Tissue factor pathway inhibitor dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia.

摘要: Inhibition of the tissue factor pathway has been shown to attenuate activation coagulation and prevent death in a gram-negative bacteremia primate model sepsis. It suggested that influences inflammatory cascades other than system. The authors sought determine effects 2 different doses recombinant inhibitor (TFPI) on endotoxin-induced coagulant, fibrinolytic, cytokine responses healthy humans. Two groups, each consisting 8 men, were studied double-blind, randomized, placebo-controlled crossover study. Subjects occasions. They received bolus intravenous injection 4 ng/kg endotoxin, which was followed by 6-hour continuous infusion TFPI or placebo. Eight subjects 0.05 mg/kg per hour after 0.0125 (low-dose group), 0.2 (high-dose group). Endotoxin induced coagulation, subsequent inhibition fibrinolysis, release proinflammatory antiinflammatory cytokines. dose-dependent attenuation thrombin generation, as measured plasma F1 + thrombin-antithrombin complexes, with complete blockade high-dose TFPI. Endotoxin-induced changes fibrinolytic system levels not altered either low-dose concluded effectively dose-dependently attenuates humans without influencing response. (Blood. 2000;95:1124-1129)