Red blood cells, long thought to be passive bystanders in the formation of blood clots, actually play an active role in helping clots contract, according to a new collaborative study from researchers at the Perelman School of Medicine (PSOM) and Penn’s School of Engineering and Applied Science.
In these microscopic close-ups, samples of red blood cells aggregate from left to right, becoming more compact despite the absence of platelets, long thought essential to clotting.
(Image: Rustem Litvinov)
“This discovery reshapes how we understand one of the body’s most vital processes,” says Rustem Litvinov, a senior researcher at PSOM and co-author of the study. “It also opens the door to new strategies for studying and potentially treating clotting disorders that cause either excessive bleeding or dangerous clots, like those seen in strokes.”
The findings, published in Blood Advances, upend the long-standing idea that only platelets, the small cell fragments that initially plug wounds, drive clot contraction. Instead, the Penn team found that red blood cells themselves contribute to this crucial process of shrinking and stabilizing blood clots.
Until now, researchers believed that only platelets were responsible for clot contraction. These tiny cell fragments pull on rope-like strands of the protein fibrin to tighten and stabilize clots.
“Red blood cells were thought to be passive bystanders,” says co-author John Weisel, professor of cell and developmental biology at PSOM and an affiliate of the bioengineering graduate group at Penn Engineering. “We thought they were just helping the clot to make a better seal.”
To figure out how red blood cells were driving this unexpected behavior, the team turned to Prashant Purohit, professor of mechanical engineering and applied mechanics at Penn Engineering.
As blood begins to clot, a web-like protein called fibrin forms a mesh that traps red blood cells and pulls them close together. “That packing sets the stage for osmotic depletion forces to take over,” says Purohit.
Once the red blood cells are packed tightly within the fibrin mesh, proteins in the surrounding fluid are squeezed out from the narrow spaces between the cells. This creates an imbalance: the concentration of proteins is higher outside the packed cells than between them, which results in a difference in “osmotic pressure.”
That pressure difference acts like a squeeze from the outside, pushing the red blood cells even closer together. “This attraction causes the cells to aggregate and transfer mechanical forces to the fibrin network around them,” says Purohit. “The result is a stronger, more compact clot, even without the action of platelets.”
Read more at Penn Engineering Today.