Matt Harmon

126 Chapter six cooling was initiated. There was no difference in EXTEM CA5 – FIBTEM CA5 (a measure of platelet function) between the fever group and the normothermia group (Figure 3F, p = 0.38) despite differences in platelet levels between groups. G-values, which may indicate a hypercoagulable state, were not different between groups (p = 0.15). Discussion In this study, we investigated the effect of induced normothermia on coagulation status during LPS-induced endotoxemia in healthy volunteers. The main finding of this study is that induced normothermia reversed LPS induced thrombocytopenia and DIC scores compared patients with fever. Also, elevated vWf antigen levels were decreased. Thereby, normothermia reverses coagulation derangements as seen during sepsis-induced coagulopathy. LPS-induced endotoxemia in human volunteers resulted in derangements of the coagulation system resembling those noted in sepsis-induced consumption coagulopathy and DIC. The observed coagulation abnormalities induced by LPS are concurrent with previous studies on sepsis induced coagulopathy, including activation of the endothelium and increased secretion of vWf, resulting in activation of platelets. 13 These platelets have a high capacity to aggregate, causing clumping of platelets with an ensuing decrease in circulating platelets. 14, 15 LPS also prolonged PT, presumably due to activation and consumption of coagulation factors in the formation of microthrombi. Together, LPS induces an increase in DIC scores. 16 The decrease in aPTT following LPS is most likely caused by coagulation factor VIII as LPS is known to increase factor VIII. 17 Cooling to normothermia prevented several LPS-induced derangements. Induced normothermia maintained platelet levels compared to the fever group. Overall, prolongation of PT and increase in D-dimer levels were less outspoken in the normothermia group compared to the fever group. This resulted in decreased DIC scores in the normothermia group, as well as in a reduction of the number of volunteers with severe DIC scores. Of note, fibrinogen levels were unaffected by cooling. Possibly, an absence of effect is due to the chosen timeframe. In LPS- induced endotoxemia, fibrinogen levels increase after 24 hours, which was beyond the time frame of this study. 17 Induced normothermia may reduce DIC through an effect on the endothelium, as we found that cooling to normothermia reduced levels of vWf which is a marker of endothelial activation. 17-19 Our study cannot dissect cause from effect. Induced normothermia may inhibit consumption coagulopathy and subsequent microthrombi formation, which may have prevented endothelial damage. 17 However, this may not be in line with the finding that LPS-induced