Plasminogen activator inhibitor 2 and urokinase-type plasminogen activatorin plasma and leucocytes in patients with severe sepsis

Proteins influencing plasminogen activation to plasmin, namely plasminogen activators tissue-type plasminogen activator (t-PA) and urokinase-type plas minogen activator (u-PA) and their principal inhibitors, plasminogen activa tor inhibitor 1 (PAI-1) and PAI-2, were measured in the plasma, the polymor ph and mononuclear cell fractions taken from patients with major sepsis who were entering a general intensive care unit, The purpose of this study was to elucidate the factors favouring the persistence of fibrin in the microv asculature and thus contributing to multiple organ failure. Levels of u-PA antigen in plasma rose in sepsis and u-PA activity not detectable in normal plasma, appeared. Levels of u-PA antigen in the cell fractions fell concom itantly. t-PA antigen in plasma and in the mononuclear cell fraction rose i n sepsis, but t-PA activity was not detectable. Plasma PAI-1 antigen levels were strikingly raised in sepsis, presumably accounting for the complete n eutralization of t-PA activity. PAI-2 antigen, not normally detected in pla sma, appeared in the plasma of some patients, whereas it disappeared from t he cellular fractions. Appearance of PAI-2 in plasma was associated with no n-survival of the patient, The observations indicate that all the agents in volved in plasminogen activation are released into the plasma in major seps is. The levels of PAI-1 reached were quantitatively sufficient to suppress all activity of the released t-PA, but the inhibitors did not prevent expre ssion of u-PA activity in the circulation, Circulating active u-PA and PAI- 2 in the plasma of patients with severe sepsis may represent material origi nating from leucocytes. Leucocyte release of these agents within fibrin dep osits may influence the persistence of fibrin and thus the development of m ultiple organ failure.