A detailed information on sickle cell Anemia

1. Sicklecellanaemia
Aakifah Amreen H.E
18LS301001
3rd sem MSc (BT)

2. Content
Introduction
Frequency
Inheritance pattern
Genetics
Mechanism of sickling
Signs and symptoms
Complications
Diagnosis
Treatment
References

3. Introduction
• Sickle cell anemia, or sickle cell disease (SCD), is a genetic
disease of the red blood cells (RBCs).
• A condition in which there aren’t enough healthy red blood
cells to carry adequate oxygen throughout body.
• The effect is due to an abnormality of the hemoglobin
molecules in blood
• Sickle cell disease is a serious and lifelong health condition,
although treatment can help manage many of the symptoms.

4. Continued……..
• Normally, RBCs are shaped like discs, which gives them the
flexibility to travel through even the smallest blood vessels.
• However, with this disease, the RBCs have an abnormal crescent
shape resembling a sickle.
• This makes them sticky and rigid and prone to getting trapped in
small vessels, which blocks blood from reaching different parts of
the body.
• This can cause pain and tissue damage.

5. Frequency
• Sickle cell disease affects millions of people worldwide.
• It is most common among people whose ancestors come from
Africa; Mediterranean countries such as Greece, Turkey, and
Italy; the Arabian Peninsula; India.
• Sickle cell disease is the most common inherited blood
disorder in the United States, affecting 70,000 to 80,000
Americans.
• The disease is estimated to occur in 1 in 500 African
Americans and 1 in 1,000 to 1,400 Hispanic Americans.

6. Inheritance pattern
• This condition is inherited in Autosomal reccesive condition ,
which means both copies of the gene in each cell have
mutations.
• The parents of an individual with an autosomal recessive
condition each carry one copy of the mutated gene, but they
typically do not show signs and symptoms of the condition.

8. Genetics
• Sickle cell disease is a hereditary hemoglobinopathy resulting
from inheritance of a mutant version of the β-globin gene (βA)
on chromosome 11.
• This gene codes for assembly of the β-globin chains of the
protein hemoglobin A.
• The mutant β-allele (βS) codes for the production of the
variant hemoglobin, hemoglobin S.
• The heterozygous carrier state is known as sickle cell trait
(SCT).
• The sickle cell gene mutation is a point mutation in the sixth
codon of exon 1 in the βA gene

9. • This gene is located on the short arm of Chromosome 11, and it
controls the production of the protein hemoglobin.
• The HBB gene contains 1,605 nucleotide base pairs, and the
hemoglobin gene is a sequence of 535 amino acids.
• A change in one nucleotide causes a single amino acid in the
protein to change: glutamic acid is replaced with lysine. This
causes the sickle cell trait
• Causing hemoglobin to aggregate.

10. • The change in cell structure arises from a change in the
structure of hemoglobin.

12. Mechanism of sickling of cell
• Hb has the physical properties of
forming polymers under deoxy
conditions.
• It also exhibits changes in solubility
and molecular stability.
• When sickle 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

14. Signs and 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.
• 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.

15. •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.
•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.

16. •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.
•Painful swelling of hands and
feet: The swelling is caused by
sickle-shaped red blood cells
blocking blood flow to the hands
and feet.

17. Complications
• 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.
• 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 lungs.
• 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.

18. • Organ damage: Sickle cells that block blood flow through
blood vessels immediately deprive the affected organ of blood
and oxygen. Organ damage can be fatal.
• Blindness: Sickle cells can block tiny blood vessels that
supply eyes. Over time, this can damage the portion of the eye
that processes visual images (retina) and lead to blindness.
• Gallstones: The breakdown of red blood cells produces a
substance called bilirubin. A high level of bilirubin in body
can lead to gallstones.

19. Diagnosis
Sickle cell disease and the presence of the sickle cell trait can be
diagnosed with blood tests or genetic tests.
• Sickle cell can be diagnosed at any age, but testing of
newborns is preferred, so that treatment can start as early as
possible.
• The disease can be diagnosed before birth by testing amniotic
fluid or placental tissue.
• Parents can be tested for the trait using the same blood tests in
order to determine if they are carriers.

