Sickle Cell

Anemia
By:
Nancy Saber
Roba Shaat
Mohamed Samir El-Asaly

Under Supervision:
Prof. Dr. Aziza Mahrous
 Definition
 Genetics of SCD
 History
 Hemoglobin
 Genetics of SCD
 Inheritance of Sickle Cell Disease
 Mechanism
 Symptoms
 Complications
 Diagnosis
 Treatment
 Sickle Cell Anemia
 Is an inherited form of anemia — a condition in which
there aren't enough healthy red blood cells to carry
adequate oxygen throughout your body.

 Normally, your red blood cells are flexible and round,

moving easily through your blood vessels.
 Sickle Cell Anemia
 In sickle cell anemia, the red blood cells become rigid and
sticky and are shaped like sickles or crescent moons.
 These irregularly shaped cells can get stuck in small blood
vessels, which can slow or block blood flow and oxygen to
parts of the body.
 Definition
 Sickle Cell disease: is a genetic
disorder that affects erythrocytes
(RBC) causing them to become
sickle or crescent shaped.
 The effects of this condition due to
an abnormality of the hemoglobin
molecules found in erythrocytes.
 History
 In 1904, Walter Clement Noel traveled from Grenada
to the United States to start studying at the Chicago
College of Dental Surgery.

 A few months later he was admitted to the

Presbyterian Hospital in Chicago when he developed
severe respiratory distress and a leg ulcer, both of
which we now know are symptoms of sickle cell.

 Dr. Earnest E. Irons, the intern who was on duty that

day, performed a routine blood test and a urine
analysis for Noel and was the first to observed these
“pear shaped, elongated” sickled blood cells.
Report of blood test on Walter Clement Noel dated
31 December 1904.
 It was not until 1910 that Dr
James Herrick, the supervisor of
Dr Irons, published his article
describing these “peculiar
elongated and sickle shaped red
blood corpuscles in a case of
severe anemia.”
 This was the first documented
and recorded case of Sickle cell
in Western medicine.
 Dr Noel returned to Grenada in
1907 and ran his dental practice
in St. Georges, the capital city,
until he died at the age of 32
from the acute chest syndrome.
 1917 – Genetic basis for SCD Dr. V.
Emmel.

 The third cases of Sickle cell was

described in 1915 by Cook and Meyer in a
21-year-old woman.

 Interestingly, blood samples from both the

patient and her father, who displayed no
symptoms, showed the sickling deformity
of the red cells and three of her siblings
had died from severe anemia.

 These observations made by Dr Emmel

suggested a genetic basis for the disease
but also led to a period of confusion with
the genetics of the disease.
 1922 – Dr V.R Mason names the
disease Sickle Cell Anemia.
 Dr Mason, who observed the fourth
reported case of Sickle cell, was also
the first to call the disease “sickle
cell anemia” and to notice the
similarities between the cases.
 He also noted that all of these
patients were black, inadvertently
giving rise to the popular
misconception that sickle cell
originated from people of African
origin.
 Red Blood
Cells

Erythropoesi
Smooth and s
round

Squeeze Contains
through Erythrocytes Hemoglobin
Capillaries

Transports
No Nucleus oxygen

100 – 120
days
 Hemoglobin
 The oxygen-carrying pigment and predominant
protein in the red blood cells.

 Hemoglobin forms an unstable, reversible bond

with oxygen.

 Oxyhemoglobin: Oxygenated ( bright red).

 Deoxyhemoglobin: Reduced ( purple-blue).

 Hemoglobin
 Each hemoglobin molecule is made up of four heme
groups surrounding a globin group.
 Heme contains iron and gives a red color to the molecule.
 Globin consists of two linked pairs of polypeptide chains.
 Genetics of SCD
 The change in cell structure arises
from a change in the structure of
hemoglobin.
 A single change in an amino acid
causes hemoglobin to aggregate.
Hemoglobin A Hemoglobin S
 Inheritance of Sickle Cell
Disease
 If one parent has sickle cell trait
(HbAS) and the other does not
carry the sickle hemoglobin at all
(HbAA) then none of the children
will have sickle cell anemia.

