Prognostic value of protein C concentrations in neutropenic patients at high risk of severe septic complications

Abstract

Objective To assess the prognostic value of protein C, endogenous activated protein C, and d-dimer concentrations in patients at high risk of developing severe septic complications secondary to cytostatic chemotherapy. Design Prospective, comparative, single-center study. Setting Specialized ward for treating patients with acute leukemia and associated intensive care unit at a university hospital. Subjects Twenty-six consecutive patients who developed either severe sepsis (n = 13) or septic shock (n = 13) during chemotherapy-induced neutropenia (leukocytes 38.3°C). Thirteen patients progressed to severe sepsis and 13 patients to septic shock. Protein C, endogenous activated protein C, and d-dimer were measured in these 26 patients. At fever onset, protein C concentrations decreased from normal baseline concentrations and were significantly lower in the group of patients who progressed to septic shock compared with those who developed severe sepsis (medians for protein C activity: 23.1% vs. 69.5%;p = .0003). The median elapsed time between detection of fever and the diagnosis of severe sepsis or septic shock was 16 hrs and 12 hrs, respectively. All septic shock patients died, whereas patients who progressed only to severe sepsis survived. Conclusions Septic shock in neutropenic patients is associated with increased protein C consumption. The data demonstrate that the coagulation cascade is activated and produces a hypercoagulable state before the onset of clinical symptoms of severe sepsis and septic shock. Low protein C concentrations at the onset of fever and before the onset of clinical symptoms of severe sepsis or septic shock may have prognostic value in predicting an unfavorable outcome. Protein C measurements may help identify patients at risk in an early phase of neutropenic sepsis. It is also attractive to speculate that because low protein C concentrations were seen in these patients, protein C replacement may be beneficial in sepsis.