Severe protein C deficiency is associated with organ dysfunction in patients with severe sepsis

Abstract

Purpose The aim of this study was to assess the relationship between protein C levels and temporal changes in organ dysfunction. Materials and Methods Using data from the placebo arm of Recombinant Human Activated PROtein C Worldwide Evaluation in Severe Sepsis trial (N = 775), we compared the development of organ dysfunction over time, in adult severe sepsis patients with and without severe protein C deficiency. Results At study enrollment (baseline), patients with and without severe protein C deficiency were similar in age and likelihood of comorbidities. Patients with severe protein C deficiency had lower arterial blood pressure ( P = .0006), greater serum creatinine concentration ( P < .0001), elevated markers of thrombosis and inflammation, and impairment of fibrinolysis ( P < .0001). The baseline PaO 2/FiO 2 ratio was not significantly different between the 2 groups. Seven days after study enrollment, cardiovascular and renal function remained significantly worse in patients with severe protein C deficiency ( P < .0001), and respiratory dysfunction was greater ( P < .0001). Baseline protein C deficiency was seen to be associated with subsequent pulmonary, renal, and hematologic organ failure. Conclusions Severe protein C deficiency in patients with severe sepsis is associated with both the incidence and severity of organ dysfunction and subsequent worsening of organ function and may be a useful predictor of organ failure in severe sepsis.