The evolution of activated protein C plasma levels in septic shock and its association with mortality: A prospective observational study.

PURPOSE: Septic shock is commonly associated with hemostatic abnormalities. The endothelium-activated serine protease activated protein C (APC) plays a pivotal role in limiting coagulation and possesses anti-apoptotic and anti-inflammatory properties. We hypothesized that APC levels correlate with established coagulation parameters and provide prognostic information in patients with septic shock.

METHODS: We conducted a prospective, observational cohort study in patients with septic shock. APC was measured on admission (day 0) and on days 1, 3, and 6 by a clinically applicable oligonucleotide (aptamer)-based enzyme-capture assay (OECA). The primary endpoint was defined as sepsis-associated 30-day mortality. Furthermore, we analyzed the correlation of APC levels with established coagulation markers.

RESULTS: 48 consecutive patients admitted with septic shock were included (mortality 39.6%). APC levels were elevated upon admission (0.59 ng/ml, IQR 0.26-0.97) and showed a strong correlation with established markers of coagulation and lactate. Multivariable logistic regression identified APC (OR 4.3, 95% CI 1.1-17.8, p = 0.04) and lactate levels (OR 7.0, 95% CI 4.1-18.2, p = 0.04) as independent predictors of 30-day mortality.

CONCLUSIONS: APC levels are increased in patients with septic shock and are correlated with established markers of coagulation. Elevated APC levels on admission are an independent predictor of mortality.