Early persisting elevation of plasma Pentraxin 3 is associated with mortality and with coagulation impairment in severe sepsis and septic shock

Introduction

Pentraxin 3 (PTX3) is an inflammatory mediator produced by a variety of tissue cells, like neutrophils, macrophages, myeloid dendritic, endothelial and epithelial cells [1]. During sepsis a massive inflammatory activation occurs, which often leads to an important coagulation system dysfunction. PTX3 upregulates coagulation promoters in vitro [2]. PTX3 may represent an early marker of severity and outcome and may be related to coagulation impairment in septic patients.

Methods

We studied 90 patients affected by severe sepsis or septic shock previously enrolled in a prospective trial regarding the impact of glycemic control on inflammation and coagulation. At enrollment we recorded sepsis signs, plasminogen activator inhibitor 1 (PAI-1, an inhibitor of fibrinolysis) activity and concentration, prothrombin fragments 1 + 2 (F1+2) concentration (a marker of coagulation activation), disease severity and organ dysfunctions. We measured plasma PTX3 levels at enrollment and everyday until day 7. Mortality was recorded at day 90.

Results

Although not different on day 1, PTX3 remained significantly higher in nonsurvivors than in survivors over the first 5 days (P = 0.002 by general linear model). On day 1, septic shock patients had higher PTX3 levels than patients with severe sepsis (274.41 ± 321.92 vs 114.95 ± 129.93 ng/ml, P = 0.029, t test). Day 1 PTX3 was significantly correlated with SAPS II score (R² = 0.08, P = 0.006, linear regression), platelets count (R² = 0.14, P < 0.001) and SOFA score (R² = 0.16, P < 0.001). Day 1 PTX3 was correlated with PAI-1 concentration (R² = 0.211, P < 0.001) and activity (R² = 0.231, P < 0.001) and with F1+2 concentration (R² = 0.09, P = 0.045).

Conclusions

Persisting high levels of circulating PTX3 over the first days from sepsis onset may be associated with mortality. PTX3 correlates with severity of sepsis and with sepsis-associated coagulation dysfunction.