- In a sickle-cell disease complication known as vaso-occlusive
crisis, the misshaped red blood cells tend to adhere to blood vessels
decreasing oxygen delivery and causing acute pain
- A new study sheds light on how these crises
- The findings hope to be able to predict when,
such a crisis might occur
A new study
from MIT has explained how and why sickled red blood cells in sickle-cell
disease or SCD stick to blood vessels.
One common painful complication of sickle-cell
disease is known as vaso-occlusive crisis or sickle-cell crisis
. It is initiated when
deformed or sickled red blood cells (RBCs) clump
together and block or occlude tiny blood vessels
. This action causes acute episodes of severe pain
(crisis) and swelling in the affected body parts.
The acute pain that occurs is a common reason why SCD patients seek medical
care in hospital emergency departments. They are treated with opioids or other
‘A complication of sickle-cell disease called vaso-occlusive crisis results in acute pain in patients. Researchers have now found out how the crisis occurs and may be on the path to prevent it.’
painful crises are very much unpredictable. In a sense, we understand why they
happen, but we don't have a good way to predict them yet," says Ming Dao,
a principal research scientist in MIT's Department of Materials Science and
Engineering and one of the senior authors of the study.
The protein hemoglobin (Hb) in red blood cells is
responsible for carrying oxygen throughout the body
. When a single mutation
occurs in the gene that codes for Hb, the red blood cells which are usually
disc-shaped become sickle-shaped, especially in low oxygen conditions. Hence
the condition is known as sickle-cell disease
patients often suffer from vaso-occlusive crisis and anemia
since the changed Hb cannot carry as much.
Study - To understand how the RBCs interact with
blood vessels to cause the vaso-occlusive crisis
The team of
scientists designed a specialized
microfluidic system that would simulate the post-capillary vessels
These vessels inherently
carry oxygen-deprived blood away from the capillaries, are about 10-20 microns
in diameter, and are the most common sites for vaso-occlusions.
designed the system in such a way that they could control the
When they created very low oxygen levels, otherwise known as hypoxia
similar to what is seen in post-capillary vessels, they found that sickle-cells
became two to four times more prone to stick to the blood vessel walls than
they were at normal oxygen levels.
is when oxygen is low, hemoglobin present in sickle cells forms stiff fibers
that become larger and push the cell membrane outward as well as helping the
cells to stick more firmly to the blood vessel lining.
has been little understanding of why, under hypoxia, there is much more
adhesion," says Subra Suresh, president of Singapore's Nanyang
Technological University, former dean of engineering at MIT, and the Vannevar
Bush Professor Emeritus of Engineering. "The experiments of this study
provide some key insights into the processes and mechanisms responsible for
discovery made by the researchers was that in SCD patients, the cells that are
most likely to adhere to blood vessels are
the immature red blood cells called reticulocytes
. The reason being younger
sickle red cells, just released from bone marrow, have greater cell membrane
surface area than mature red blood cells, which allows them to create more
observed the growth of sickle hemoglobin fibers stretching reticulocytes within
minutes," says lead author and MIT postdoc Dimitrios Papageorgiou.
"It looks like they're trying to grab more of the surface and adhere more
researchers had studied how long it takes the blood cells from the SCD patients
to stiffen so that they become more likely to block blood flow in the tiny
researchers want to combine their earlier study with the current findings on
adhesion and devise a complete model of vaso-occlusion.
does not occur with all SCD patients, and the patients who experience it have
different frequencies of attacks. Hence, the MIT researchers hope their findings
would help them predict crises for individual patients that would help to give
- Sickle Cell Disease - (https://kidshealth.org/en/teens/sickle-cell-anemia.html)