SICKLE CELL ANAEMIA

A BIOLOGY PROJECT REPORT

Submitted By

AATHAVAN.P, CLASS XI

SRIMATHI SUNDARAVALLI MEMORIAL SCHOOL

CHENNAI

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 ACKNOWLEDGMEMTS

The success and final outcome of this project required a lot of guidance and assistance from
many people and I am extremely privileged to thank the biology teacher for providing me an
opportunity to do the project work and giving me all the support and guidance, which made
me the complete the project appropriately. I am also extremely thankful to all my friends for
providing me support and guidance.

Aathavan.P
Class XI

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ABSTRACT

Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's
parents. The most common type is known as sickle cell anaemia (SCA). It results in an
abnormality in the oxygen-carrying protein haemoglobin found in red blood cells. This leads
to a rigid, sickle-like shape under certain circumstances. Problems in sickle cell disease
typically begin around 5 to 6 months of age. A number of health problems may develop, such
as attacks of pain (known as a sickle cell crisis), anaemia, swelling in the hands and
feet, bacterial infections and stroke. Long-term pain may develop as people get older. The
average life expectancy in the developed world is 40 to 60 years.

Sickle cell disease occurs when a person inherits two abnormal copies of the β-globin
gene (HBB) that makes haemoglobin, one from each parent. This gene occurs in chromosome
11. Several subtypes exist, depending on the exact mutation in each haemoglobin gene. An
attack can be set off by temperature changes, stress, dehydration, and high altitude. A person
with a single abnormal copy does not usually have symptoms and is said to have sickle cell
trait. Such people are also referred to as carriers. Diagnosis is by a blood test, and some
countries test all babies at birth for the disease. Diagnosis is also possible during pregnancy.

The care of people with sickle cell disease may include infection prevention
with vaccination and antibiotics, high fluid intake, folic acid supplementation, and pain
medication Other measures may include blood transfusion and the
medication hydroxycarbamide (hydroxyurea). A small percentage of people can be cured by
a transplant of bone marrow cells.

As of 2015, about 4.4 million people have sickle cell disease, while an additional 43 million
have sickle cell trait. About 80% of sickle cell disease cases are believed to occur in Sub-
Saharan Africa It also occurs relatively frequently in parts of India, the Arabian Peninsula,
and among people of African origin living in other parts of the world. In 2015, it resulted in
about 114,800 deaths.

This topic was interesting and I was curious of why a small change in haemoglobin could
result in a disease. So, out of curiosity, I chose this topic for my project.

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Table of contents

S.No. Content Page No.

1 Introduction 5

2 History of Sickle Cell 6

3 View into Haemoglobin 9

4 Genetics 11

5 Inheritance 12

6 Mechanism 14

7 Symptoms 15

8 Complication 17

9 Diagnosis 18

10 Treatment 20

11 Conclusion 22

12 Appendix 24

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 Introduction

Sickle Cell Anaemia

• It is an inherited form of anaemia – a condition in which there aren’t enough healthy

red blood cells (RBCs) to carry adequate oxygen throughout the body.
• Normally, your red blood cells are flexible and round, moving easily through your
blood vessels.
• In sickle cell anaemia, the red blood cells can get stuck in small blood vessels, which
can slow or block blood flow and oxygen to parts of the body.
• In simple terms, we can say that Sickle Cell Anaemia is a genetic disorder that affects
Erythrocytes causing them to become sickle or crescent shaped.
• The effects of this condition due to an abnormality of the haemoglobin molecules
found in erythrocytes.

This is the difference in the shape of a normal RBC and a Sickle

Cell

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 History Of Sickle Cells

• In 1904, Walter Clement Noel travelled 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 observe 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 anaemia”.
• 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 practise in St. Georges, the
capital city, until he died at the age of 32 from the acute chest syndrome.

1917-Genetic basis for SCD was given by Dr V. Emmel.

• The third cases of Sickle Cell were described in 1915 by Cook and Meyer in a 21-
year-old woman.

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 • 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 anaemia.
• 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 Anaemia

• Dr Mason, who observed the fourth reported case of Sickle cell, was also the first to
call the disease “Sickle Cell Anaemia” 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.

Dr V.R Mason- The man behind the name “Sickle Cell anaemia”

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 Erythrocytes

Properties of Erythrocytes

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 View into the Haemoglobin

➢ The oxygen-carrying pigment and predominant protein in the red blood cells.
➢ Haemoglobin forms an unstable, reversible bond with oxygen.
➢ Oxyhaemoglobin: Oxygenated Haemoglobin (Colour: Bright Red).
➢ Deoxyhaemoglobin: Reduced Haemoglobin (Colour: Purple-Blue)
➢ Each haemoglobin molecule is made up of four haeme groups surrounding a
globin group.
➢ Haeme contains iron and gives a red colour to the molecule.
➢ Globin consists of two linked pairs of polypeptide chains.

