Washington University in St. Louis (WU)
The causes of DVT in trauma are known related to the triad of hypercoagulability, endothelial injury and stasis from immobility. However, clinically the formation of spontaneous DVT are known to occur at vein valves, and do not correlate with direct endothelial injury. We have preliminary data suggesting that DVT formation at valves is due to disruption of normal protective cellular mechanisms in the valve endothelium that are stimulated by oscillatory shear forces. These forces activate genes that are also regulated by pathways activated by inflammation and sepsis, suggesting sterile inflammation of trauma or endotoxin mediated gene expression in sepsis may directly cause loss of the protective phenotype, which would be consistent with clinical observation. Our project investigates the mechanisms that lead to loss of valve protective gene expression in critical illness with the aim of developing strategies for preventive therapeutic interventions besides the use of systemic anti-coagulants.