Lack of Amino Acid Spurs Deadly Sickle Cell Complication

laboratory microscope lens in a lab A deficiency of the amino acid arginine may contribute to the development of
pulmonary hypertension — a potentially deadly complication — in people with
sickle cell anemia, a new study suggests.

A process called hemolysis, in which red blood cells rupture, is what causes
the arginine deficiency, researchers said.

“Within the red blood cell, there is a high concentration of an
arginine-consuming enzyme called arginase,” said the study’s lead author, Dr.
Claudia Morris, the director of research for the pediatric emergency fellowship
at Children’s Hospital and Research Center in Oakland, Calif.

When arginase is released during hemolysis, explained Morris, that “triggers
a cascade of events that lead to pulmonary hypertension.”

The study findings appear in the July 6 issue of the Journal of the
American Medical Association.

Sickle cell anemia is a disease that causes red blood cells to become
sickle-shaped. This abnormal shape makes blood clots more likely, and when a
blood clot blocks a blood vessel it can cause extreme pain, according to the
National Institutes of Health (NIH). These damaged blood cells are also more
likely to break down prematurely in a process known as hemolysis. Sickle cell
disease strikes African-Americans more frequently than other racial groups.

An estimated one person of every three with sickle cell disease will
eventually develop pulmonary hypertension — high blood pressure in the arteries
of the lungs, Morris said. According to the NIH, pulmonary hypertension causes
the heart to work harder and become enlarged. Eventually, it can lead to heart
failure and death,

“It’s a life-threatening condition, and it’s what many adult sickle cell
patients die from,” she said.

For this study, Morris and her colleagues compared 228 people with sickle
cell anemia — ages 18 to 74 — to 36 healthy individuals.

The researchers measured blood amino acid levels and arginase activity. They
also tested all of the participants with sickle cell disease for pulmonary
hypertension using Doppler echocardiography — ultrasound of the lungs.

The researchers found that activity of the enzyme arginase was significantly
higher in people with sickle cell anemia than in the healthy individuals, and
those participants with pulmonary hypertension had the highest arginase
levels.

Arginase consumes an important amino acid, arginine, the researchers
explained. They found that study participants with the lowest amounts of
arginine were also 3.6 times more likely to die than those with the highest
levels of bioavailable arginine.

Arginine is normally sourced through foods such as nuts and meats. It’s also
available as a nutritional supplement, Morris said.

However, she doesn’t recommend that people with sickle cell disease start
supplementing their diet with arginine because researchers don’t know if that
will simply fuel heightened production of arginase. Instead, Morris believes
strategies that block the activity of arginase could prove more helpful.

“That would be an interesting hypothesis to test,” said Dr. Jay Brooks,
chairman of hematology and oncology at Ochsner Clinic Foundation Hospital in
Baton Rouge, La. “But, whether or not it will lead to a clinical intervention
remains to be seen.”

The findings from this study may also be useful in predicting who will
develop more severe sickle cell disease, and may eventually lead to earlier
treatments, Morris said.

“This study suggests that we may be able to identify patients who are at
greater risk of death,” she said. “This gives us a new way of thinking about
possible treatments, like nutritional supplements or inhibiting hemolysis
through transfusions.”

She added that more studies need to be done, so individuals affected by
sickle cell anemia with complications should ask their doctor about what
clinical trials might be available.

More information

To learn more about sickle cell anemia, visit the National Library of
Medicine.

SOURCES: Claudia Morris, M.D., pediatric emergency physician, and
director of research for pediatric emergency medicine fellowship, Children’s
Hospital and Research Center, Oakland, Calif.; Jay Brooks, M.D., chairman,
hematology and oncology, Ochsner Clinic Foundation Hospital, Baton Rouge, La.;
July 6, 2005, Journal of the American Medical Association

Last Updated: July 5, 2005