Systemic activation of coagulation and fibrinolysis in a porcine model of serogroup A streptococcal shock

In a porcine model of Gram-positive sepsis, 28 juvenile pigs were studied t o evaluate the effect of a continuous infusion of live serogroup A streptoc occi (GAS) on the activation of coagulation and fibrinolysis. Plasma levels of thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t- PA) and plasminogen activator inhibitor-1 (PAI-1) activities were measured using commercially available kits. The continuous infusion of GAS [(3-5)x 1 0(8) colony forming units/kg per h] caused early signs of severe septicaemi a in the pigs, with pulmonary hypertension, systemic hypotension, reduced c ardiac output and liver hypoyerfusion, ultimately leading to shock with a h igh mortality. There was a sequential and ordered activation of the coagula tion, fibrinolytic and antifibrinolytic systems. GAS infusion induced a gra dual, maximally 2.5-fold increase in plasma TAT levels. Plasma t-PA activit y levels peaked at 2 h (nine-fold increase), whereas the peak of PAI-1 acti vity was delayed (eight-fold increase at 4 h). These findings are similar t o changes observed during endotoxin infusion. This procoagulant state favou rs disseminated intravascular coagulation and microthrombus formation, ulti mately threatening tissue viability. (C) 2000 Lippincott Williams & Wilkins .