 130%. Median edema fluid and plasma von Willebrand factor antigen concentrations were significantly higher in patients who did not survive hospitalization. Plasma von Willebrand factor antigen was also higher in those patients who had a longer duration of mechanical ventilation (as measured by ventilator-free days). Plasma von Willebrand factor antigen was also significantly higher in patients with sepsis and two or more organ system failures. According to stepwise logistic regression analysis, plasma von Willebrand factor antigen was independently associated with in hospital death. The positive predictive value for death if the plasma von Willebrand factor antigen concentration was >450% was 83%. A plasma von Willebrand factor antigen concentration of >450% previously has been shown to predict the development of acute respiratory distress syndrome.

Conclusions  These findings suggest that the degree of systemic endothelial activation and injury at the onset of acute lung injury is an important determinant of the outcome from acute lung injury.

From the Departments of Medicine and Anesthesia and the Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA.

Supported, in part, by grant HL51856 from the National Institutes of Health.

Address requests for reprints to: Michael A. Matthay, MD, CVRI Box 0130, University of California San Francisco, San Francisco, CA 94143-0130. E-mail: mmat@itsa.ucsf.edu

These findings suggest that the degree of systemic endothelial activation and injury at the onset of acute lung injury (ALI) is an important determinant of the ultimate outcome of ALI.

© 2001 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins