What is Sickle Cell Disease?

These days, some experimental therapies are investigating ways to

improve blood flow and reduce the number of red blood cells that get trapped inside blood
vessels, please describe in detail one of the experimental therapy for Sickle Cell Disease.

SICKLE CELL DISEASE (SCD)

1. What is “Sickle Cell Disease”?
- Sickle cell disease is a genetic disorder
(inherited through families), where red
blood cells can take the shape of a
crescent or sickle. The disease is
characterized by sickle-shaped red blood
cells. These red blood cells take on an
unusual shape, which makes it difficult for
sickle red blood cells to maneuver through
blood vessels.
- It was found in Africa, Arab, or
Mediterranean descent.
- There are several types of SCD, the most An image shows a cross-section of a standard red blood corpuscle with
normal hemoglobin. Part 2 shows abnormal, sickled red blood cells
common being sickle cell anemia (Hb SS blocking blood flow in a very vessel
Disease). Other types of sickle cell disease
are caused by different variations in
hemoglobin that in combination with
hemoglobin S may cause problems. 

2. What Causes Sickle Cell Disease?

- The cause is inherited (genetic). Sickle cell disease is caused by defective hemoglobin
which is the oxygen-carrying protein in red blood cells.
- Hemoglobin is formed of four
peptide chains each absolute to a
heme group. Different
hemoglobins have different
combinations of those chains
hemoglobin A or HbA is
created of two α-globin and two
β-globin peptide chains. This is
the primary hemoglobin affected
in sickle cell, specifically, the β
-globin chains end up misshapen.
- This is because of a mutation
within the β-globin gene or HBB
gene sickle-cell is an autosomal
recessive disease. Sickle-cell is an autosomal recessive disease so a mutation in both
copies of the beta-globin gene is needed to get the disease.
- If the person has only 1 copy of the mutation in one normal HBB gene then they are
a sickle carrier(sickle trait).

pg. 1
 - Having sickle traits does not cause health problems unless the person is exposed to
extreme conditions. What it
does do is decrease the
severity of infection by
Plasmodium falciparum
malaria so in parts of the
planet with a high malaria
burden like Africa and
pockets of southern Asia.
Those with sickle traits even
have an evolutionary
advantage this
phenomenon is named heterozygote advantage and its unfortunate consequence may be
a high rate of erythrocyte disease in people from these parts of the world.
- The sickle cell mutation is a non-conservative missense mutation that happens in the
sixth amino acid of β-globin being a valine instead of glutamic acid.
- A non-conservative substitution implies that the new amino acid or valine which is
hydrophobic has different properties than the one it replaced hydrophilic glutamic
acid.
- A hemoglobin tetramer with two α-globin and to mutate β-globin proteins is called
sickle hemoglobin or HBS. HBS carries oxygen perfectly well but when
deoxygenated, HBS changes its shape which
allows it to aggregate with other HBS proteins
and forms long polymers that distort the red
blood cell into a crescent shape - a process called
sickling.
- Conditions favorable for sickling include :
 acidosis (decreases hemoglobins affinity
for oxygen)
 small low flow vessels where red blood
cells hemoglobin molecules have plenty
of time to dump lots of oxygen molecules
- Repeated cycling of red blood cells damages their cell membranes and promotes
premature destruction since this happens within the vasculature it's called
intravascular hemolysis. This
destruction of red blood cells not
only leads to anemia which is a
deficiency in red blood cells or
loss of the normal levels of
hemoglobin but also means plenty
of hemoglobin spilling out.

3. Types Of Sickle Cell Disease:

 Sickle Cell Anemia: (SCA)
- The most common sort of SCD.

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 - Occurs when offspring inherited a hemoglobin S gene from both parents to
offer hemoglobin SS(HbSS).
- SCA tends to be the foremost serious of sickle conditions.
 Sickle Hemoglobin Disease:
- Occurs when offspring inherited a hemoglobin S gene from one parent and a hemoglobin C
gene from the other parent to give hemoglobin SC disease (HbSC).
- Milder than SCD but many of the same health problems can occur.
 Sickle β-thalassemia disease:
- Occurs when offspring inherited a hemoglobin S gene from one parent and a β-
thalassemia gene from the other parent(HbSβThal)
- The β-thalassemia gene is different from the SC gene, but it can be inherited with a
sickle gene to cause sickle β-thalassemia disease.
- In some cases a small amount of the usual Hemoglobin A is produced, in this case,
the offspring has sickle β plus-thalassemia, (HbSβ+Thal) which tends to be a mild
form of sickle cell disease.
- When no hemoglobin A is produced the condition is known as sickle beta zero
thalassemias(HbSβ° Thal). This behaves more like SC anemia.
 Sickle with hereditary persistence of fetal hemoglobin:
- Occurs when offspring inherited a hemoglobin S gene from one parent and a persisting
hemoglobin F gene from the other parent. (HbS/HPFH)
- Very rarely causes any health problems.
 Sickle hemoglobin D disease:
- An unusual form of SCD.
- Occurs when offspring inherited hemoglobin S from one parent and hemoglobin D
from the other parent(HbSD)
- Can be as serious as SCA but could be milder.

4. Who Is Affected By Sickle Cell Disease?

- It is estimated that SCD affects 90,000 to 100,000 people within The United States,
mainly Blacks or African Americans.
- The disease occurs among about 1 of each 500 Black or African American births and
about 1 out of each 36,000 Hispanic American births.
- SCD affects innumerable people throughout the globe and is
particularly common among those whose ancestors come from subSaharan Africa;
regions within the occident (South America,
the Caribbean, and Central America); Saudi Arabia; India; and
Mediterranean countries like Turkey, Greece, and Italy.

5. What Health Problems Does Sickle Cell Disease Cause?

- The sickle cells that contain mostly HbS are harder and less flexible than normal red
blood cells. So, they don’t move easily through small blood vessels and can get stuck and
clog the blood flow. This can happen quite suddenly, causing various symptoms which
are called a sickle cell crisis. Repeated blockages may result in complications occurring.
- During the first 3-6 months, a child may not show signs of having SCD, because there is
a high level (about 90%) of baby HbF and a very low level of sickle HbS (about 5-10%).
Over the first year, the HbF level is lesser as the child starts producing more HbS.
- Some children continue to make higher levels of HbF even into adulthood

pg. 3
 *Some of the most common complications of SCD*

 Anemia:
- Anemia comes from an Ancient Greek word meaning lack of blood. It is characterized by
either a lower number of red blood cells(RBCs) or a lower quantity of hemoglobin in the
RBCs than normal. In the SCD case, there is a mutation in the HbS, which leads to their
polymerization, causing the RBCs to sickle.
- These RBCs have a shorter lifespan than normal RBCs.This is known as hemolytic anemia,
which leads to vasculopathy(problems with the circulatory system), including systemic
and pulmonary hypertension (high blood pressure)problems with the function of the cells
that line blood vessels (endothelial cells) and the smooth muscle surrounding the vessels,
such as changes in their proliferation (division and replication)
- When a child is making more HbS, their red blood cells will not live in the circulation as long
as cells that contain the usual HbA. The body tries to keep up by making more red blood cells
but it usually cannot be completely maintained and the child becomes anemic.
- This type of anemia is understood as hemolytic anemia and is not the same as the sort of
anemia caused by a lack of iron.
 Jaundice:
- When the red blood cells come to the end of their life, they are
broken down in the body. One of the substances that are produced is
a yellow pigment called bilirubin. The liver clears the bilirubin from
the body, if there is a lot of bilirubin the liver may not be able to clear
it all away and the yellow pigment may appear in the eyes, a
condition known as jaundice.
 Enlarged spleen:
- The spleen may continue to be enlarged for some time but then
reduces in size and may stop working altogether.
 Pain Episode or Crisis:
They occur when sickle cells block small blood vessels in bones, which causes pain. The pain
usually occurs in bones and joints. The pain can vary from mild to severe, causing chronic or
episodic pain that can start suddenly.
- A Common sign of SCD may be painful swelling of the fingers and hands or toes and feet.
This is known as dactylitis(hand-foot syndrome) and may occur from about 6 months of age.
- Swelling in the hands and feet, often along with a fever, is caused by the sickle cells getting
stuck in the blood vessels and blocking the blood from flowing freely through the hands and
feet.
- Episodes of tummy (abdominal) pain can occur if sickle cells block blood vessels in your
abdomen.
 Physical growth and development:
- It is usual for SCD kids to be thinner and shorter than normal kids; however, they
generally grow at a steady rate.
- They tend to go through puberty at an older age than usual and this means that they also
go on growing for a little bit longer but eventually reach their normal adult height.
Bedwetting is also known as nocturnal enuresis.
 Infection:
- People with SCD, especially infants and children, are more likely to experience harmful
infections such as flu, meningitis, and hepatitis.

