title: Sustained high plasma plasminogen activator inhibitor-1 levels are associated with severity and mortality in septic patients.
abstract: BACKGROUND
  Higher plasma plasminogen activator inhibitor-1 (PAI-1) levels have been reported in septic patients. However, some questions remain unanswered, such as whether there is an association between plasma PAI-1 levels and sepsis severity and mortality, and inflammation state during the first week.
  
  
  METHODS
  Multicenter, observational and prospective study carried out in six Spanish Intensive Care Units of 260 patients with severe sepsis. Circulating levels of PAI-1 and tumour necrosis factor (TNF)-α were measured at day 1, 4 and 8. End-point was 30-day mortality.
  
  
  RESULTS
  Nonsurviving septic patients (n=89) presented higher PAI-1 levels than surviving (n=171) at day 1 (58.4 (33.3-83.8) vs 36.5 (21.1-62.5) ng/mL; p<0.001), 4 (34.0 (14.7-53.3) vs 16.2 (10.2-27.4) ng/mL; p<0.001) and 8 (30.6 (16.2-47.8) vs 18.9 (10.4-29.5) ng/mL; p=0.004). We found a positive correlation of PAI-1 levels with SOFA, lactic acid, aPTT, INR and TNF-α, and negative with platelet count at day 1, 4 and 8. Logistic regression analyses showed that PAI-1 levels at day 1 (p<0.001), 4 (p<0.001) and 8 (p=0.001) were associated with 30-day mortality. On ROC curve analysis to predict 30- day survival, the area under the curve of PAI-1 levels at day 1, 4 and 8 were 0.65 (95% CI=0.58-0.72; p<0.001), 0.69 (95% CI=0.60-0.78; p<0.001) and 0.65 (95% CI=0.54-0.75; p=0.005) respectively.
  
  
  CONCLUSIONS
  The most interesting findings of our study, to our knowledge the largest series reporting PAI-1 levels during follow-up in septic patients, were that plasma PAI-1 levels during the first week were associated with inflammation, severity and mortality.
authors.affiliation: Intensive Care Unit, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain. Electronic address: lorentemartin@msn.com.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Lorente
authors.affiliation: Intensive Care Unit. Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
authors.forename: María M
authors.initials: MM
authors.lastname: Martín
authors.affiliation: Laboratory Deparment, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Borreguero-León
authors.affiliation: Intensive Care Unit, Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Solé-Violán
authors.affiliation: Intensive Care Unit, Hospital Clínico Universitario de Valencia, Valencia, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Ferreres
authors.affiliation: Intensive Care Unit, Hospital San Jorge de Huesca, Huesca, Spain.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Labarta
authors.affiliation: Intensive Care Unit, Hospital Insular, Las Palmas de Gran Canaria, Spain.
authors.forename: César
authors.initials: C
authors.lastname: Díaz
authors.affiliation: Research Unit, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Jiménez
authors.affiliation: Atherosclerosis Research Laboratory, CIMA, University of Navarra, Pamplona, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Páramo
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1
keywords: Mortality; Outcome; PAI-1; Prognosis; Sepsis; Severity