Summary
We have examined the prognostic value of the levels in the blood of granulocyte elastase-α1-proteinase inhibitor (E-α1-PI) complex, tumor necrosis factor-α (TNF-α) and urokinase-type plasminogen activator
(u-PA) in 35 patients with severe infection upon admission to an Intensive Care Unit.
Fourteen patients died.
No differences for E-α1-PI complex were found between survivors and nonsurvivors, but in all patients the
levels on admission were eight-fold higher than the reference value.
TNF-α levels, measured by immunoassay, on admission were four times higher in the
nonsurvivors than in the survivors (p = 0.0003) and correlated with the severity of the disease (APACHE II score, r = 0.43, p <0.05). TNF-α was not detectable by bioassay.
Total u-PA antigen (u-PA Ag), plasmin-activatable single-chain u-PA (scu-PA) and inactive,
nonactivatable u-PA (u-PA#) were on admission all two-fold higher in the nonsurvivors
(p = 0.0006, 0.003 and 0.0003, respectively), while normal in the survivors. In both,
survivors and nonsurvivors, the ratio between scu-PA and u-PA Ag was significantly
decreased (p <0.001, compared to a reference group of healthy volunteers), indicative for enhanced
conversion of scu-PA to active two-chain u-PA (tcu-PA) and inactive u-PA# during severe
infectious disease. tcu-PA was detected in nine of the 35 patients, while virtually
undetectable in controls. scu-PA correlated with the Child-Pugh score on admission
(r = 0.42, p <0.05). TNF-α correlated with u-PA Ag (r = 0.38, p <0.05) and with u-PA# (r = 0.47, p <0.01).
In a stepwise logistic regression analysis, documentation of infection and plasma
levels of u-PA Ag contributed most significantly to prediction of patient outcome.
Serum levels of TNF-α did not. These results suggest that, in addition to a number
of other clinical and laboratory parameters, u-PA Ag can be used as a prognostic marker
in patients with severe infection admitted to an Intensive Care Unit.