Kivonat:
Introduction: Activation of inflammation and coagulation are
closely related and mutually interdependent in sepsis. The
acute-phase protein, plasminogen activator inhibitor-1 (PAI-1)
is a key element in the inhibition of fibrinolysis. Elevated
levels of PAI-1 have been related to worse outcome in pneumonia.
We aimed to evaluate the effect of functionally relevant 4G/5G
polymorphism of PAI-1 gene in pneumonia induced sepsis. Methods:
We enrolled 208 Caucasian patients with severe sepsis due to
pneumonia admitted to an intensive care unit (ICU). Patients
were followed up until ICU discharge or death. Clinical data
were collected prospectively and the PAI-1 4G/5G polymorphism
was genotyped by polymerase chain reaction-restriction fragment
length polymorphism technique. Patients were stratified
according to the occurrence of multiple organ dysfunction
syndrome, septic shock or death. Results: We found that carriers
of the PAI-1 4G/4G and 4G/5G genotypes have a 2.74-fold higher
risk for multiple organ dysfunction syndrome (odds ratio [OR]
95% confidence interval [CI] = 1.335 -5.604; p = 0.006) and a
2.57-fold higher risk for septic shock (OR 95% CI = 1.180 -
5.615; p = 0.018) than 5G/5G carriers. The multivariate logistic
regression analysis adjusted for independent predictors, such as
age, nosocomial pneumonia and positive microbiological culture
also supported that carriers of the 4G allele have a higher
prevalence of multiple organ dysfunction syndrome (adjusted odds
ratio [aOR] = 2.957; 95% CI = 1.306 -6.698; p = 0.009) and
septic shock (aOR = 2.603; 95% CI = 1.137 - 5.959; p = 0.024).
However, genotype and allele analyses have not shown any
significant difference regarding mortality in models non-
adjusted or adjusted for acute physiology and chronic health
evaluation (APACHE) II. Patients bearing the 4G allele had
higher disseminated intravascular coagulation (DIC) score at
admission (p = 0.007) than 5G/5G carriers. Moreover, in 4G
allele carriers the length of ICU stay of non-survivors was
longer (p = 0.091), fewer ventilation-free days (p = 0.008) and
days without septic shock (p = 0.095) were observed during the
first 28 days. Conclusions: In Caucasian patients with severe
sepsis due to pneumonia carriers of the 4G allele of PAI-1
polymorphism have higher risk for multiple organ dysfunction
syndrome and septic shock and in agreement they showed more
fulminant disease progression based on continuous clinical
variables.
