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Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection; no current clinical measure adequately reflects the concept of dysregulated response. Coagulation plays a pivotal role in the normal response to pathogens (immunothrombosis), thus the evolution toward sepsis-induced coagulopathy could be individuate through coagulation/fibrinolysis-related biomarkers. We focused on the role of D-dimer assessed within 24 h after admission in predicting clinical outcomes in a cohort of 270 patients hospitalized in a 79 months period for meningitis and/or bloodstream infections due to  Streptococcus pneumoniae  ( n  = 162) or  Neisseria meningitidis  ( n  = 108). Comparisons were performed with unpaired  t -test, Mann-Whitney-test or chi-squared-test with continuity correction, as appropriate, and multivariable logistic regression analysis was performed with Bayesian model averaging. In-hospital mortality was 14.8% for the overall population, significantly higher in  S. pneumoniae  than in  N. meningitidis  patients: 19.1 vs. 8.3%, respectively ( p  = 0.014). At univariable logistic regression analysis the following variables were significantly associated with in-hospital mortality: pneumococcal etiology, female sex, age, ICU admission, SOFA score, septic shock, MODS, and D-dimer levels. At multivariable analysis D-dimer showed an effect only in  N. meningitidis  subgroup: as 500 ng/mL of D-dimer increased, the probability of unfavorable outcome increased on average by 4%. Median D-dimer was significantly higher in  N. meningitidis  than in  S. pneumoniae  patients (1,314 vs. 1,055 ng/mL,  p  = 0.009). For  N. meningitidis  in-hospital mortality was 0% for D-dimer <500 ng/mL, very low (3.5%) for D-dimer <7,000 ng/mL, and increased to 26.1% for D-dimer >7,000 ng/mL. Kaplan-Meier analysis of in-hospital mortality showed for  N. meningitidis  infections a statistically significant difference for D-dimer >7,000 ng/mL compared to values <500 ng/mL ( p  = 0.021) and 500–3,000 ng/mL ( p  = 0.002). For  S. pneumoniae  the mortality risk resulted always high, over 10%, irrespective by D-dimer values. In conclusion, D-dimer is rapid to be obtained, at low cost and available everywhere, and can help stratify the risk of in-hospital mortality and complications in patients with invasive infections due to  N. meningitidis : D-dimer <500 ng/mL excludes any further complications, and a cut-off of 7,000 ng/mL seems able to predict a significantly increased mortality risk from much <10% to over 25%.

frontiers in medicine

D-Dimer as Biomarker for Early Prediction of Clinical Outcomes in Patients With Severe Invasive Infections Due to Streptococcus Pneumoniae and Neisseria Meningitidis