Objective:Definition of the changes in the activators of plasminogen,
u-PA and t-PA, and examination of the possible generation of plasmin i
n the circulation in over-whelming sepsis. Design: Serial blood analys
is starting 4 h after development of symptoms of toxic shock syndrome.
Setting: Intensive care unit. Patient: A previously healthy woman und
erwent endometrial ablation and rapidly thereafter developed staphyloc
occal toxic shock syndrome with organ failure. Measurement and result:
t-PA, PAI-1, t-PA-PAI-1. complexes, plasminogen, fibrinogen and plasm
in-alpha(2)-antiplasmin complexes were measured serially by ELISA and
free u-PA by SDS-PAGE with zymography The onset of symptoms was accomp
anied by a rise of t-PA antigen followed rapidly by PAI-1 antigen. Pla
smin-alpha(2)-antiplasmin complex was generated in large amounts but d
isappeared within hours. From day 3, free u-PA was detectable in the c
irculation without plasmin generation. Conclusion: Despite the sustain
ed presence of active u-PA in the circulation and of t-PA antigen at t
he onset of symptoms, plasmin-alpha(2)-antiplasmin generation was larg
ely suppressed by high levels of PAI-1. The suppression of plasmin gen
eration by u-PA and t-PA may ensure the persistence of fibrin in the m
icrocirculation and so contribute to organ failure.