Study of acute hemocoagulation changes in a porcine endotoxemic shock model using thrombelastography

Abstract

Disseminated intravascular coagulation and fibrinolysis have been associated with lipopolysaccharide (LPS)-induced endotoxemic sepsis. It has been well established by point-of-care (POC) thrombelastography (TEG) that pigs have a hemocoagulation pathophysiology that resembles humans. We evaluated the use of TEG during the development of coagulation abnormalities in a porcine model of endotoxemia. After approval by the Animal Welfare Committee, pigs were instrumented to record hemodynamic variables. Ten days after surgical instrumentation, LPS (50 μg/kg) was infused intravenously over a period of 45 minutes in conscious animals. Hemodynamic parameters were recorded before and for 6 hours after LPS infusion was completed. Simultaneously, blood samples were analyzed using TEG to measure reaction time (R), clotting time (K), alpha angle (α), maximum amplitude (MA), coagulation index (CI), percent lysis at 30 minutes, and percent lysis at 60 minutes. LPS induced profound hemodynamic changes associated with the induced endotoxemia. Concomitantly, a progressive consumption coagulopathy characterized by significant increases in R and K and decreases in α, MA, and CI developed. The overall hemocoagulation profile of the 3 nonsurviving animals (27%) was significantly different than that of the survivors. Fibrinolysis was not detected during the 6-hour evaluation period. All stages of clot formation were affected as demonstrated by TEG (increased R and K, decreased α and MA). Our results suggest that TEG is a rapid method for assessing coagulation abnormalities in early stages of endotoxemia in pigs. TEG could have significant clinical applications as a rapid POC method in human patients with sepsis.