Sickle Cell Disease
Sickle cell disease is an inherited genetic
abnormality of hemoglobin (the oxygen-carrying protein found in red blood
cells) characterized by sickle (crescent)-shaped red blood cells and chronic
anemia caused by excessive destruction of the abnormal red blood cells.
People always have anemia and sometimes
jaundice.
Worsening anemia, fever, and shortness of
breath with pain in the long bones, abdomen, and chest can indicate sickle cell
crisis.
A special blood test called electrophoresis
can be used to determine whether people have sickle cell disease.
Avoiding activities that may cause crises
and treating infections and other disorders quickly can help prevent crises.
Sickle cell disease affects people with
African or Black American ancestry almost exclusively. About 10% of people with
such ancestry in the United States have one copy of the gene for sickle cell
disease (that is, they have sickle cell trait). People who have sickle cell
trait do not develop sickle cell disease, but they do have increased risks of
some complications such as blood in their urine. About 0.3% of people with
African or Black American ancestry have two copies of the gene. These people
develop the disease.
Red Blood Cell Shapes
Normal red blood cells are flexible and
disk-shaped, thicker at the edges than in the middle. In several hereditary
disorders, red blood cells become spherical (in hereditary spherocytosis), oval
(in hereditary elliptocytosis), or sickle-shaped (in sickle cell disease).
Red Blood Cell Shapes
In sickle cell disease, the red blood cells
contain an abnormal form of hemoglobin (the protein that carries oxygen). The
abnormal form of hemoglobin is called hemoglobin S. When red blood cells
contain a large amount of hemoglobin S, they can become deformed into a sickle
shape and less flexible. Not every red blood cell is sickle-shaped. The
sickle-shaped cells become more numerous when people have infections or low
levels of oxygen in the blood.
The sickle cells are fragile and break
apart easily. Because the sickle cells are stiff, they have difficulty
traveling through the smallest blood vessels (capillaries), blocking blood flow
and reducing oxygen supply to tissues in areas where capillaries are blocked.
The blockage of blood flow can cause pain and, over time, cause damage to the
spleen, kidneys, brain, bones, and other organs. Kidney failure and heart
failure may occur.
Symptoms of Sickle Cell Disease
People who have sickle cell disease always
have some degree of anemia (often causing fatigue, weakness, and paleness) and
may have mild jaundice (yellowing of the skin and whites of the eyes). Some
people have few other symptoms. Others have severe, recurring symptoms that
cause enormous disability and early death.
Sickle cell trait
In people with sickle cell trait, red blood
cells are not fragile and do not break easily. Sickle cell trait does not cause
painful crises, but rarely, people die suddenly while undergoing very strenuous
exercise that causes severe dehydration, such as during military or athletic
training.
People with sickle cell trait are at
increased risk of chronic kidney disease and pulmonary embolism. Rarely, they
may notice blood in their urine. People with sickle cell trait are also at risk
for an extremely rare form of kidney cancer.
Sickle cell crisis
Anything that reduces the amount of oxygen
in the blood, such as vigorous exercise, mountain climbing, flying at high
altitudes without sufficient oxygen, or an illness, may bring on a sickle cell
crisis (also called an exacerbation). A sickle cell pain (vaso-occlusive)
crisis is an episode of increased symptoms and can consist of a sudden
worsening of anemia, pain (often in the abdomen or long bones of the arms and
legs), fever, and sometimes shortness of breath. Abdominal pain may be severe,
and vomiting may occur. Sometimes, additional complications occur with a pain
crisis, including
Aplastic crisis: Production of red blood
cells in the bone marrow stops during infection with some viruses
Acute chest syndrome: Caused by blockage of
capillaries in the lungs
Acute splenic or hepatic (liver)
sequestration (a large accumulation of cells in an organ): Rapid enlargement of
the spleen or liver
Acute chest syndrome can occur in people of
all ages, but it is most common among children. It is usually characterized by
severe pain and difficulty breathing. Acute chest syndrome can be fatal.
In children, acute sequestration of sickled
cells in the spleen (sequestration crisis) may occur causing an enlarged spleen
and worsening anemia. Acute hepatic (liver) sequestration is less common and
can occur at any age.
