TIME-COURSE OF HEMOSTATIC ABNORMALITIES IN SEPSIS AND ITS RELATION TOOUTCOME

Objectives: To investigate the time course and the relation to prognos is of coagulation and fibrinolytic abnormalities in patients with sept ic shock. Patients and Methods: Forty-eight consecutive patients admit ted to the medical ICU with the diagnosis of septic shock (diagnosed b y defined criteria) were studied. Mortality was 25 of 48. Mean age was 57 +/- 7.3 years. Blood samples were obtained on days 1, 4, and 7 aft er hospital admission to measure tissue-type plasminogen activator ant igen (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor antigen (PAI-1), plasminogen, alpha2-antiplasmin, fibrinogen, antithrombin III, protein C, protein S, thrombin-antithrom bin complexes (TAT), D-dimer, and von Willebrand factor-related antige n (vWF:Ag). Results: All patients showed marked abnormalities in both the coagulation and fibrinolytic systems. There were signs of coagulat ion activation and elevation of both activators and inhibitors of fibr inolysis. Nonsurvivors showed lower levels of protein C and antithromb in III and higher concentration of TAT than survivors. While both t-PA and PAI-1 concentrations were high in survivors and nonsurvivors, onl y survivors showed a progressive normalization of both parameters duri ng the study period. Low plasminogen levels and plasminogen/alpha2-ant iplasmin ratio were found in both groups, presenting a trend toward no rmalization only in survivors. The differences reported were not appar ent at the time of hospital admission. Conclusions: Septic shock is ch aracterized by coagulation activation and fibrinolysis activation and inhibition. Nonsurvivors present a particular hemostatic profile chara cterized by a more marked activation of coagulation and a more intense inhibition of fibrinolysis. None of the abnormalities studied was sig nificantly different between survivors and nonsurvivors at the time of hospital admission. In the presence of fibrin formation, nonsurvivors present a maintained imbalance in the fibrinolytic response determine d by higher PAI-1 plasma concentration, probably contributing to their poor outcome.