INCREASE OF PLASMINOGEN-ACTIVATOR INHIBITOR LEVELS PREDICTS OUTCOME OF LEUKOCYTOPENIC PATIENTS WITH SEPSIS

Variables of the fibrinolytic system were prospectively studied in pat ients with haematologic malignancies in chemotherapy-induced leukocyto penia at onset and during the course of septicemia to evaluate their p rognostic value. This group of patients was chosen because of their hi gh risk of developing severe septic complications, thus allowing seria l prospective testing of fibrinolytic variables prior to and during ev olving sepsis or septic shock. 62 patients with febrile infectious eve nts were accrued to the study. Of these, 13 patients progressed to sev ere sepsis and an additional 13 patients to septic shock as defined ac cording to standard diagnostic criteria. At onset of fever, plasminoge n activator inhibitor (PAI) activity and PAI-1 antigen levels increase d from normal baseline levels and were significantly higher in the gro up of patients who developed septic shock compared to those with sever e sepsis (medians: 10.6 versus 1.3 U/ml, p = 0.0001; 50.0 versus 5.0 n g/ml, p = 0.0002). The increase in PAI activity and antigen in septic shock was accompanied by an increase in tissue-type plasminogen activa tor antigen and total fibrin(ogen) degradation products and a decrease in alpha(2)-antiplasmin activity (p < 0.006). In contrast, in the gro up of patients that developed severe sepsis the variables of the fibri nolytic system remained unchanged at onset of fever. These differences between septic shock and severe sepsis were sustained throughout the septic episode for all variables (p < 0.0001). PAI activity of > 5 U/m l at onset of fever predicted a lethal outcome with a sensitivity of 9 2% and a specificity of 100%. Thus, septic shock in leukocytopenia is associated with significant activation of the fibrinolytic system pres umably as a response of the vascular endothelium to inflammatory injur y. Furthermore, PAI activity measurements are sensitive markers of an unfavourable prognosis.