The blood-clotting protein fibrinogen may hold the key to why some patients who undergo surgery to remove a diseased portion of their liver end up needing a transplant when the organ’s regeneration process doesn’t work.
“We discovered that fibrinogen accumulates within the remaining liver quickly after surgery and tells platelets to act as first responders, triggering the earliest phase of regeneration,” says study author James Luyendyk, a professor of pathobiology in the Michigan State University College of Veterinary Medicine. “But if fibrinogen or platelets are inhibited, then regeneration is delayed.”
Platelets are blood cells that help form clots and stop bleeding. When they receive information from fibrinogen, they go into action and accumulate in the remaining part of the liver to help restore it, increasing the chances of a fully functional liver and successful recovery. The liver is the only organ that can regenerate in this way.
Using samples from patients undergoing liver resection and a comparable model in mice, Luyendyk and his team noticed that when fibrinogen was low, the number of platelets in the liver decreased.
“This shows that fibrinogen deposits are extremely important and directly impact regeneration in both mice and humans,” Luyendyk says.
The findings demonstrate that fibrinogen levels could be a predictive marker for doctors, too, according to study coauthor Dafna Groeneveld, a postdoctoral research associate in Luyendyk’s lab.
“Measuring this protein in liver resection patients may help us determine in advance whether the organ will regenerate successfully or if it will become dysfunctional,” she says.
This could lead to new treatments that would help doctors correct low levels of the protein by using fibrinogen concentrates administered during surgery.
“This type of treatment hasn’t been tried in liver resection patients yet,” Luyendyk says. “But once we figure out exactly how fibrinogen works in the regeneration process and test potential therapies in mice, it could eventually provide the proof we need to bring our work into the clinic and improve patient outcomes.”
The study appears in the journal Blood. Additional researchers from the Medical University of Vienna in Austria, and the University Medical Center Groningen in the Netherlands contributed to the work.
Source: Michigan State University