20. Molecular diagnosis
• Hemoglobin electrophoresis-
Hb electrophoresis is always
needed to confirm the diagnosis
of sickle cell disease. It
measures the different types of
hemoglobin in the blood.
The substitution of the nonpolar
Valine for the charged Glutamic
acid results in decreased
mobility of the HbS in the
electric field as compared to
HbA. This altered mobility is
due to the presence of less
negative charge on the two β –
globin chains

21. Laboratory diagnosis
• A complete blood cell count usually reveals an increased
reticulocytes count (5– 15%)
• Total Leukocyte count (12,000– 20,000/mm3), upper
limit of normal or greater.
• Differential Leukocyte count- normal (or predominance
of neutrophils
• Mean corpuscular volume (MCV) normal (unless
thalassemic hemoglobin is present),
• Hb- mild to moderate anemia (5–9g/dL)
• Platelet count- normal to increased

22. • Blood smear
A diagnosis of sickle cell disease can be suspected by
examination of the peripheral blood film and that shows the
presence of target cells, poikilocytes, hypochromasia, sickle red
cells, nucleated RBCs
• Sickle solubility test
A mixture of hemoglobin S (Hb S) in a reducing solution
(such as sodium dithionite) gives a turbid appearance, whereas
normal Hb gives a clear solution
• HPLC-The diagnosis is confirmed by high- pressure liquid
chromatography (HPLC)

23. Treatment
• It 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.

24. • Bone marrow(stem cell) transplantation:
Currently, the only treatment that offers a potential cure for
sickle cell anemia is stem cell transplantation . This aims to
replace the sorce of red blood cells, the stem cells in the
bone marrow, with healthy stem cells from a matching
donor. This treatment is not available to everyone because
it can be very difficult to find a suitable donor.
Provide a definitive cure of SCD but with higher rate of
morbidity & mortality
A donor must be HLA- identical sibling to the recipient
 Pre-transplantation conditioning regimin includes:
busulfan or cyclophosphamide with or without
antithymocyte globulin.
Source of stem cells are: peripheral blood, bone marrow,
cord blood of a new born.
 The transplanted stem cells are administered
intravenously to the recipient to be engrafted in the
hemopoietic tissue space.

25. • There are several approved medications to
improve the symptoms of sickle cell anemia.
These include hydroxyeurea and Endari
(Lglutamine )
• Patients may also benefit from a transfusion of
healthy red blood cells, especially if they are at
high risk of complications such as a stroke.
• As pain is a common and debilitating symptom in
sickle cell anemia patients, their clinicians may
recommend painkillers such as acetaminophen or
non-steroidal anti-inflammatory drugs (NSAIDs),
such as ibuprofen and diclofenac. Opioids such as
codeine or morphine may also be prescribed for
more severe or chronic pain.
• Children may be prescribed daily penicillin from
as young as 2 months to prevent infections. This is
called penicillin prophylaxis and should be
complemented by vaccinations and antibiotics in
case of infection.

26. 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 considering ways to deliver a
functioning copy of the HBB gene to the patient’s
cells, and many clinical trials are ongoing or have
been completed to investigate this.
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.

27. • There are other experimental therapies that aim to more
effectively treat the symptoms of the disease.
• Voxelotor(GBT440), by Global Blood Therapeutics, targets
the underlying cause of sickle cell anemia, the abnormal
hemoglobin. It aims to prevent hemoglobin from sticking
together, which should allow the red blood cells to maintain a
partially normal and flexible shape.
• Some experimental therapies are aimed at finding ways to
improve blood flow and reduce the numbers of red blood cells
that get trapped inside the blood vessels.

28. Reference
• https://www.mayoclinic.org/diseases-conditions/sickle-cell-
anemia/symptoms-causes/syc-20355876
• https://ghr.nlm.nih.gov/condition/sickle-cell-disease#genes
• https://www.slideshare.net/MohamedElasalyPTCKTP/sickle-
cell-anemia-75934817
• AN OVERVIEW ON SICKLE CELL DISEASE PROFILE
KAUR M1, DANGI CBS1 & SINGH M2 1
Asian Journal of Pharmaceutical and Clinical Research
Vol 6, Suppl 1, 2013, ISSN - 0974-2441
https://www.researchgate.net/publication/263655859_An
_overview_on_Sickle_Cell_Disease_Profile/link/0a85e53b7b6b6
eeb51000000/download