Elevation of plasma free PAI-1 levels as an integrated endothelial response to severe burns

To clarify the role of plasminogen activator inhibitor type 1 (PAI-1) in po stburn hypercoagulation, we assayed the plasma levels of tissue-type plasmi nogen activator (t-PA) antigen, total PAI-1 antigen, and total t-PA-PAI-1 c omplex in 15 burned patients. The total body surface area of the burn injur y ranged from 30 to 80%. Serial blood samples were collected from 12 to 168 h following the thermal injury. The plasma t-PA level and the free PAI-1 l evel increased significantly in the immediate postburn period, and the perc ent increase in the latter over the values in the healthy controls was much greater than that of the former. The ratio of the concentrations of t-PA-P AI-1 complex to free PAI-1 decreased throughout the 7 postburn days. The fa ct that the decreases in this ratio clearly showed no dissociation of the e uglobulin fraction suggests that the postburn hypofibrinolysis occurred as a result of increased synthesis of PAI-1. On the other hand, changes in sev eral parameters of the coagulation or fibrinolysis system and in plasma thr ombomodulin showed that postburn hypercoagulability is associated with seco ndary hyperfibrinolysis with no evidence of vascular endothelial injury. Th e praradoxical coexistence of postburn hyper- and hypofibrinolysis is a goo d reflection of the character of PAI-1, which is a biphasic protein that is both a functional protein and an acute phase reactant. Thus, increased syn thesis of PAI-1 may not enhance postburn hypercoagulability to create a coa gulation-dominant type of disseminated intravascular coagulation severe eno ugh to trigger multiple organ dysfunction syndrome. In conclusion, increase d synthesis of PAM in the initial postburn period reflects an integrated en dothelial response to burn stress, and because it is a functional protein, the concentration of free PAI-1 antigen may be an important index for predi cting secondary consumption coagulopathy. (C) 2001 Elsevier Science Ltd and ISBI. All rights reserved.