Time course and prognostic significance of hemostatic changes in sepsis: Relation to tumor necrosis factor-alpha

Objectives: To describe the time course and prognostic significance of tumo r necrosis factor-alpha (TNF-alpha) levels and hemostatic abnormalities in clinical sepsis. Design:Prospective, observational study with sequential measurements in an inception cohort. Setting: An emergency department in a university teaching hospital. Patient s were followed up until they either left the hospital or died. Patients: During al-yr period, 43 adult patients were selected from all eme rgency department patients who met the established criteria for sepsis. Exc luded were patients with either organ dysfunction or septic shock at the ti me of admission. Interventions: None. Measurements and Main Results:Blood samples were collected serially (day of admission and on days 3, 5, and 7) to determine TNF-alpha, platelet count, fibrinogen, factor VII, antithrombin ill, tissue-type plasminogen activato r activity, plasminogen activator inhibitor activity, plasminogen, and alph a 2-antiplasmin. Fibrinopeptide A was measured only on the day of admission . Data were analyzed to determine whether admission values or serially obta ined values within 7 days were useful in predicting outcome. Thirteen patie nts died and 30 survived. On admission, assay values indicated that platele t count and antithrombin III were significantly lower than normal (as obser ved in 50 healthy adults). Fibrinogen, plasminogen activator inhibitor type 1, tissue-type plasminogen activator, fibrinopeptide A, and TNF-alpha were higher than normal, whereas concentrations of factor VII, plasminogen, and alpha 2-antiplasmin were in the normal range. No differences were detected in the admission values between survivors and nonsurvivors, except for ant ithrombin ill. However, subsequent values of some variables demonstrated a difference between survivors and nonsurvivors. survivors showed increasing platelet count and antithrombin III values compared with nonsurvivors, in w hom the values remained low, with no significant changes during the study p eriod. High TNF-alpha levels were found in both groups, but only survivors experienced progressive decrease during the observation period. Conclusions:Early clinical sepsis is characterized by high plasma levels of TNF-alpha and by activation of the coagulation and fibrinolysis systems. L ongitudinal analysis of some variables (antithrombin III, platelet count, a nd TNF-alpha) showed some differences with time between the survivor and no nsurvivor groups, but we feel that such differences were not large enough t o be predictive in individual patients.