Coagulative Biomarkers Differently Predict Clinical Outcomes in Invasive Infections Caused by Neisseria Meningitidis and Streptococcus Pneumoniae

Abstract

Background: Coagulation plays a crucial role in innate immune response to invasive infections. Coagulative biomarkers might predict clinical outcomes differently, depending on etiology.

Methods: A retrospective study was conducted during a 79-month period, recruiting 90 patients with meningitis or bloodstream infection caused by Neisseria meningitidis (n = 47) or Streptococcus pneumoniae (n = 43), median age 19 and 58 years, respectively. Biomarkers were assessed within 24 hours.

Results: For N. meningitidis: in univariate analysis, increasing D-dimer was associated with in-hospital mortality (odds ratio [OR] 1.360; 95% confidence interval [CI], 1.063-1.889); in multivariate regression, increasing D-dimer was predictive (OR 1.037; 95% CI, 1.001-1.074) of the composite outcome (in-hospital mortality or amputations or hearing loss or neurological sequelae); protein C showed a clear trend toward lower levels in nonsurvivors (26% vs 48%) and in patients with the composite outcome (32% vs 51%); activated partial thromboplastin time (aPTT) was significantly prolonged in nonsurvivors (51.3 vs 35.3 seconds, P = .003), confirmed in univariate analysis (OR 1.122; 95% CI, 1.031-1.253). For S. pneumoniae: antithrombin was significantly lower in nonsurvivors (70% vs 81%, P = .038), confirmed in univariate analysis (OR 0.961; 95% CI, 0.921-0.997). For overall population: in multivariate regression, increasing age was associated with mortality (OR 1.043; 95% CI, 1.010-1.077), and S. pneumoniae etiology with the composite outcome (OR 6.024; 95% CI, 1.798-20.180).

Conclusions: For invasive infections caused by N. meningitidis, D-dimer is a biomarker capable of predicting unfavorable clinical outcomes; a potential role is suggested for aPTT prolongation and protein C decrease, and, in case of S. pneumoniae infections, for antithrombin decrease.

Keywords: Antithrombin; Biomarker; D-dimer; PT; Protein C; Protein S; Sepsis; aPTT.