Application of thrombelastography in liver injury induced by endotoxin in rat.
ABSTRACT Liver injury developing in patients with sepsis may lead to an increased risk of mortality. Thrombelastography (TEG) is generally applied to evaluate hemostatic disturbance in patients undergoing liver transplantation or cardiopulmonary bypass. The aim of this study was to investigate the development of liver injury and coagulopathy in a lipopolysaccharide (LPS)-induced animal model and to assess the relationship between TEG variables and liver injury. Male Wistar rats received LPS (30 mg/kg over a 4-h intravenous infusion) to induce experimental liver injury or isotonic saline as a control. Variables of hemodynamics and liver biochemistry were measured during the subsequent 6 h after the start of infusion. TEG variables (R-time, K-time, α-angle and maximal amplitude), thrombin-antithrombin complex and plasminogen activator inhibitor-1 were also measured. After LPS infusion, liver injury [examined by biochemical variables (e.g. alanine aminotransferase, ALT) and histological studies] was developed and inflammatory cytokines (tumor necrosis factor-α and interleukin-6) were raised. At the initial period of LPS infusion, R-time was shortened and α-angle was increased. Thereafter, α-angle and maximal amplitude were decreased progressively, demonstrating that endotoxin induced coagulation disturbances. Furthermore, there were strong positive correlation between K-time and natural log (Ln)(ALT) (r = 0.823, P = 0.001); also, there were strong negative correlations between α-angle and Ln(ALT) (r = -0.762, P = 0.002) as well as maximal amplitude and Ln(ALT) (r = -0.732, P = 0.004) at 6 h after LPS infusion. These results demonstrated that TEG could be a potential tool to evaluate the development of liver injury in endotoxemia.
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ABSTRACT: Sepsis induces early activation of coagulation and fibrinolysis followed by late fibrinolytic shutdown and progressive endothelial damage. The aim of the present study was to investigate and compare the functional hemostatic response in whole blood and plasma during experimental human endotoxemia by the platelet function analyzer, Multiplate and by standard and modified thrombelastography (TEG). Prospective physiologic study of nine healthy male volunteers undergoing endotoxemia by means of a 4-hour infusion of E. coli lipopolysaccharide (LPS, 0.5 ng/kg/hour), with blood sampled at baseline and at 4 h and 6 h. Physiological and standard biochemical data and coagulation tests, TEG (whole blood: TEG, heparinase-TEG, Functional Fibrinogen; plasma: TEG±tissue-type plasminogen activator (tPA)) and Multiplate (TRAPtest, ADPtest, ASPItest, COLtest) were recorded. Mixed models with Tukey post hoc tests and correlations were applied. Endotoxemia induced acute SIRS with increased HR, temperature, WBC, CRP and procalcitonin and decreased blood pressure. It also induced a hemostatic response with platelet consumption and reduced APTT while INR increased (all p<0.05). Platelet aggregation decreased (all tests, p<0.05), whereas TEG whole blood clot firmness increased (G, p = 0.05). Furthermore, during endotoxemia (4 h), whole blood fibrinolysis increased (clot lysis time (CLT), p<0.001) and Functional Fibrinogen clot strength decreased (p = 0.049). After endotoxemia (6 h), whole blood fibrinolysis was reduced (CLT, p<0.05). In contrast to findings in whole blood, the plasma fibrin clot became progressively more resistant towards tPA-induced fibrinolysis at both 4 h and 6 h (p<0.001). Endotoxemia induced a hemostatic response with reduced primary but enhanced secondary hemostasis, enhanced early fibrinolysis and fibrinogen consumption followed by downregulation of fibrinolysis, with a discrepant fibrinolytic response in plasma and whole blood. The finding that blood cells are critically involved in the vasculo-fibrinolytic response to acute inflammation is important given that disturbances in the vascular system contribute significantly to morbidity and mortality in critically ill patients.PLoS ONE 01/2013; 8(3):e59368. · 3.73 Impact Factor