Dysfunctional Endothelium Drives A Pre-Dic State In Endotoxemia

Uncontrolled pro-coagulant responses in sepsis can lead to disseminated intravascular coagulation (DIC), a complication associated with markedly increased mortality. Abnormalities of coagulation, fibrinolysis, and platelet function can lead to both microvascular thrombosis contributing to multi-organ dysfunction syndrome or hemorrhagic complications. To understand the inciting causes of DIC in sepsis, we first evaluated the time course of platelet function, coagulation parameters and markers of endothelial activation following LPS exposure. These studies demonstrated that endothelial dysfunction preceded derangement of platelet function or coagulation parameters. To evaluate the thrombotic response of the endothelium early in endotoxemia, we injured the microvascular endothelium of cremaster arterioles of mice using a laser 1-3 hours following LPS exposure. Platelet and fibrin formation at sites of injury were significantly increased following LPS exposure to respectively 190% (p=0.026) and 195% (p +/- mice in the absence of LPS. Fibrin generation at sites of laser injury was significantly increased in Tie2 +/- mice to 192% of littermate (Tie2 +/+ ) controls (p Disclosures No relevant conflicts of interest to declare.