 There is a one in two (50%)

chance that any given child will get
one copy of the HbAS gene and
therefore have the sickle cell trait.

 It is equally likely that any given

child will get two HbAA genes and
be completely unaffected.
 Inheritance of Sickle Cell
Disease
 If both parents have sickle cell
trait (HbAS) there is a one in
four (25%) chance that any
given child could be born with
sickle cell anemia.

 There is also a one in four

chance that any given child
could be completely unaffected.

 There is a one in two (50%)

chance that any given child will
get the sickle cell trait.
 Inheritance of Sickle Cell
Disease
 If one parent has sickle cell
trait (HbAS) and the other has
sickle cell anemia (HbSS)
there is a one in two (50%)
chance that any given child
will get sickle cell trait and a
one in two (50%) chance that
any given child will get sickle
cell anemia.

 No children will be completely

unaffected.
 Inheritance of Sickle Cell
Disease
 If one parent has sickle cell
anemia (HbSS) and the other is
completely unaffected (HbAA)
then all the children will have
sickle cell trait.

 None will have sickle cell

anemia.

 The parent who has sickle cell

anemia (HbSS) can only pass
the sickle hemoglobin gene to
each of their children.
 Mechanism
 When sickle hemoglobin (HbS) gives up its
oxygen to the tissues, HbS sticks together
 Forms long rods form inside RBC
 RBC become rigid, inflexible, and sickle-shaped
 Unable to squeeze through small blood vessels,
instead blocks small blood vessels
 Less oxygen to tissues of body

 RBCs containing HbS have a shorter lifespan

 Normally 20 days
 Chronic state of anemia
 Symptoms
They vary from person to person and
change over time, include:
 Anemia. Sickle cells break apart
easily and die, leaving you without
enough red blood cells. Red blood
cells usually live for about 120 days
before they need to be replaced. But
sickle cells usually die in 10 to 20
days, leaving a shortage of red blood
cells (anemia). Without enough red
blood cells, your body can't get the
oxygen it needs to feel energized,
causing fatigue.
 Symptoms
 Episodes of pain. Periodic episodes of pain, called crises,
are a major symptom of sickle cell anemia.
 Pain develops when sickle-shaped red blood cells block blood
flow through tiny blood vessels to your chest, abdomen and
joints. Pain can also occur in your bones.
 The pain varies in intensity and can last for a few hours to a
few weeks. Some people have only a few pain episodes.
Others have a dozen or more crises a year. If a crisis is
severe enough, you might need to be hospitalized. Some
adolescents and adults with sickle cell anemia also have
chronic pain, which can result from bone and joint damage,
ulcers and other causes.
 Symptoms
 Painful swelling of hands and
feet. The swelling is caused by
sickle-shaped red blood cells
blocking blood flow to the hands and
feet.
 Frequent infections. Sickle cells
can damage an organ that fights
infection (spleen), leaving you more
vulnerable to infections. Doctors
commonly give infants and children
with sickle cell anemia vaccinations
and antibiotics to prevent potentially
life-threatening infections, such as
pneumonia.
 Symptoms
 Delayed growth. Red blood
cells provide your body with the
oxygen and nutrients you need
for growth. A shortage of
healthy red blood cells can slow
growth in infants and children
and delay puberty in teenagers.
 Vision problems. Tiny blood
vessels that supply your eyes
may become plugged with sickle
cells. This can damage the retina
— the portion of the eye that
processes visual images, leading
to vision problems.
 Complications
Sickle cell anemia can lead to a host of complications, including:

 Stroke. A stroke can occur if sickle cells block blood flow to an area of
your brain. Signs of stroke include seizures, weakness or numbness of
your arms and legs, sudden speech difficulties, and loss of
consciousness. If your baby or child has any of these signs and
symptoms, seek medical treatment immediately. A stroke can be fatal.

