Purple blood cells, lengthy regarded as passive bystanders within the formation of blood clots, truly play an energetic position in serving to clots contract, in line with a brand new examine by researchers on the College of Pennsylvania.
“This discovery reshapes how we perceive one of many physique’s most important processes,” says Rustem Litvinov, a senior researcher on the Perelman Faculty of Medication (PSOM) and co-author of the examine. “It additionally opens the door to new methods for learning and doubtlessly treating clotting issues that trigger both extreme bleeding or harmful clots, like these seen in strokes.”
The discovering, revealed in Blood Advances, upends the long-standing concept that solely platelets, the small cell fragments that originally plug wounds, drive clot contraction. As a substitute, the Penn group discovered that purple blood cells themselves contribute to this significant strategy of shrinking and stabilizing blood clots.
“Purple blood cells have been studied because the seventeenth century,” says co-author Prashant Purohit, Professor of Mechanical Engineering and Utilized Mechanics inside Penn Engineering. “The shocking truth is that we’re nonetheless discovering out new issues about them within the twenty first century.”
An surprising discovering
Till now, researchers believed that solely platelets have been liable for clot contraction. These tiny cell fragments pull on rope-like strands of the protein fibrin to tighten and stabilize clots.
“Purple blood cells have been regarded as passive bystanders,” says co-author John Weisel, Professor of Cell and Developmental Biology inside PSOM and an affiliate of the Bioengineering graduate group inside Penn Engineering. “We thought they have been simply serving to the clot to make a greater seal.”
That assumption started to unravel when Weisel and Litvinov ran a check they anticipated to fail. They created blood clots with out platelets. “We anticipated nothing to occur,” says Weisel. “As a substitute, the clots shrank by greater than 20%.”
To double-check their outcomes, the group repeated the experiment utilizing common blood handled with chemical substances to dam platelet exercise. The clots nonetheless contracted. “That is after we realized purple blood cells have to be doing extra than simply taking on house,” says Litvinov.
Modeling the mechanics of blood clots
To determine how purple blood cells have been driving this surprising habits, the group turned to Purohit, a mechanical engineer by coaching.
An skilled on comfortable supplies like blood clots and gels, Purohit developed a mathematical mannequin that steered that purple blood cells compact collectively primarily on account of “osmotic depletion.”
This course of additionally explains how particles in colloids—mixtures like paint, milk or muddy water—can collect and type clusters when the circumstances round them change.
“Basically, the proteins within the surrounding fluid create an imbalance in strain that pushes purple blood cells collectively,” says Purohit. “This engaging power causes them to pack extra tightly, serving to the clot contract even with out platelets.”
How clotting works with out platelets
As blood begins to clot, a web-like protein referred to as fibrin varieties a mesh that traps purple blood cells and pulls them shut collectively. “That packing units the stage for osmotic depletion forces to take over,” says Purohit.
As soon as the purple blood cells are packed tightly inside the fibrin mesh, proteins within the surrounding fluid are squeezed out from the slim areas between the cells. This creates an imbalance: The focus of proteins is larger outdoors the packed cells than between them, which ends up in a distinction in “osmotic strain.”
That strain distinction acts like a squeeze from the surface, pushing the purple blood cells even nearer collectively.
“This attraction causes the cells to mixture and switch mechanical forces to the fibrin community round them,” provides Purohit. “The result’s a stronger, extra compact clot, even with out the motion of platelets.”
Validating the mannequin
Prior analysis steered one other doable rationalization: bridging, during which the attraction between small molecules on the floor of purple blood cells causes them to stick.
“Our mannequin steered the bridging impact was actual,” says Purohit, “however a lot smaller than the impact of osmotic depletion.”
To check the mannequin, first creator Alina Peshkova, now a postdoctoral researcher in Pharmacology inside PSOM, carried out a sequence of experiments on modified blood clots.
Within the absence of the molecules that trigger the bridging impact, the clots nonetheless contracted, however little contraction occurred in an atmosphere designed to stop osmotic depletion.
“We experimentally confirmed what the mannequin predicted,” says Peshkova. “It is an instance of idea and apply coming collectively to assist one another.”
Combating clotting illnesses and strokes
Gaining a greater understanding of the position purple blood cells play within the formation and maturation of clots might result in new therapies for circumstances like thrombocytopenia, during which low platelet counts may cause uncontrolled bleeding.
The findings might additionally make clear how clots break into fragments that journey by the bloodstream and trigger blockages—referred to as embolisms—that may set off strokes.
“Finally, our mannequin goes to be useful in understanding, stopping and treating illnesses associated to clotting contained in the bloodstream,” says Purohit.
Extra co-authors embody Ekaterina Ok. Rednikova, Rafael R. Khismatullin and Vladimir R. Muzykantov of PSOM, and Oleg V. Kim of PSOM and Virginia Tech.
Extra info:
Alina D. Peshkova et al, Purple blood cell aggregation inside a blood clot causes platelet-independent clot shrinkage, Blood Advances (2025). DOI: 10.1182/bloodadvances.2024015533
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Purple blood cells drive blood clot shrinkage, overturning outdated assumptions (2025, August 6)
retrieved 6 August 2025
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