The tissue factor and plasminogen activator inhibitor type-1 response in pediatric sepsis-induced multiple organ failure.
OBJECTIVE
Cytokines increase endothelial tissue factor (TF) and tissue plasminogen activator inhibitor type-1 (PAI-1) expression in vitro. Tissue factor interacts with factor VII to facilitate thrombosis and PAI-1 inhibits fibrinolysis by endogenous plasminogen activators. Because cytokine release is increased in children with sepsis-induced multiple organ failure (MOF), we hypothesized a cytokine associated increase in circulating TF and PAI-1 antigen release, and systemic activity in these patients.


METHODS
One hundred and seven consecutive children, who met the criteria for sepsis, and 10 critically ill children without sepsis, were enrolled in the study. Plasma TF and PAI-1 antigen and activity levels, Interleukin-6 antigen levels (IL-6), nitrite + nitrate levels (marker of nitric oxide production) and number of organs failing were measured on days 1-3 of sepsis.


RESULTS
Increased TF and PAI-1 antigen, and PAI-1 activity levels were associated with increasing IL-6 and nitrite + nitrate levels (p <0.05), the development of MOF (p <0.05), and mortality (p <0.05). Increased systemic PAI-1 activity was associated with cardiovascular, renal. and hepatic failure (p <0.05). Increased systemic TF activity was associated with the development of coagulopathy (p <0.05) and tended to be associated with mortality (p = 0.06, power .77)


CONCLUSIONS
A shift to an anti-fibrinolytic endothelium phenotype characterizes children who develop sepsis-induced MOF and mortality. Children with coagulopathy have a shift to a pro-coagulant phenotype. These findings support potential therapeutic roles for PAI-1 and TF pathway inhibitors in reversal of this devastating pathophysiologic process.
Green
Jerril
J
Department of Anesthesiology and Critical Care Medicine and Pediatrics, University of Pittsburgh School of Medicine, Pennsylvania, USA.
Doughty
Lesley
L
Kaplan
Sandra S
SS
Sasser
Howell
H
Carcillo
Joseph A
JA
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000502:physiology*; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009102:Multiple Organ Failure / Q000097:blood* / Q000209:etiology / Q000401:mortality; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D010414:Pennsylvania / Q000453:epidemiology; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis* / Q000378:metabolism; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000150:complications; D019851:Thrombophilia / Q000097:blood / Q000209:etiology; D013925:Thromboplastin / Q000032:analysis*
D016207:Cytokines; D015850:Interleukin-6; D009566:Nitrates; D009573:Nitrites; D017395:Plasminogen Activator Inhibitor 1; D013925:Thromboplastin