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Fibrinolytic changes in a patient with toxic shock syndrome; release of active u-PA
1Department of Medicine & Therapeutics, University of Aberdeen Medical School, Foresterhill UK.
Objective:
Definition of the changes in the activators of plasminogen, u-PA and t-PA, and examination of the possible generation of plasmin in the circulation in overwhelming sepsis.
Design:
Serial blood analysis starting 4 h after development of symptoms of toxic shock syndrome.
Setting:
Intensive care unit.
Patient:
A previously healthy woman underwent endometrial ablation and rapidly thereafter developed staphylococcal toxic shock syndrome with organ failure. MEASUREMENT AND RESULT: t-PA, PAI-1, t-PA-PAI-1 complexes, plasminogen, fibrinogen and plasmin-alpha 2-antiplasmin complexes were measured serially by ELISA and free u-PA by SDS-PAGE with zymography. The onset of symptoms was accompanied by a rise of t-PA antigen-followed rapidly by PAI-1 antigen. Plasmin-alpha 2-antiplasmin complex was generated in large amounts but disappeared within hours. From day 3, free u-PA was detectable in the circulation without plasmin generation.
Conclusion:
Despite the sustained presence of active u-PA in the circulation and of t-PA antigen at the onset of symptoms, plasmin-alpha 2-antiplasmin generation was largely suppressed by high levels of PAI-1. The suppression of plasmin generation by u-PA and t-PA may ensure the persistence of fibrin in the microcirculation and so contribute to organ failure.