Endotoxinemia-induced changes in coagulation as measured by rotation thrombelastometry technique and conventional laboratory tests: results of a pilot study on pigs

Abstract

Modified rotation thrombelastometry (ROTEM) is widely used in near-patient assessment of hemostasis, but data on functional consequences initiated by acute endotoxinemia are rare. To test the hypothesis that the ROTEM technique allows detection of endotoxinemia-induced changes in hemostasis, we conducted a pilot study on pigs. Fifteen healthy pigs were anesthetized and instrumented for invasive hemodynamic monitoring. Several coagulation tests and the ROTEM assay were performed at baseline and 60 min after administration of a bolus of 200 mg of Escherichia coli lipopolysaccharide followed by a continuous infusion of 0.1 mg/kg per min. After induction of acute endotoxinemia, clot formation time increased (P U 0.001), and a angle (P U 0.001) and maximum clot firmness decreased significantly (P U 0.001) in intrinsically and extrinsically activated ROTEM assays. Moreover, fibrinogen/fibrin polymerization showed significantly lower values during endotoxinemia (P U 0.001), and coagulation time shortened for the intrinsically activated assay (P U 0.017). Simultaneously, a significant decrease in platelet count (P U 0.001), fibrinogen (P U 0.001), antithrombin and protein C (P U 0.001) was registered, whereas results of standard coagulation tests and D-dimers showed no significant changes although thrombinantithrombin complex increased (P U 0.001).Wilcoxon Z score analysis showed that changes in ROTEM variables were comparable to changes in antithrombin, protein C, platelet count, white blood cells and fibrinogen concentrations. The ROTEM assays were able to reflect endotoxinemia-dependent changes in the hemostatic system in pigs early by showing not only activation but also signs of consumption, whereas results of routine coagulation tests remained unchanged. Blood Coagul

Discrepant Fibrinolytic Response in Plasma and Whole Blood during Experimental Endotoxemia in Healthy Volunteers

“…This has been documented by TEG/ROTEM and has been reproduced in studies using experimental human [23] and animal [25]–[27] models of endotoxemia [23], [25]–[27]. Also, platelet aggregation is profoundly reduced in septic patients [19]–[22] and decreases with disease severity [20]–[22], which has also been reproduced in experimental human [23], [24] and animal [28], [29] models of endotoxemia.…”

“…Multiple Platelet function Analyzer; Multiplate®, Verum Diagnostica GmbH, Munich, Germany) [8] reveal both fibrinolysis and platelet function. Several studies have characterized the coagulopathy in sepsis [9]–[22] and experimental human [23], [24] and animal [25]–[29] endotoxemia by these tests.…”

Changes in fibrinolysis and severity of organ failure in sepsis: A prospective observational study using point-of-care test—ROTEM

“…In sepsis, increased endothelial synthesis of plasminogen activator inhibitor-1 (PAI-1) has been shown to be the main inhibitor of fibrinolysis [4,5]. The balance between clot formation and fibrinolysis has been difficult to investigate; the readily available conventional coagulation tests may be misleading [8,9], and fibrinolysis has been difficult to accurately quantify despite measuring the fibrin degradation product-D-dimer.…”

“…The principle advantage of thromboelastometry is its ability to quickly reflect the end-result of complex interactions between all components of the hemostatic system (including cells). Thromboelastometry has already been shown to be a highly sensitive assay capable of detecting distinct, and very early as well as late changes in coagulation in endotoxemia and severe sepsis [8,9]. It also provides information about fibrinolysis using parameters such as "maximum lysis" (ML) [11][12][13].…”

Comparison of thrombelastometry with procalcitonin, interleukin 6, and C-reactive protein as diagnostic tests for severe sepsis in critical ill adults

“…In a recent study, we demonstrated that endotoxinemia can be detected with thromboelastometry under in vitro conditions [5]. Thromboelastometric variables remained within reference ranges during the course of critically illness in 30 patients with sepsis [6]. In another study, however, early changes in thromboelastometry values were demonstrated in endotoxin-treated pigs [7].…”