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10
 Genetics Of Sickle Cell Anaemia

➢ The change in cell structure arises from a change in structure of the haemoglobin.
➢ A single change in an amino acid causes haemoglobin to aggregate.

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 Inheritance of Sickle Cell Disease

• If one parent has sickle cell trait (HbAS) and the other does not carry the sickle
haemoglobin at all (HbAA) then none of the children will have sickle cell anaemia.
• 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.
• 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 anaemia.
• 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.
• If one parent has sickle cell trait (HbAS) and the other has sickle cell anaemia (HbSS)
there is a one in two (50%) chance that any given child will get sickle cell trait and one
in two (50%) chance that any given child will get sickle cell anaemia.
• No children will be completely unaffected.
• If one parent has sickle cell anaemia (HbSS) and the other is completely unaffected
(HbAA) then all the children will have sickle cell trait.
• None will have sickle cell anaemia.
• The parent who has sickle cell anaemia (HbSS) can only pass the sickle haemoglobin
gene to each of their children.

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Inheritance of Sickle Cell Anaemia

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 Mechanism

• When sickle haemoglobin (HbS) gives up its oxygen to the tissues, HbS sticks
together.
➢ Forms long rods from inside RBC
➢ RBC becomes 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 Anaemia

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 Symptoms

They vary from person to person and change over time, they 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 (anaemia).
Without enough red blood cells, your body can’t get the oxygen it needs to feel energized,
creating fatique.

•
• Episodes of pain. Periodic episodes of pain, called crisises, are a major symptom of
sickle cell anaemia.
• 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
only have a few pain episodes. Others have a dozen or more crisises a year. If a crisis is
severe enough, you might need to be hospitalized. Some adolescents and adults with
sickle cell anaemia have chronic pain, which can result from bone and joint damage,
ulcers and other causes.
• 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 anaemia vaccinations and antibiotics to prevent potentially life-
threatening infections such as pneumonia.

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• Delayed growth. Red blood cells provide your body with the oxygen and nutrients that
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.

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 Complications

Sickle cell anaemia 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. A stroke can be fatal.
• Acute chest syndrome. This life-threatening complication causes chest pain, fever and
difficulty in breathing. Acute chest syndrome can be caused by a lung infection or by
sickle cell blocking blood vessels in your lungs. It might require emergency medical
treatment with antibiotics and other treatments.
• Pulmanory hypertension. People with sickle cell anaemia 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.
• Organ damage. Sickle cells that block flow through blood vessels immediately deprive
the affected organ of blood and oxygen. In sickle cell anaemia, 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 possesses visual images (retina) and lead to
blindness.
• Leg ulcers. Sickle cell anaemia can cause open sores, called ulcers, on your cells.
• Gallstones. The breakdown of red blood cells produces a substance called bilirubin. A
high level of bilirubin in your body can lead to gallstones.

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 Diagnosis
• A blood test can check for haemoglobin S - the defective for haemoglobin that
underlies sickle cell anaemia. In the United States, this blood test is part of routine
new-born 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 genes are present.
• Check for a low red blood cell count (anaemia) will be done.

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 Genetic Counselling

Two tests can be used to help expectant parents find out if their child is unaffected.

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 foetus have the
same DNA). Under local anaesthesia, a thin needle is inserted through the
woman’s abdomen and into the womb. About 20 millilitres of fluid (roughly 4
teaspoons) is withdrawn and sent to lab for evaluation. Test results often take 1-2
weeks.

2. Chronic 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 foetus, 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 charges identified in an affected family member. Results are usually
available within 2 weeks.

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 Treatment

• Treatment is usually aimed at avoiding crises, relieving symptoms and preventing

complications. Babies and children aged 2 and younger with sickle cell anaemia
should make frequent visits to a doctor.
• Children older than 2 and adults with sickle cell anaemia should see a doctor at least
once a year, according to the Centre 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.

Assessing stroke risk

• Using a special ultrasound machine (transcranial), doctors can learn which

children have a higher risk of stroke. The painless test, which uses sound waves to
bmeasure 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 anaemia.

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 anaemia.
• Blood transfusions increase the number of normal red blood cells in circulation,
helping to relieve anaemia. In children with sickle cell anaemia at high risk of stroke,

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 regular blood transfusions can decrease the risk. Transfusions can also be used to treat
other complications of sickle cell anaemia, or they can be given to prevent
complications.
• Blood transfusions carry some risk, including infection and excess iron build-up 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.

• Nitric oxide. People with sickle cell anaemia 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.

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 Conclusion
• Sickle cell disease is a global health problem.
• It can result in distressing acute and chronic symptoms and can be life-threatening.
• There is no cure, therefore nurses should understand the actions that can prevent or
relieve symptoms in order to meet the challenges of caring for patients with sickle cell
disease and helping them to minimise its effects on their lives.

