Summary
Variables of the fibrinolytic system were prospectively studied in patients with haematologic
malignancies in chemotherapy-induced leukocytopenia at onset and during the course
of septicemia to evaluate their prognostic value. This group of patients was chosen
because of their high risk of developing severe septic complications, thus allowing
serial prospective testing of fibrinolytic variables prior to and during evolving
sepsis or septic shock. 62 patients with febrile infectious events were accrued to
the study. Of these, 13 patients progressed to severe sepsis and an additional 13
patients to septic shock as defined according to standard diagnostic criteria. At
onset of fever, plasminogen activator inhibitor (PAI) activity and PAI-1 antigen levels
increased from normal baseline levels and were significantly higher in the group of
patients who developed septic shock compared to those with severe sepsis (medians:
10.6 versus 1.3 U/ml, p = 0.0001; 50.0 versus 5.0 ng/ml, p = 0.0002). The increase
in PAI activity and antigen in septic shock was accompanied by an increase in tissue-type
plasminogen activator antigen and total fibrin(ogen) degradation products and a decrease
in alpha2-antiplasmin activity (p < 0.006). In contrast, in the group of patients
that developed severe sepsis the variables of the fibrinolytic system remained unchanged
at onset of fever. These differences between septic shock apd severe sepsis were sustained
throughout the septic episode for all variables (p <0.0001). PAI activity of >5 U/ml
at onset of fever predicted a lethal outcome with a sensitivity of 92% and a specificity
of 100%. Thus, septic shock in leukocytopenia is associated with significant activation
of the fibrinolytic system presumably as a response of the vascular endothelium to
inflammatory injury. Furthermore, PAI activity measurements are sensitive markers
of an unfavourable prognosis.
