Researchers at Oregon Health & Science University have made a groundbreaking discovery regarding a molecule found on certain bacteria that may drive blood clotting in sepsis, a life-threatening condition responsible for approximately 8 million deaths annually.
The team at OHSU’s cardiovascular engineering lab has been delving into the specific mechanisms of blood clotting in sepsis, aiming to enhance treatments for critically ill patients. Owen McCarty, Ph.D., the senior author of the research paper and a professor of biomedical engineering at the OHSU School of Medicine, explained that the immune response to bacteria can become uncontrolled.
In a normal scenario, blood forms small clots to contain bacteria and clear them from the bloodstream. However, if there is an abundance of bacteria, the system becomes overwhelmed, depleting platelets and clotting factors. This leads to a catastrophic situation where clotting and bleeding cannot be controlled.
The latest study conducted by the team, published in the Journal of Biological Chemistry, focused on lipopolysaccharide (LPS), a molecule present on certain bacteria like E. coli. The researchers discovered that LPS can directly activate proteins in the blood that initiate clotting, obstructing blood flow and causing damage to vital organs.
This process, known as the “contact pathway,” involves a series of reactions where blood proteins collaborate to form clots. The team identified that a specific type of LPS, O26:B6, is particularly effective at triggering this reaction, increasing the likelihood of clotting issues.
Sepsis is a severe condition where the body’s response to an infection goes haywire, resulting in widespread inflammation, organ failure, and complications such as excessive blood clotting. Gram-negative bacteria, including E. coli, are common culprits in sepsis as they release LPS when invading the bloodstream.
Joseph Shatzel, M.D., a physician-scientist at OHSU specializing in clotting and bleeding disorders, emphasized the challenges of treating sepsis. The team’s focus on the contact activation system, a part of the clotting system often overlooked, has led to innovative approaches that could revolutionize sepsis treatment.
The researchers are now working on experimental treatments targeting factor XII, a coagulating protein that plays a crucial role in the clotting process. By developing antibodies to block factor XII activity, the team aims to prevent dangerous clots in sepsis patients without increasing the risk of bleeding.
The interdisciplinary nature of the team at OHSU, combining basic scientists like André L. Lira and clinicians like Joseph Shatzel, has been instrumental in driving their innovative work forward. The collaborative environment at OHSU has facilitated the seamless transition from lab research to patient care, enabling groundbreaking discoveries in the field of sepsis treatment.
The team’s ongoing studies and grant applications signal a promising future for sepsis treatment. With a strong focus on precision therapies and targeted interventions, the researchers at OHSU are dedicated to improving outcomes for sepsis patients and potentially revolutionizing the field of critical care medicine.