 Acute chest syndrome. This life-threatening complication causes chest

pain, fever and difficulty breathing. Acute chest syndrome can be caused
by a lung infection or by sickle cells blocking blood vessels in your lungs.
It might require emergency medical treatment with antibiotics and other
treatments.

 Pulmonary hypertension. People with sickle cell anemia can develop

high blood pressure in their lungs (pulmonary hypertension). This
complication usually affects adults rather than children. Shortness of
breath and fatigue are common symptoms of this condition, which can
be fatal.
 Complications
 Organ damage. Sickle cells that block blood flow through
blood vessels immediately deprive the affected organ of
blood and oxygen. In sickle cell anemia, blood is also
chronically low on oxygen. Chronic deprivation of oxygen-rich
blood can damage nerves and organs in your body, including
your kidneys, liver and spleen. Organ damage can be fatal.

 Blindness. Sickle cells can block tiny blood vessels that

supply your eyes. Over time, this can damage the portion of
the eye that processes visual images (retina) and lead to
blindness.

 Leg ulcers. Sickle cell anemia can cause open sores, called
ulcers, on your legs.

 Gallstones. The breakdown of red blood cells produces a

substance called bilirubin. A high level of bilirubin in your
body can lead to gallstones.
 Diagnosis
 A blood test can check for hemoglobin S — the defective
form of hemoglobin that underlies sickle cell anemia. In the
United States, this blood test is part of routine newborn
screening done at the hospital. But older children and adults
can be tested, too.
 In adults, a blood sample is drawn from a vein in the arm. In
young children and babies, the blood sample is usually
collected from a finger or heel.
 If the screening test is negative, there is no sickle cell gene
present.
 If the screening test is positive, further tests will be done to
determine whether one or two sickle cell genes are present.
 Check for a low red blood cell count (anemia) will be done.
 Genetic counseling
 Two tests can be used to help expectant parents find out if
their child is affected.
1. Amniocentesis, done usually at 14-16 weeks of pregnancy,
tests a sample of the amniotic fluid in the womb for genetic
defects (the fluid and the fetus have the same DNA). Under
local anesthesia, a thin needle is inserted through the
woman's abdomen and into the womb. About 20 milliliters
of fluid (roughly 4 teaspoons) is withdrawn and sent to a lab
for evaluation. Test results often take 1-2 weeks.
 Genetic counseling
2. Chorionic villus sampling, or CVS, involves the removal and
testing of a very small sample of the placenta during early
pregnancy. The sample, which contains the same DNA as
the fetus, is removed by catheter or a fine needle inserted
through the cervix or by a fine needle inserted through the
abdomen. The tissue is tested for genetic changes
identified in an affected family member. Results are usually
available within 2 weeks.
 Treatment
 Treatment is usually aimed at avoiding crises, relieving
symptoms and preventing complications. Babies and
children age 2 and younger with sickle cell anemia should
make frequent visits to a doctor.

 Children older than 2 and adults with sickle cell anemia

should see a doctor at least once a year, according to the
Centers for Disease Control and Prevention.

 Treatments might include medications to reduce pain and

prevent complications, and blood transfusions, as well as
a bone marrow transplant.
 Medications
 Antibiotics. Children with sickle cell
anemia may begin taking the
antibiotic penicillin when they're
about 2 months old and continue
taking it until they're at least 5 years
old.
 Doing so helps prevent infections,
such as pneumonia, which can be life-
threatening to an infant or child with
sickle cell anemia.
 As an adult, if you've had your spleen
removed or had pneumonia, you
might need to take penicillin
throughout your life.
 Medications
 Pain-relieving medications. To relieve pain
during a sickle cell crisis.

 Hydroxyurea (Droxia, Hydrea). When

taken daily, hydroxyurea reduces the
frequency of painful crises and might reduce
the need for blood transfusions and
hospitalizations.