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Reference
1.Wikipedia

2.https://www.slideshare.net/MohamedElasalyPTCKTP/sickle-cell-anemia-75934817

3.https://www.hematology.org/education/trainees/fellows/case-studies/sickle-cell-disease-
a-25-year-old-in-transition

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 Appendix

Case Study

A 25-year-old woman with a history of sickle cell disease (SCD) presents to the clinic for
follow-up after a hospitalization for a vaso-occlusive pain crisis complicated by influenza
A. She has a history of an acute ischemic stroke at age 5 years and has received monthly,
simple red cell transfusions since the stroke. Her last transfusion was approximately four
months prior. She is taking deferasirox 20 mg/kg daily but occasionally misses doses.

Laboratory results show the following:

Haemoglobin 7.5 g/dL

Haematocrit 24%
Leukocyte count 9,300/mm3
Platelet count 202,000/m3
Mean corpuscular volume 105 fL
Haemoglobin electrophoresis 92% HbS, 6% HbF, 2% HbA2
Aspartate aminotransferase 24 U/L
Alanine aminotransferase 45 U/L
Ferritin 1,300 ng/mL

Which of the following is the next best step in diagnosis

A. Restart scheduled red blood cell transfusions

B. Start prophylactic penicillin
C. Discontinue transfusions and start hydroxyurea
D. Order transcranial doppler ultrasonography (TCD) to assess risk of stroke
E. Increase dose of deferasirox to 25 mg/kg/day

Answer

A. Restart scheduled red blood cell transfusions

Explanation

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The incidence of primary stroke in children with SCD is 0.6 to 0.8 events per 100 patient-
years, with a cumulative incidence of 7.8 percent by age 14 years in the Jamaican cohort and
11 percent by age 20 years in the U.S. Cooperative Study of Sickle Cell Disease. Once stroke
has occurred, the incidence of recurrent (secondary) stroke ranges from 47 to 93 percent in
patients not started on regular transfusions. The Stroke Prevention Trial in SCD (STOP)
randomized 130 high-risk children with SCD to either transfusion therapy (to maintain HbS
30%) or observation. These high-risk children had an increased blood flow in the internal
carotid or middle cerebral artery by TCD. This study showed a 92 percent reduction in
incidence of first stroke in transfused high-risk patients. A follow-up study, STOP2,
randomly assigned 72 children whose TCD had normalized after 30 months of transfusion
therapy to either ongoing or discontinued transfusions. The study was closed early due to a
significant increase in abnormal TCD velocity and stroke risk for those who halted
transfusion therapy.

The multicenter phase III TWiTCH trial evaluated children with SCA and abnormal TCD
velocities without a history of stroke on chronic transfusions. Data showed that hydroxyurea
at maximal tolerated dose was noninferior to chronic transfusions for maintaining TCD
velocities as primary stroke prophylaxis (choice C). This patient has a history of ischemic
stroke, so the results of TWiTCH do not apply to her.

The Stroke with Transfusions Changing to Hydroxyurea (SWiTCH) study was designed as a
phase III multicenter trial to determine the efficacy of hydroxyurea/phlebotomy, compared
with transfusions/chelation for children with SCA, stroke, and iron overload in secondary
stroke prophylaxis. The primary endpoint was a composite of noninferiority for stroke
prevention and superiority for reduction of liver iron content. The trial was terminated at the
first scheduled interim analysis for futility for the composite endpoint, which required
superiority of phlebotomy over iron chelation for reducing excess iron stores. The incidence
of stroke on the hydroxyurea plus phlebotomy arm was higher (7 of 67 patients; 10.4%) than
in the transfusion plus chelation arm (1 of 66 patients; 1.5%). These results, though not
powered for inferiority, showed a trend towars increased stroke risk with transition to
hydroxyurea. In patients with prior stroke, cessation of transfusion therapy is currently not
recommended.

Whether chronic transfusion therapy can be stopped after a longer period of transfusions in a
patient with a prior stroke remains unclear even though risk of recurrent stroke remains high

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in adolescence and young adulthood. In patients older than 16 years, TCD velocity criteria to
determine stroke risk is not reliable (choice D).

In the Prophylaxis with Oral Penicillin in Children with Sickle Cell Anemia trial, children
with SCA were randomly assigned to receive oral prophylactic penicillin or placebo PROPS
1986). The trial ended eight months early after the occurrence of 15 cases of pneumococcal
sepsis, 13 in the placebo group and two in the penicillin group, showing an 84 percent
reduction in pneumococcal sepsis with penicillin prophylaxis. The follow-up study, PROPS
II, did not show an increased risk in pneumococcal infections with discontinuation of
prophylactic penicillin after age 5 years. Therefore, prophylactic penicillin is not
recommended in adults with SCA (choice B).

The trajectory of ferritin in this patient has not been established and an increase in oral iron
chelation is not indicated at this time.

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