Biomarkers in sepsis at time zero: intensive care unit scores, plasma measurements and polymorphisms in Argentina

Abstract

Introduction: A patient's response to sepsis is influenced by their genetic background. Our objective was to use plasma markers, such as protein C (PC), D-dimer, Plasminogen Activator Inhibitor-1 (PAI-1) levels, and the PAI-1 rs1799889 4G/5G and Tumor Necrosis Factor-α rs1800629 G/A polymorphisms to improve classical intensive care unit (ICU) scores. Methodology: We studied 380 subjects, 166 with sepsis. We performed coagulation tests: plasma PAI-1 and PC levels were evaluated by chromogenic methods; and D-dimer was evaluated by immunoturbidimetric assay. Polymorphisms were performed using for polymerase chain reactions followed by digest with specific restriction enzyme. We acquired the APACHE and SOFA scores (time zero), sex, age, body mass index, associated co-morbidities, length of ICU stay (days), the severity of sepsis (sepsis, severe sepsis or septic shock), the HIV status and the ICU outcome (survival or death). Results: We found significant differences between patients who died (n=80) and those who survived (n=86) in terms of the ICU length of stay (6 vs. 10 days), septic shock (64 versus 24%), age (51 versus 38 years old), HIV+ condition (34 versus 16%), SOFA (7 versus 4), APACHE (19 versus 13), D-dimer (4.32 versus 2.88 g/ml), PC (46.0 versus 63.5 %) and PAI-1 (33.0 versus 16.5 UA/l). When we used a regression analysis with dichotomized variables, only the SOFA 4 , PAI-1 16 , HIV status and the PAI-1 4G allele proved to be predictors of death at time zero. Conclusions: In the future, ICU scores may be further improved by adding certain genomic or plasma data.

The 4G/4G Genotype of PAI-1 Polymorphism Is Associated with Higher Plasma PAI-1 Concentrations and Mortality in Patients with Severe Sepsis

“…Previous studies have found higher plasma PAI-1 concentrations in septic patients than in controls [25–28], and higher plasma PAI-1 concentrations in non-surviving than in surviving septic patients [3–12]. In addition, patients with the PAI-1 4G/4G genotype had a higher risk of death than patients with the 4G/5G or 5G/5G genotypes, according to a recently published meta-analysis [21].…”

“…Previous studies have found higher plasma PAI-1 concentrations in non-surviving than in surviving septic patients [3–12]. In addition, the association between PAI-1 4G/5G polymorphism and mortality in septic patients has been studied [10–20].…”

“…A recently published meta-analysis [21], including most of those studies [10–19], found that patients with the 4G/4G genotype of the PAI-1 gene had a higher risk of death than patients with 4G/5G or 5G/5G genotypes. However, only 3 of those studies also measured plasma PAI-1 concentrations [10–12]. Two studies have reported that patients with the 4G/4G genotype of the PAI-1 gene had higher plasma PAI-1 concentrations and higher risk of death than those with the 4G/5G or 5G/5G genotypes; one study involved 175 children with meningococcal disease [10], and the other included 88 adult patients with septic shock [11].…”

“…Two studies have reported that patients with the 4G/4G genotype of the PAI-1 gene had higher plasma PAI-1 concentrations and higher risk of death than those with the 4G/5G or 5G/5G genotypes; one study involved 175 children with meningococcal disease [10], and the other included 88 adult patients with septic shock [11]. Another study with 166 adult septic patients reported that patients with the 4G/4G genotype and that patients with higher plasma PAI-1 concentrations had a higher risk of death; however, an association between PAI-1 4G/5G polymorphism and plasma PAI-1 concentrations was not reported [12]. Thus, the objective of this study was to determine whether there is an association between carriage of the PAI-1 4G/4G genotype, plasma PAI-1 concentrations and mortality in a large series of adult septic patients.…”

TIMP-1 gene polymorphism: are genetics able to predict outcome of septic patients?

“…The majority of sepsis studies evaluated other inflammatory mediators, such as TNF and its polymorphisms being associated with increasing stages of sepsis [11,12]. A meta-analysis of two common Toll-like receptor 4 polymorphisms showed no strong correlation with the development of sepsis [13].…”