Edoxaban, a direct oral factor Xa inhibitor, ameliorates coagulation, microvascular thrombus formation, and acute liver injury in a lipopolysaccharide-induced coagulopathy model in rats

AbstractInfection increases the risk of thrombosis through the activation of inflammation and coagulation. Edoxaban, a direct oral factor Xa inhibitor, is used for the prevention and treatment of thrombotic diseases. The aim of this study was to determine the effects of edoxaban on microvascular thrombus formation in a rat model of lipopolysaccharide (LPS)-induced coagulopathy. Rats were intravenously injected with 7.5  mg/kg of LPS (Escherichia coli 055:B5). Immediately after LPS injection, the rats were treated with subcutaneous injection of edoxaban. At 2 and 6  h after the injection of LPS, biomarkers of coagulation and organ damages and inflammatory cytokines were measured. Microvascular thrombus formation in organs was evaluated using125I-fibrinogen (human) or by the pathological analysis. Mortality was examined 24  h after LPS injection. After the injection of LPS, D-dimer and thrombin-antithrombin complex increased and platelet numbers decreased, indicating the activation of coagulation. Microvascular thrombi were found in the liver. Markers of liver injury (aspartate aminotransferase and alanine aminotrans ferase) also increased. Treatment with edoxaban attenuated the changes in the coagulation markers and microvascular thrombus formation in the liver. Edoxaban suppressed the increase in the liver injury markers and reduced the mortality. Edoxaban did not affect the levels of inflammatory cytokines. I n conclusions, edoxaban significantly inhibited the activation ...
Source: Journal of Thrombosis and Thrombolysis - Category: Hematology Source Type: research