Known as one of the leading causes of deaths in hospitals worldwide, sepsis is a common ending for patients with pneumonia, cancer, heart disease, and HIV.

It is also responsible for the lethality of many hospital-acquired infections such as multi-drug resistant MRSA (methicillin resistant Staphylococcus aureus), which claims the lives of relatively young and healthy individuals. During sepsis, which refers to a systemic poisoning of the blood as a result of infection or advanced disease, toxins invade the bloodstream, and multiple organs, such as the heart, lungs and kidneys, begin to fail. Understanding the underlying causes of sepsis is critical to developing effective means of intervention.

Aberrant blood clotting contributes to death from sepsis. Our investigators have shown that clotting normally helps prevent bleeding as infected cells are killed and removed from the body. During sepsis, however, clotting often goes into overdrive, exacerbating inflammation and depriving tissues of necessary nutrients and oxygen. In some situations, such as during infection by Ebola virus, the clotting system can also exhaust itself, resulting in a failure to clot.

Understanding the mechanisms that regulate the body’s clotting system could also impact the effectiveness of transplant surgeries, since transplant rejection often is associated with excessive activation of the blood-clotting system.

Research performed at the Trudeau Institute has identified several clotting proteins that appear to be abnormally active during sepsis. Using research models, our scientists are interfering with these proteins (tamping down their activity) to see if normal clotting can be restored. If so, these proteins should provide good entry points for the development of drugs to inhibit clotting during sepsis in human patients.