Table 2.

Sepsis biomarkers, except for C-reactive protein (CRP) and procalcitonin (PCT), that have been evaluated for their prognostic value in clinical studies with more than 300 subjects

Biomarker [ref]	No. of patients	Sepsis definition	Study population	Main finding	Sensitivity/specificity (%)	AUC
Urokinase plasminogen activator receptor (uPAR) [19]	1914	International Sepsis Definitions Conference 2001	Critically ill patients and patients hospitalized in internal medicine ward	Levels ≥ 12 ng/mL predicted fatal outcome within 30 days	NR/> 70%	0.708 0.83 (when combined with APACHE II score)
Plasminogen activator inhibitor (PAI) 1 [20]	1790	ACCP 1992	Septic patients with disseminated intravascular coagulation (DIC)	Levels > 90 ng/mL predict fatal outcome within 30 days	NR (Kaplan-Meier survival functions)	NR
Interleukin (IL)-12 [21]	1444	Proven peritonitis or mediastinitis and systemic inflammation signs	Surgical patients	Pre-surgery IL-12-synthesizing capability was low in patients who had fatal sepsis after operation	NR	0.72
Thrombomodulin [22]	1103	ACCP 1992	Critically ill patients with sepsis	Levels > 14 ng/mL can predict circulatory failure or death—gray zone between 7 and 14 ng/mL	NR (logistic regression analysis)	NR
Syndecan-1 [22]	1103	ACCP 1992	Critically ill patients with sepsis	Levels > 240 ng/mL can predict circulatory failure or death—gray zone between 70 and 240 ng/mL	NR (logistic regression analysis)	NR
Fibrinogen [23]	1103	ACCP 1992	Critically ill patients with sepsis	Levels < 200 mg/dL related to increased risk of fatal outcome	NR (logistic regression analysis)	NR
Antithrombin activity [23]	1103	ACCP 1992	Critically ill patients with sepsis	Decrease in activity > 50% related to increased risk of fatal outcome	NR (logistic regression analysis)	NR
Brain natriuretic peptide (BNP) [24]	1000	International Sepsis Definition Conference 2001	ED patients	Levels > 113 pg/mL can predict fatal outcome within 28 days	86/55	0.73
Angiopoietin-2 [25]	931	NR	Critically ill patients with ARDS	Persistently increased levels related to fatal outcome within 90 days	NR (logistic regression analysis)	NR
Prothrombin time (PT) [26]	840	Suspected infection plus ≥ 3 signs of systematic inflammatory response	Critically ill patients with sepsis	Increase in PT time within first 7 days of sepsis was higher in patients who died within 28 days	NR (no test)	NR
Adrenomedullin [27]	837	International Sepsis Definitions Conference 2001	ED patients sepsis	Levels < 34.4 ng/L predicted fatal outcome within 30 days	86/61	0.77 0.81 (when combined with Mortality in Emergency Department Sepsis (MEDS) score)
Pro-adrenomedullin [28]	896	Clinical suspicion of infection	ED patients with sepsis	Levels ≥ 1.6 nmol/L predicted fatal outcome within 28 days	75/92	0.89
Heparin-binding protein [29]	759	Suspected infection and at least one clinical sign of systematic inflammatory response	ED patients with sepsis	Levels > 30 ng/mL predicted any organ dysfunction development within 72 h	78/76 (cross-tabulation analysis)	NR
D-dimer [30]	684	International Sepsis Definitions Conference 2001	Emergency department patients with sepsis	Higher in non-survivors than survivors within 28 days	NR	0.68
Troponin [31]	598	ACCP 1992	Critically ill patients	Levels > 0.06 ng/mL independent prognostic marker for 28-day mortality	NR (logistic regression analysis)	NR
YKL-40 [32]	502	ACCP 1992	Critically ill patients	Levels ≤ 505 ng/mL predicted survival in 90 days	53/76	0.64
CD64 [13]	468	International Sepsis Definition Conference 2001	Critically ill patients	Sustained elevated levels were related to non-appropriate antibiotic therapy	93/48	0.74
Cell-free DNA [33]	481	International Sepsis Definitions Conference 2001	ED patients	Levels > 1.6 μg/mL predicted short-term fatal outcome	70/76	0.77

ARDS acute respiratory distress syndrome, NR not reported, IL interleukin, SOFA sequential organ failure assessment, AUC area under the receiver operating characteristic curve