当前位置： SCI文献检索 > BLOOD期刊下所有文献 > Tissue factor pathway inhibitor dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia.

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

Abstract：

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

journal_name

Blood

journal_title

Blood

authors

de Jonge E,Dekkers PE,Creasey AA,Hack CE,Paulson SK,Karim A,Kesecioglu J,Levi M,van Deventer SJ,van Der Poll T

subject

Has Abstract

pub_date

2000-02-15 00:00:00

pages

1124-9

issue

eissn

0006-4971

issn

1528-0020

journal_volume

pub_type

临床试验,杂志文章,随机对照试验

在线工具

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