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Byline: Gloria Garcia-Segarra (1), Gerard Espinosa (1), Dolors Tassies (2), Josep Oriola (3), Jesus Aibar (1), Albert Bove (1), Pedro Castro (1), Joan-Carles Reverter (2), Josep-Maria Nicolas (1) Keywords: Plasminogen activator inhibitor 1; Polymorphisms; Septic shock; Organ failure; Fibrinolysis 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-[beta], 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 48a-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 SAPSa-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. Author Affiliation: (1) Medical Intensive Care Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Villarroel 170, 08036, Barcelona, Spain (2) Department of Hemotherapy and Hemostasis, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain (3) Biochemistry Laboratory, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain Article History: Registration Date: 02/05/2007 Received Date: 10/04/2006 Accepted Date: 26/04/2007 Online Date: 31/05/2007 Article note: This research was supported by grants from Fondo de Instituciones Sanitarias (020533, 020696, 020711, and 050164). Electronic supplementary material The online version of this article (doi: 10.1007/s00134-007-0695-y) contains supplementary material, which is available to authorized users.