Tissue factor pathway inhibitor and von Willebrand factor antigen levels in adult respiratory distress syndrome and in a primate model of sepsis

A. K. Sabharwal, S. P. Bajaj, A. Ameri, S. M. Tricomi, T. M. Hyers, T. E. Dahms, F. B. Taylor, M. S. Bajaj

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Abstract

Tissue factor pathway inhibitor (TFPI) is an anticoagulant protein primarily synthesized by the endothelium. A major fraction (~ 85%) of TFPI remains associated with the endothelium, whereas a small fraction (~ 15%) is secreted into the blood. In our attempts to search for a marker(s) of endothelial injury in the setting of adult respiratory distress syndrome (ARDS), we retrospectively measured plasma TFPI levels in patients at risk for and with ARDS caused by several etiologic factors. Plasma von Willebrand factor antigen (vWF-Ag), another endothelial-specific protein, was also measured in these patients. The mean plasma TFPI levels were slightly elevated (~ 1.3-fold), whereas vWF-Ag levels were significantly elevated (~ 3-fold) in the at-risk group as compared with those in the normal subjects. Both the TFPI (~ 1.8-fold) and the vWF-Ag (~ 4-fold) levels were further elevated in the ARDS group. Moreover, the sequential plasma samples from patients with ARDS had progressively increased levels of vWF-Ag and TFPI up to Days 4 and 8, respectively. Neither plasma vWF-Ag nor TFPI levels correlated with mortality in the at-risk group or the ARDS group. TFPI levels were also measured in bronchoalveolar lavage fluids (BALF). The levels (ng/ml) were: normal subjects, 0.05 ± 0.02 SE; at-risk group, 0.35 ± 0.16 SE; ARDS group, 0.99 ± 0.28 SE. Thus, the BALF TFPI levels were increased ~ 7-fold in the at-risk group and ~ 20-fold in the ARDS group relative to the value in the normal subjects. These findings indicate increased local synthesis of TFPI in the alveolar space both in the at-risk patients and in those with ARDS. In additional studies in a primate model of sepals, lethal doses (LD100) of E. coli administered to baboons resulted in a progressive increase in TFPI levels (~ 2-fold at 6 h), whereas sublethal doses caused only minimal increase (~ 1.2-fold). The vWF-Ag levels were elevated ~ 5- fold after infusion of LD100 concentrations of E. coli at 6 h and 4-fold after infusion of sublethal concentrations of E. coli at 24 h. Autopsies on animals in the LD100 group revealed pulmonary congestion, leukocyte infiltration, edema, and hemorrhage, all suggestive of acute lung injury. Thus, in the setting of acute lung injury plasma vWF-Ag appears to be considerably increased prior to significant damage to the endothelium, whereas increased plasma TFPI occurs only after severe injury. Increased levels of TFPI in BALF of at-risk patients and of those with ARDS appear to represent increased synthesis in the alveolar space rather than exudation of plasma TFPI.

Original languageEnglish (US)
Pages (from-to)758-767
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume151
Issue number3 I
StatePublished - Jan 1 1995
Externally publishedYes

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ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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