 Hydroxyurea seems to work by stimulating

 Treatment
Assessing stroke risk
 Using a special ultrasound machine
(transcranial), doctors can learn which
children have a higher risk of stroke.
This painless test, which uses sound
waves to measure blood flow, can be
used on children as young as 2 years.
Regular blood transfusions can
decrease stroke risk.
Vaccinations to prevent infections
 Childhood vaccinations are important
for preventing disease in all children.
 Vaccinations, such as the pneumococcal
vaccine and the annual flu shot, are
also important for adults with sickle cell
anemia.
 Treatment
Blood transfusions
 In a red blood cell transfusion, red blood cells are removed
from a supply of donated blood, then given intravenously to
a person with sickle cell anemia.
 Blood transfusions increase the number of normal red blood
cells in circulation, helping to relieve anemia. In children with
sickle cell anemia at high risk of stroke, regular blood
transfusions can decrease the risk. Transfusions can also be
used to treat other complications of sickle cell anemia, or
they can be given to prevent complications.
 Blood transfusions carry some risk, including infection and
excess iron buildup in your body. Because excess iron can
damage your heart, liver and other organs, people who
undergo regular transfusions might need treatment to reduce
iron levels.
 Treatment
 Nitric oxide. People with
sickle cell anemia have low
levels of nitric oxide in their
blood.
 Nitric oxide is a gas that helps
keep blood vessels open and
reduces the stickiness of red
blood cells. Treatment with
inhaled nitric oxide might
prevent sickle cells from
clumping together.
 Studies on nitric oxide have
shown little benefit so far.
 Bone Marrow Transplant
 Bone marrow transplant, also known as
stem cell transplant, offers the only
potential cure for sickle cell anemia. It's
usually reserved for people younger than
age 16 because the risks increase for
people older than 16. Finding a donor is
difficult, and the procedure has serious
risks associated with it, including death.

 A bone marrow transplant involves

replacing bone marrow affected by sickle
cell anemia with healthy bone marrow
from a donor. The procedure usually uses
a matched donor, such as a sibling, who
doesn't have sickle cell anemia. For many,
donors aren't available. But stem cells
from umbilical cord blood might be an
option.
 Bone Marrow Transplant
 Because of the risks associated with a bone marrow transplant,
the procedure is recommended only for people, usually children,
who have significant symptoms and problems from sickle cell
anemia.

 If a donor is found, the person with sickle cell anemia receives

radiation or chemotherapy to destroy or reduce his or her bone
marrow stem cells. Healthy stem cells from the donor are
injected intravenously into the bloodstream of the person with
sickle cell anemia, where they migrate to the bone marrow and
begin generating new blood cells.

 The procedure requires a lengthy hospital stay. After the

transplant, you'll receive drugs to help prevent rejection of the
donated stem cells. Even so, your body might reject the
transplant, leading to life-threatening complications.
 Experimental treatments
Scientists are studying new treatments
for sickle cell anemia, including:
 Gene therapy. Researchers are
exploring whether inserting a normal
gene into the bone marrow of people
with sickle cell anemia will result in
normal hemoglobin.
 Scientists are also exploring the
possibility of turning off the defective
gene while reactivating another gene
responsible for the production of fetal
hemoglobin — a type of hemoglobin
found in newborns that prevents
sickle cells from forming. Potential
treatments using gene therapy are a
long way off, however.
 Experimental treatments
 Although several of the initial
hurdles to SCD gene therapy
appear to have been overcome,
it is prudent to recognize
barriers that remain.
 Efficient transduction of HSCs
with lentiviral vectors has
become increasingly reliable, but
the complicated components of
many globin vectors present
unique challenges for production
of high-titer virus capable of
robust transduction.
 Experimental treatments
 Scaling up procedures to multiple patients is a
nontrivial challenge.
 Safety and efficacy can only be established by
careful clinical trials with extended patient
follow-up.
 Gene engineering methods are rapidly evolving
and should facilitate development of “second-
generation” gene therapy approaches in the
coming years. After many years of preclinical
laboratory investigation, gene therapy options
are now on the horizon for patients with SCD.