Complications
Most people who have sickle cell disease
develop an enlarged spleen during childhood because sickled cells become
trapped in the spleen. By the time the person reaches adolescence, the spleen
is often so badly injured that it shrinks and no longer functions. Because the
spleen helps fight infection, people with sickle cell disease are more likely
to develop pneumococcal pneumonia and other infections. Viral infections, in
particular, can decrease red blood cell production, so anemia becomes more
severe.
The liver can become progressively larger
throughout life (causing upper abdominal fullness), and gallstones often form
from the pigment of broken-apart red blood cells.
The heart usually enlarges, and an enlarged
heart is less effective in pumping blood to the body, possibly leading to heart
failure. Heart murmurs are common.
Children who have sickle cell disease often
have a relatively short torso but long arms, legs, fingers, and toes. Changes
in the bones and bone marrow may cause bone pain, especially in the hands and
feet. Episodes of joint pain with fever may occur, and the hip joint may become
so damaged that it eventually needs to be replaced.
Poor circulation to the skin may cause
sores on the legs, especially at the ankles. Young men may develop persistent,
often painful erections ( priapism). Episodes of priapism may permanently
damage the penis so that the man can no longer have erections. Blocked blood
vessels may cause strokes that damage the nervous system. In older people, lung
and kidney function may deteriorate.
Diagnosis of Sickle Cell Disease
Blood tests
Hemoglobin electrophoresis
Prenatal testing
Doctors recognize anemia, stomach and bone
pain, and nausea in a young person with African or Black American ancestry as
possible signs of a sickle cell crisis. When doctors suspect sickle cell
disease, they do blood tests. Sickle-shaped red blood cells and fragments of
destroyed red blood cells can be seen in a blood sample examined under a
microscope.
Hemoglobin electrophoresis, another blood
test, is also done. In electrophoresis, an electrical current is used to
separate the different types of hemoglobin and thus detect abnormal hemoglobin.
Further testing may be needed, depending on
the specific symptoms the person experiences during the crisis. For example, if
the person has difficulty breathing or a fever, a chest x-ray may be done.
Screening
Blood tests are done on relatives of people
with the disorder because they also may have sickle cell disease or trait.
Discovering the trait in people may be important for family planning, to
determine their risk of having a child with sickle cell disease.
In the United States, newborns are routinely
screened with a blood test.
Tests can be done during early pregnancy to
screen the fetus and allow prenatal counseling for couples who are at risk of
having a child with sickle cell disease. Fetal cells obtained through
amniocentesis or chorionic villus sampling are tested for the presence of the
sickle cell gene.
Treatment of Sickle Cell Disease
Treatments aimed at preventing crises
Treatment of crises and conditions that
cause them
Treatment is aimed at
Preventing crises
Controlling the anemia
Relieving symptoms
Stem cell transplantation may cure sickle
cell disease. Bone marrow or stem cells from a family member or other donor who
does not have the sickle cell gene may be transplanted in a person with the
disease. Although such transplantation may be curative, it is risky and so it
is not often done. Recipients must take drugs that suppress the immune system
for the rest of their life.
Gene therapy, a technique in which normal
genes are implanted in precursor cells (cells that produce blood cells), is
being studied.
Preventing sickle cell crisis
People who have sickle cell disease should
try to avoid activities that reduce the amount of oxygen in their blood and
should seek prompt medical attention for even minor illnesses, such as viral
infections. Because people are at increased risk of infection, they should
receive vaccines for pneumococcal, meningococcal, influenza, and Haemophilus influenzae
type b infections. Children typically take penicillin by mouth from age 4
months until age 6 years.
Drugs can help control sickle cell disease. For example, hydroxyurea increases the production of a form of hemoglobin found predominantly in fetuses, which decreases the number of red blood cells becoming sickle-shaped. Therefore, it reduces the frequency of sickle cell crises and acute chest syndrome. New drugs that help control the symptoms and complications of sickle cell disease are L-glutamine, crizanlizumab, and voxelotor.
Controlling anemia
People are given folic acid, a vitamin that
helps the body make new red blood cells.
Blood transfusions may be given to correct
the anemia.
Treating sickle cell crisis
Sickle cell crisis may require hospitalization.
People are given oxygen, fluid by vein (intravenously), and drugs to relieve
pain. Blood transfusions and oxygen are given for anemia that is severe enough
to pose a risk of stroke, heart attack, or lung damage. Conditions that may
have caused the crisis, such as an infection, are treated.