Heparin blunts endotoxin-induced coagulation activation

Background-Lipopolysaccharide (LPS) is a major trigger of sepsis-induced di sseminated intravascular coagulation (DIC) via the tissue factor (TF)/facto r VIIa-dependent pathway of coagulation. Experimental endotoxemia has been used repeatedly to explore this complex pathophysiology, but little is know n about the effects of clinically used anticoagulants in this setting. Ther efore, 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-pr imed continuous infusion of UFH, LMWH, or placebo. In the placebo group, ac tivation of coagulation caused marked increases in plasma levels of prothro mbin 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 leve ls of TF pathway inhibitor remained unchanged. UFH and LMWH markedly decrea sed activation of coagulation caused by LPS, as F1+2 and TpP levels only sl ightly increased; TF expression on monocytes was also markedly reduced by U FH. TF pathway inhibitor values increased after either heparin infusion (P< 0.01). Concomitantly. factor VIIa levels dropped by >50% at 50 minutes afte r initiation of either heparin infusion (P<0.01). Conclusions-This experimental model proved the anticoagulatory potency of U FH and LMWH in the initial phase of experimental LPS-induced coagulation. S uccessful inhibition of thrombin generation also translates into blunted ac tivation of coagulation factors upstream and downstream of thrombin.