According to new study, published in the journal Biomaterials by Georgia Institute of Technology and Emory University modeling the dynamics at play during clot contraction, a still poorly understood phase of blood clotting, gives fresh information on the mechanics and physics of blood clotting.
“Blood clotting is actually a physics-based phenomenon that must occur to stem bleeding after an injury,” said Wilbur A. Lam, W. Paul Bowers Research Chair in the Department of Pediatrics and the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. “The biology is known. The biochemistry is known. But how this ultimately translates into physics is an untapped area.”
That’s an issue, says Lam and his colleagues, because blood clotting is fundamentally about “how good of a seal can the body make on this damaged blood vessel to stop bleeding, or when this goes wrong, how does the body accidentally make clots in our heart vessels or in our brain?”
Platelets, small 2-micrometer cells in the blood that form the first plug, are the workhorses for stopping bleeding. The fibrin in the clot serves as a glue scaffold for the platelets to cling to and pull against. When these platelets come into contact with the fibrin scaffold, a blood clot forms. Researchers used a 3-millimeter mold filled with millions of platelets and fibrin to produce a simplified replica of a blood clot to illustrate the contraction.
“What we don’t know is, ‘How does that work?’ ‘What’s the timing of it so all these cells work together — do they all pull at the same time?’ Those are the fundamental questions that we worked together to answer,” Lam said.
To construct a computer model of a contracting clot, Lam’s team cooperated with Georgia Tech’s Complex Fluids Modeling and Simulation department, led by Alexander Alexeev, professor and Anderer Faculty Fellow at the George W. Woodruff School of Mechanical Engineering. The fibrin fibers help to create a three-dimensional network in the model, and scattered platelets can extend filopodia, or tentacle-like structures that extend from cells to connect to certain surfaces, to pull adjacent fibers.
Because platelets can only grow filopodia that are less than 6 micrometers long, the small cells could only reach neighboring fibrins when the researchers replicated a clot in which a big group of platelets were triggered at the same moment. “But in a trauma, some platelets contract first. They shrink the clot so the other platelets will see more fibrins nearby, and it effectively increases the clot force,” Alexeev explained. The force enhancement can be as high as 70% due to asynchronous platelet activity, resulting in a 90% reduction in clot volume.
“The simulations showed that the platelets work best when they’re not in total sync with each other,” Lam said. “These platelets are actually pulling at different times and by doing that they’re increasing the efficiency (of the clot).” This phenomenon, dubbed by the team asynchronous mechanical amplification, is most pronounced “when we have the right concentration of the platelets corresponding to that of healthy patients,” Alexeev said.
According to Lam, who serves young patients with blood disorders as a pediatric hematologist at Children’s Healthcare of Atlanta’s Aflac Cancer and Blood Disorders Center, the results might offer up medicinal alternatives for those with clotting concerns.
“If we know why this happens, then we have a whole new potential avenue of treatments for diseases of blood clotting,” he said, emphasizing that heart attacks and strokes occur when this biophysical process goes wrong.
“Understanding the physics of this clot contraction could potentially lead to new ways to treat bleeding problems and clotting problems.”
Sun plans to expand on the research by looking at how a single platelet force transforms or is passed to the clot force, as well as how much force is required to keep two sides of a graph together in terms of thickness and width.
Sun also plans to add red blood cells in their model, as they make up 40% of total blood and play a part in clot size determination.