A team of researchers might have made the first step to predicting occurrences of vaso-occlusive pain crisis in patients born with sickle cell disease.
The study from Massachusetts Institute of Technology (MIT) analyzed blood samples from patients with the condition in a lab test that included manipulating oxygen level to look at how misshapen red blood cells will perform.
Figuring Out How To Prevent Vaso-Occlusive Pain Crises
Sickle cell disease is a genetic disorder that affects the hemoglobin or the protein in red blood cells that carries oxygen throughout the body. It is caused by a mutation that produces deformed blood cells; instead of the typical disc-shaped blood cells, patients have sickle or crescent cells.
The disorder often causes anemia (low number of red blood cells) because of the irregular hemoglobin, repeated infections, or vaso-occlusive pain crisis, which involves blood cells clumping together to block blood vessels.
"These painful crises are very much unpredictable," stated Ming Dao, one of the senior authors of the study. "In a sense, we understand why they happen, but we don't have a good way to predict them."
To find out, the researchers had to create a "specialized microfluidic system" to mimic post-capillary vessels which carry deoxygenized blood. These lab-created vessels are also made about 10-20 microns or the size in which vaso-occlusions most often occur.
Next, the team manipulated the oxygen level.
They found that lowering the oxygen increases the likelihood of vaso-occlusive pain crises. In fact, it is two to four times more likely for the sickle blood cells to stick to the wall of the blood vessel when oxygen level is low (hypoxia) than when oxygen level is normal.
The study revealed that, when oxygen is low, the hemoglobin creates fibers that grow and push the cell membrane outward to make it stick to the walls of the blood vessel.
Researchers also named reticulocytes, immature red blood cells released by the bone marrow, as likely to cause an episode of vaso-occlusive pain crisis. Because it has more cell membrane that a regular red blood cell, it sticks more easily and more firmly to the blood vessel.
"We observed the growth of sickle hemoglobin fibers stretching reticulocytes within minutes," added Dimitrios Papageorgiou, a co-lead author of the study. "It looks like they're trying to grab more of the surface and adhere more strongly."
The study sheds light on the mechanisms of how sickle red blood cells stick together and blocks a blood vessel. Because not everyone diagnosed with the disease experiences vaso-occlusive pain crisis, it is more difficult for patients and doctors to predict if and when it will happen.
Vaso-occlusive pain crisis is characterized by intense pain and swelling. It is often treated with opioid painkillers and other drugs.
Moving Forward
The researchers want to continue the research and use their recent findings with a previous study that observed how long it takes sickle cells to stiffen and block blood vessels. Together, the MIT team hopes to figure out how to predict an occurrence of vaso-occlusive pain crisis and, possibly, prevent them from happening.
The study was funded by the National Institutes of Health and was published in Proceedings of the National Academy of Sciences. Subra Suresh of Singapore's Nanyang Technological University and Vannevar Bush of MIT also served as senior authors of the study.
