Differences in red blood cell stiffness may explain variations in SCD severity
Study: Findings could spur development of more effective, personalized therapies
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Differences in the stiffness of red blood cells may help to explain variations in the severity of sickle cell disease (SCD), according to a new study.
The findings shed new light on the physics that govern the flow of deformed blood cells through vessels. Researchers found that stiff cells tend to be shunted to the edges of vessels, and when there are enough of them, they can form a jam that drastically interferes with blood flow.
“I am really excited we were able to provide greater insight into the physical mechanisms driving the disease,” Hannah Szafraniec, the study’s first author at the University of Minnesota, said in a university news story. “This could help the field develop more effective, personalized therapies and new testing that can give early warning for symptoms of sickle cell disease.”
The study, “Suspension physics govern the multiscale dynamics of blood flow in sickle cell disease,” was published in Science Advances by a team of researchers in the U.S. and the U.K.
Deformed cells prone to creating blockages
Red blood cells are responsible for ferrying oxygen throughout the body. They do so with the help of a protein called hemoglobin. Normally, red blood cells are disk-shaped and flexible, allowing them to glide through the body’s blood vessels like inner tubes drifting down a lazy river.
But in sickle cell disease, the production of an abnormal hemoglobin protein causes red blood cells in the presence of low oxygen levels to acquire the sickle shape that gives the disease its name. These deformed cells are stiffer and stickier than normal, and they are prone to forming blockages that can lead to SCD complications, such as vaso-occlusive crises.
Although it’s established that sickled red blood cells can cause blood vessel blockages in people with SCD, the disease affects everyone differently, and the reasons for this variation aren’t fully understood.
“For example, it remains unclear why individuals with SCD exhibit highly variable blood rheology, which is linked to certain clinical complications,” the researchers wrote. Blood rheology refers to the flow and deformation behavior of blood and its formed elements, including red blood cells.
“We do not understand how the presence of stiff RBCs [red blood cells] affects local blood flow in the microvasculature, where most of the [circulation-driven disease processes], such as vaso-occlusive crisis, are thought to occur,” the researchers added.
Researchers develop platforms to track physics of blood cell flow
With this study, the team sought to better understand how SCD affects blood rheology. To do this, they developed microfluidic platforms to measure red blood cell properties and flow in blood samples from SCD patients. These platforms essentially create artificial blood vessels that the researchers can use to carefully track the physics of blood cell flow.
The results indicate that blood flow is governed almost entirely by the activity of a small population of very stiff red blood cells. The researchers found that mathematical models based only on the activity of these stiff cells predicted the overall flow of red blood cells with near-perfect accuracy.
“Our work bridges the gap between how single cells behave and how the entire blood supply flows,” said David Wood, PhD, the study’s senior author at the University of Minnesota. “By using an engineering approach to measure both individual cell properties and whole blood dynamics, we found that patients with very different clinical profiles all follow the same underlying physical relationship governed by the fraction of stiff cells.”
Based on their models, the researchers determined that, as these stiff cells flow through vessels, they tend to bump into the vessel walls. And when levels of these stiff cells get high enough, they can suddenly form a jam, impeding blood flow.
Our work bridges the gap between how single cells behave and how the entire blood supply flows.
The scientists said that this discovery could help explain why SCD affects people differently — the data imply that variations in the stiffness of small numbers of blood cells could account for these differences. The results also underscore the importance of considering how the disease affects individual red blood cells, rather than focusing on average measures across all cells.
“These findings further motivate the need for single RBC measurements for assessing and optimizing therapeutic strategies for individuals with SCD,” the researchers wrote.
They said their blood flow platform could also be used to help better understand blood cell dynamics in other disorders, writing: “Evaluating [disease-causing] rheology as it relates to [variability] in the properties of RBCs is likely relevant for a range of diseases, and the results here provide a framework to understand how [disease features] may evolve across those diseases.”
