Heparin blunts endotoxin-induced coagulation activation

Article

关键词: DISSEMINATED INTRAVASCULAR COAGULATION;    MOLECULAR-WEIGHT HEPARIN;    FACTOR PATHWAY INHIBITOR;    COLI SEPTIC SHOCK;    TISSUE FACTOR;    SOLUBLE FIBRIN;    UNFRACTIONATED HEPARIN;    INTRAVENOUS ENDOTOXIN;    MONOCLONAL-ANTIBODY;    FACTOR VIIA;   

DOI  :  10.1161/01.CIR.100.25.2485

来源: SCIE

【 摘 要 】

Background-Lipopolysaccharide (LPS) is a major trigger of sepsis-induced disseminated intravascular coagulation (DIC) via the tissue factor (TF)/factor VIIa-dependent pathway of coagulation. Experimental endotoxemia has been used repeatedly to explore this complex pathophysiology, but little is known about the effects of clinically used anticoagulants in this setting. Therefore, we compared with placebo the effects of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) on LPS-induced coagulation. Methods ann Results-In a randomized, double-blind, placebo-controlled trial, 30 healthy male volunteers received LPS 2 ng/kg IV followed by a bolus-primed continuous infusion of UFH, LMWH, or placebo. In the placebo group, activation of coagulation caused marked increases in plasma levels of prothrombin fragment F1+2 (P<0.01) and polymerized soluble fibrin, termed thrombus precursor protein (TpP; P<0.01); TF-positive monocytes doubted in response to LPS, whereas levels of activated factor VII slightly decreased and levels of TF pathway inhibitor remained unchanged. UFH and LMWH markedly decreased activation of coagulation caused by LPS, as F1+2 and TpP levels only slightly increased; TF expression on monocytes was also markedly reduced by UFH. TF pathway inhibitor values increased after either heparin infusion (P<0.01). Concomitantly. factor VIIa levels dropped by >50% at 50 minutes after initiation of either heparin infusion (P<0.01). Conclusions-This experimental model proved the anticoagulatory potency of UFH and LMWH in the initial phase of experimental LPS-induced coagulation. Successful inhibition of thrombin generation also translates into blunted activation of coagulation factors upstream and downstream of thrombin.

【 授权许可】

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