One reason sepsis is difficult to treat is that the excessive inflammatory response prompts changes in another powerful system of our bodies, the blood clotting system. Blood is supposed to clot in response to trauma, as a means to prevent bleeding. However, the excessive inflammation that accompanies sepsis causes blood to clot within our blood vessels, even in the absence of trauma, thereby blocking blood flow and starving tissues of life-giving oxygen. It seems logical to treat sepsis patients with drugs that stop blood clotting (i.e. anticoagulants). However, anticoagulant therapies have largely failed to extend the lives of patients with sepsis. The Trudeau study provides a dramatic demonstration of the importance of the blood clotting process during sepsis, thus helping to explain why anticoagulants typically fail to help sepsis patients.
Additionally, the Trudeau study identified a number of molecular players key to regulating the levels of fibrin produced by the protective blood clotting pathway. The Smiley lab hypothesizes that drugs for sepsis will need to maintain these protective pathways, while preventing the excessive, oxygen-depriving, blood clotting that causes organ failure. Importantly, they identified at least one drug target that may allow them to selectively prevent the damaging blood clots while maintaining the protective fibrin. Specifically, they showed that the "extrinsic" blood clotting pathway is critical for protective clotting during sepsis whereas the "intrinsic" pathway appears to be dispensable. Ongoing studies aim to assess whether anticoagulant drugs that selectively block this intrinsic pathway will help to prevent deaths from infections that cause sepsis.
|Contact: Karen Sharma|