pg. 4
  Acute Chest Syndrome (ACS):

- Blockage of the flow of

blood to the lungs can cause
acute chest syndrome. ACS
is similar to pneumonia;
symptoms include chest
pain, coughing, difficulty
breathing, and fever. ACS
can start a few days after a
painful sickle crisis.
- It is most common in
women who are pregnant or
who have recently had a
baby.
 Stroke:
- Sickle cells can
clog blood flow to the brain and cause a stroke. A stroke can result in lifelong
disabilities and learning problems.
- Extensive sickle-cell damage to the brain vessels may result in Moya-Moya
disease what is named for the puff of smoke collateral vessels that bypass
blocked arteries.
 VTE (VENOUS THROMBOEMBOLISM):
- Sickling of red blood cells can increase the risk of
developing blood clots in the deep veins (deep-vein
thrombosis, DVT), or the lungs (pulmonary
embolism, PE).
- DVT and PE can cause serious illness, disability,
and, in some cases, death.

6. Diagnosis Of Sickle Cell Disease:

- SCD is diagnosed with a simple blood test. It most
often is found at birth during routine newborn
screening tests at the hospital. In addition, SCD can be diagnosed before birth.
- These tests vary from being high to minimally invasive, but all are accurate procedures in
determining the presence of the SCT or disease in a patient.
- The blood sample is analyzed to see what type of hemoglobin is present in the blood
(using a test called hemoglobin electrophoresis or other methods).
- It can also be identified with a blood smear looking for sickle cells.

pg. 5
 - Early

detection is important because it can help reduce the likelihood of sickle cell anemia
patients suffering from bacterial infections, pneumonia, and acute splenic sequestration
crisis, all of which have a high mortality rate in the first 3 years of infant life.

7. Treatment For Sickle Cell Disease (SCD)?

- In many cases, SCD cannot be cured, so lifelong treatment and monitoring are needed.
Treatments are available that can prevent complications and lengthen the lives of those who
have this condition. These treatment options can be different for each person depending on
the symptoms and severity.
 The factors that cause red blood cells to sickle which are hypoxia dehydration or acidosis can be
improved with oxygen and fluids which are the mainstays of treatment.
 Opioids are usually used to manage pain and antibiotics are used to treat any underlying bacterial
infections causing ACS.
 Blood transfusions are also used but the risk of multiple transfusions include iron overload and
the risk of developing new antibodies against future blood transfusions.
 children with sickle cell typically get prophylaxis with penicillin and an additional polysaccharide
vaccine against streptococcus pneumonia to help prevent sepsis and meningitis with encapsulated
bacteria.
 Hydroxyurea is a medicine that can decrease several complications of SCD. This treatment is
very safe when given by medical specialists experienced in caring for patients with SCD.
Hydroxyurea works by increasing the
amount of γ-globin which results in
more fetal hemoglobin or HbF. Fetal
hemoglobin is made up of two α and two
γ- globin chains so it does not include
the mutated β-globins. Since it cannot
polymerize it gets in the way of HBS
polymers being made and prevents
sickling; However, the side effects of
taking hydroxyurea during pregnancy or
for a long time are not completely
known.  

