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.
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.
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.
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
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.