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Research Article Free access | 10.1172/JCI116529

Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock.

A A Creasey, A C Chang, L Feigen, T C Wün, F B Taylor Jr, and L B Hinshaw

Chiron Corporation, Emeryville, California 94608.

Find articles by Creasey, A. in: PubMed | Google Scholar

Chiron Corporation, Emeryville, California 94608.

Find articles by Chang, A. in: PubMed | Google Scholar

Chiron Corporation, Emeryville, California 94608.

Find articles by Feigen, L. in: PubMed | Google Scholar

Chiron Corporation, Emeryville, California 94608.

Find articles by Wün, T. in: PubMed | Google Scholar

Chiron Corporation, Emeryville, California 94608.

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Chiron Corporation, Emeryville, California 94608.

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Published June 1, 1993 - More info

Published in Volume 91, Issue 6 on June 1, 1993
J Clin Invest. 1993;91(6):2850–2860. https://doi.org/10.1172/JCI116529.
© 1993 The American Society for Clinical Investigation
Published June 1, 1993 - Version history
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Abstract

This study was designed to test the hypothesis that tissue factor pathway inhibitor (TFPI) plays a significant role in vivo in regulating coagulation that results from exposure of blood to tissue factor after vascular injury as in the case of gram negative sepsis. Highly purified recombinant TFPI (6 mg/kg) was administered either 30 min or 4 h after the start of a lethal intravenous Escherichia coli infusion in baboons. Early posttreatment of TFPI resulted in (a) permanent seven-day survivors (5/5) with significant improvement in quality of life, while the mean survival time for the controls (5/5) was 39.9 h (no survivors); and (b) significant attenuations of the coagulation response and various measures of cell injury, with significant reductions in pathology observed in E. coli sepsis target organs, including kidneys, adrenals, and lungs. TFPI administration did not affect the reduction in mean systemic arterial pressure, the increases in respiration and heart rate, or temperature changes associated with the bacterial infusion. TFPI treated E. coli infected baboons had significantly lower IL-6 levels than their phosphate buffered saline-treated controls, however tumor necrosis factor levels were similarly elevated in both groups. In contrast to the earlier 30-min treatment, the administration of TFPI at 4 h, i.e., 240 min, after the start of bacterial infusion resulted in prolongation of survival time, with 40% survival rate (2/5) and some attenuation of the coagulopathic response, especially in animals in which fibrinogen levels were above 10% of normal at the time of TFPI administration. Results provide evidence for the significance of tissue factor and tissue factor pathway inhibitor in bacterial sepsis, and suggest a role for blood coagulation in the regulation of the inflammatory response.

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Version history
  • Version 1 (June 1, 1993): No description

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