Intensive Care Medicine

, Volume 33, Issue 8, pp 1354–1362

Increased mortality in septic shock with the 4G/4G genotype of plasminogen activator inhibitor 1 in patients of white descent

  • Gloria García-Segarra
  • Gerard Espinosa
  • Dolors Tassies
  • Josep Oriola
  • Jesús Aibar
  • Albert Bové
  • Pedro Castro
  • Joan-Carles Reverter
  • Josep-Maria Nicolás
Original

DOI: 10.1007/s00134-007-0695-y

Cite this article as:
García-Segarra, G., Espinosa, G., Tassies, D. et al. Intensive Care Med (2007) 33: 1354. doi:10.1007/s00134-007-0695-y

Abstract

Objective

To evaluate the effect of the 4G/5G PAI-1 gene polymorphism on the development of organ failure and outcome in critically ill patients with septic syndromes.

Design and setting

Prospective, observational study in a medical intensive care unit of a university hospital.

Patients

224 consecutively admitted patients.

Interventions

Epidemiological data, severity scores, and the primary site of infection were recorded. DNA genotyping of the PAI-1, TNF-β, and IL1-ra genes, and measurement of plasma PAI-1 antigen and D-dimer were carried out.

Measurements

The primary outcome variables were organ dysfunction and mortality.

Results

Eighty-eight subjects had septic shock at ICU entry or within 48 h from admission. Homozygotes for the 4G allele exhibited higher plasma concentrations of PAI-1 antigen and D-dimer than 4G/5G and 5G/5G subjects). ICU mortality was 44.0% in patients with 4G/4G, 23.4% in 4G/5G and 12.5% in 5G/5G, mainly due to multiorgan failure. After adjusting for SAPS II at admission the genotypes independently associated with ICU mortality in septic shock were TNF-B2/B2 (OR 2.83, 1.04–7.67) and 4G/4G of PAI-1 (OR 2.23, 1.02–4.85). The PAI-1 genotype did not determine susceptibility to infection or the outcome in nonseptic systemic inflammatory response syndrome, sepsis, severe sepsis, and nosocomial septic shock.

Conclusions

Homozygosity for 4G of the PAI-1 gene confers an increase in the risk of mortality in adult patients with septic shock due to a greater organ failure.

Keywords

Plasminogen activator inhibitor 1 Polymorphisms Septic shock Organ failure Fibrinolysis 

Supplementary material

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Gloria García-Segarra
    • 1
  • Gerard Espinosa
    • 1
  • Dolors Tassies
    • 2
  • Josep Oriola
    • 3
  • Jesús Aibar
    • 1
  • Albert Bové
    • 1
  • Pedro Castro
    • 1
  • Joan-Carles Reverter
    • 2
  • Josep-Maria Nicolás
    • 1
  1. 1.Medical Intensive Care Unit, Hospital Clinic, IDIBAPSUniversity of BarcelonaBarcelonaSpain
  2. 2.Department of Hemotherapy and Hemostasis, Hospital Clinic, IDIBAPSUniversity of BarcelonaBarcelonaSpain
  3. 3.Biochemistry Laboratory, Hospital Clinic, IDIBAPSUniversity of BarcelonaBarcelonaSpain