Activation of the extrinsic coagulation pathway in patients with severe sepsis and septic shock

Objectives: To obtain systematic information on the extrinsic coagulation p athway, as well as to investigate the time course of the coagulation abnorm alities in sepsis. Design: Prospective observational study. Setting: General intensive care unit. Patients: Nineteen patients with the diagnosis of severe sepsis or septic s hock and nine control patients. Interventions: None. Measurements and Main Results: Tissue factor antigen concentration (tissue factor antigen), prothrombin fragment F1+2, thrombin antithrombin III compl ex, fibrinopeptide A, D-dimer, and antithrombin III concentrations were mea sured on the day of diagnosis of severe sepsis and septic shock, and on day s 1, 2, 3, and 4 after diagnosis. The concentrations of tissue factor antig en, prothrombin fragment F1+2, fibrinopeptide A, and D-dimer were significa ntly increased in patients with severe sepsis and septic shock compared wit h control subjects. However, the concentrations of thrombin antithrombin II I complex showed no statistical differences between the septic patients and the control subjects. Significantly, low antithrombin III concentrations w ere observed in the septic patient groups compared with control subjects. W ith the exception of D-dimer, the concentrations of the hemostatic markers were similar between severe sepsis and septic shock patients. Significant c orrelations were noted between tissue factor antigen and the disseminated i ntravascular coagulation score (r(2) = .236, p < .0001) and the number of d ysfunctioning organs (r(2) = .229, p = .035). Conclusions: We systematically elucidated coagulation disorders in newly de fined sepsis. The extrinsic coagulation pathway is activated in patients wi th severe sepsis and septic shock. In these patients, enhanced thrombin gen eration and activation, and fibrin formation were demonstrated when compare d with the control subjects. Furthermore, the thrombin generated appears no t to be fully neutralized by antithrombin III.