pg. 6
  The Food and Drug Administration has also approved a new medicine to reduce the number of
sickle cell crises in adults and children older than age five; it is called Endari (L-glutamine oral
powder).
 Another treatment, which can cure SCD, is a stem cell transplant (also called a bone marrow
transplant); this procedure infuses healthy cells, called stem cells, into the body to replace
damaged or diseased bone marrow (bone marrow is the center of the bone where blood cells are
made). Although transplants of bone marrow or blood from healthy donors are increasingly being
used to successfully cure SCD, they require a matched donor (a person with similar, compatible
bone marrow), and transplants can sometimes cause severe side effects, including occasional life-
threatening illness or death. People with SCD and their families should ask their doctors about the
benefits and risks of each treatment option. Research also shows that babies and children with
SCD can also benefit from hydroxyurea therapy.
 There are simple steps that people with SCD can take to help prevent and reduce the number of
pain crises. Most pain related to SCD can be treated with over-the-counter pain medications such
as ibuprofen and aspirin. Some people who have severe pain are given opioid (i.e. morphine)
medications daily, along with additional pain medication. Some people may be admitted to the
hospital for intense treatment.

 Blood transfusions are used to treat severe anemia. A sudden worsening of anemia resulting from
infection or enlargement of the spleen is a common reason for a transfusion. Multiple blood
transfusions, however, might cause health problems because of the iron content of the blood. Iron
overload, called hemosiderosis, can damage the liver, heart, pancreas, and other organs, leading
to diseases such as diabetes mellitus. Iron chelation therapy should be started in patients with
SCD receiving regular blood transfusions to reduce excess iron levels.

 Infections are treated with antibiotic medicines and sometimes blood transfusions. At the first
sign of an infection, such as a fever, it is important to see a doctor right away as this may
represent a medical emergency for people with SCD. Early treatment of infection can help
prevent problems.

 Stroke can be identified using a special type of exam called, transcranial Doppler ultrasound
(TCD). If the child is found to have an abnormal TCD, a doctor might recommend frequent blood
transfusions to help prevent a stroke. People who have frequent blood transfusions must be
watched closely because there are serious side effects.

pg. 7
 References:

Adejumo, O. E., Owa-Agbanah, I. S.,

Kolapo, A. L., Ayoola,
M.D., 2011. Phytochemical and
antisickling activities of
Entandrophragma utile, Chenopodium
ambrosioides and
Petiveria alliacea. Journal of
Medicinal Plants Research
Vol. 5(9), pp.1531-153
Adejumo, O. E., Owa-Agbanah, I. S.,
Kolapo, A. L., Ayoola,
M.D., 2011. Phytochemical and
antisickling activities of

pg. 8
Entandrophragma utile, Chenopodium
ambrosioides and
Petiveria alliacea. Journal of
Medicinal Plants Research
Vol. 5(9), pp.1531-153
Adejumo, O. E., Owa-Agbanah, I. S.,
Kolapo, A. L., Ayoola,
M.D., 2011. Phytochemical and
antisickling activities of
Entandrophragma utile, Chenopodium
ambrosioides and
Petiveria alliacea. Journal of
Medicinal Plants Research
Vol. 5(9), pp.1531-153
Adejumo, O. E., Owa-Agbanah, I. S.,
Kolapo, A. L., Ayoola,
M.D., 2011. Phytochemical and
antisickling activities of

pg. 9
Entandrophragma utile, Chenopodium
ambrosioides and
Petiveria alliacea. Journal of
Medicinal Plants Research
Vol. 5(9), pp.1531-153
Adejumo, O. E., Owa-Agbanah, I. S.,
Kolapo, A. L., Ayoola,
M.D., 2011. Phytochemical and
antisickling activities of
Entandrophragma utile, Chenopodium
ambrosioides and
Petiveria alliacea. Journal of
Medicinal Plants Research
Vol. 5(9), pp.1531-153
Adejumo, O. E., Owa-Agbanah, I. S.,
Kolapo, A. L., Ayoola,
M.D., 2011. Phytochemical and
antisickling activities of

pg. 10
Entandrophragma utile, Chenopodium
ambrosioides and
Petiveria alliacea. Journal of
Medicinal Plants Research
Vol. 5(9), pp.1531-153
Adejumo, O. E., Owa-Agbanah, I. S., Kolapo, A. L., Ayoola,M.D., 2011. Phytochemical and antisickling activities ofEntandrophragma utile, Chenopodium
ambrosioides andPetiveria alliacea. Journal of Medicinal Plants ResearchVol. 5(9), pp.1531-153

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