This is to certify that Gunjan Bhatia, Nandini Agrawal,

Khushi Saluja and Alisha Syed have completed their project

report successfully.

It is the record of original bonafide work carried out by them

under our guidance. They worked sincerely and have given a
satisfactory account of it in this project.

DATE: 26/10/2015

TEACHER INCHARGES:

Mrs. Pratibha Nair

Ms. Shweta Parashar

Mr. Shyam Agrawal

(PRINCIPAL)

DECLARATION
We Gunjan Bhatia, Nandini Agrawal, Khushi Saluja and
Alisha Syed, of Queens’ College, Indore solemnly declare that
the project entitled “SICKLED IS NO MORE CRIPPLED” is
the result of our own efforts under the guidance of our teachers.

DATE: 26/10/2014

NAMES: SIGNATURE

GUNJAN BHATIA XI “B”

NANDINI AGRAWAL X “B”
KHUSHI SALUJA IX “D”
ALISHA SYED IX “C”

ACKNOWLEDGEMENT
We Gunjan Bhatia, Nandini Agrawal, Khushi Saluja and
Alisha Syed avail this opportunity to express our gratitude
towards respected Principal Sir, Mr. Shyam Agrawal for giving
us the valuable guidance and facilities to complete this work
successfully.

We are indebted and thankful to Madam Pratibha Nair and

Madam Shweta Parashar, our teachers under whose able and
purposeful guidance we could perform this project.
Cells in tissues need a steady supply of oxygen to work well. Normally,
haemoglobin in red blood cells takes up oxygen in the lungs and carries it to all the
tissues of the body. Red blood cells that contain normal haemoglobin are disc
shaped. This shape allows the cells to be flexible so that they can move through
large and small blood vessels to deliver oxygen. Sickle haemoglobin is not like
normal haemoglobin. It can form stiff rods within the red cell, changing it into a
crescent, or sickle shape.
The term sickle cell disease (SCD) describes a group of inherited red blood cell
disorders. People with SCD have abnormal haemoglobin, called haemoglobin S or
sickle haemoglobin, in their red blood cells. (Haemoglobin is a iron containing
cytochrome pigment in red blood corpuscles that carries oxygen throughout the
body)
“Inherited” means that the disease is passed by genes from parents to their
children. SCD is not contagious.
People who have SCD, inherit two abnormal haemoglobin genes, one from each
parent. In all forms of SCD, at least one of the two abnormal genes causes a
person’s body to make haemoglobin S. When a person has two haemoglobin S
genes, Haemoglobin SS, the disease is called sickle cell anaemia. This is the most
common and often most severe kind of SCD.

Sickle cell trait or the carrier state for sickle cell anaemia occurs in high frequency
among people of African-American and/or Hispanic descent, but it can also occur
in people of all ethnicities. When properly conducted, testing for
hemoglobinopathies also detects the carrier state for sickle cell disease and other
hemoglobinopathies.

It is a hereditary disorder that affects more than 13 million people around the
world. More than 800 children are born with SCD every day in Africa, and more
than half of them die in childhood due to lack of diagnosis and early treatment. The
sickle cell gene causes the body to produce abnormal haemoglobin. In sickle cell
disease, the haemoglobin clumps together, which causes red blood cells to become
stiff and develop a C-shaped (“sickle”) form. These sickled red blood cells can
block blood vessels, reducing blood flow in many parts of the body. This process
results in tissue and organ damage

NORMAL RED CELLS AND SICKLE RED CELLS:

Figure A shows normal red blood cells flowing freely in a blood vessel. The inset
image shows a cross-section of a normal red blood cell with normal haemoglobin.
Figure B shows abnormal, sickled red blood cells blocking blood flow in a blood
vessel. The inset image shows a cross-section of a sickle cell with abnormal
(sickle) haemoglobin forming abnormal stiff rods.
 HAEMOGLOBIN AND IRON:

● Each red blood cell contains about 280 million hemoglobin molecules.
Hemoglobin is the most important component of red blood cells. It is composed of
protein (globulin) and a molecule (heme), which binds to iron.
● In the lungs, the heme component takes up oxygen and releases carbon dioxide.
The red blood cells carry the oxygen to the body's tissues, where the hemoglobin
releases the oxygen in exchange for carbon dioxide, and the cycle repeats. The
oxygen is essential for all cells in the body to function.
● Sickle cell disease reduces or denies adequate oxygen to many parts of the body.
This contributes to the severe pain experienced as a sickle cell crisis and both short-
and long-term organ damage.
 WHY DID WE CHOOSE THIS TOPIC?

The main purpose of this research is to develop a system that could measure the
complex rheological properties of sickle blood as it passes through small blood
vessels with decreasing oxygen levels. People of all age groups lose their lives due
to lack in early diagnostic procedures.
 ● FOREIGN COUNTRY:

The disease originated in at least 4 places in Africa and in the Indian/Saudi

Arabian subcontinent. It exists in all countries of Africa and in areas where
Africans have migrated.
It is most common in West and Central Africa where as many as 25% of the people
have sickle cell trait and 1-2% of all babies are born with a form of the disease. In
the United States with an estimated population of over 270 million, about 1,000
babies are born with sickle cell disease each year. Approximately 70,000 - 100,000
individuals in the United States have sickle cell disease and 3 million have sickle
cell trait. In contrast, Nigeria, with an estimated 1997 population of 90 million,
45,000-90,000 babies with sickle cell disease are born each year.
The transatlantic slave trade was largely responsible for introducing the sickle cell
gene into the Americas and the Caribbean. However, sickle cell disease had
already spread from Africa to Southern Europe by the time of the slave trade, so it
is present in Portuguese, Spaniards, French Corsicans, Sardinians, and Sicilians,
mainland Italians, Greeks, Turks and Cypriots. Sickle cell disease appears in most
of the near and Middle East countries including Lebanon, Israel, Saudi Arabia,
Kuwait and Yemen.
The condition has also been reported in India and Sri Lanka. Sickle cell disease is
an international health problem and truly a global challenge.

Sickle cell disease (SCD) affects millions of people throughout the world and is
particularly common among those whose ancestors came from sub-Saharan Africa;
Spanish-speaking regions in the Western Hemisphere (South America, the
Caribbean, and Central America); Saudi Arabia; India; and Mediterranean
countries such as Turkey, Greece, and Italy.
Sickle cell disease occurs more often among people from parts of the world where
malaria is or was common. It is believed that people who carry the sickle cell trait
are less likely to have severe forms of malaria.

IN THE UNITED STATES

The exact number of people living with SCD in the U.S. is unknown. However, the
CDC in collaboration with the National Institutes of Health and 7 states
(California, Florida, Georgia, North Carolina, New York, Michigan and
Pennsylvania) are coordinating the Registry and Surveillance System for
Hemoglobinopathies(RuSH) project to learn about the number of people living
with SCD to better understand how the disease impacts their health.

It is estimated that:

● SCD affects 90,000 to 100,000 Americans.

● SCD occurs among about 1 out of every 500 Black or African-American
births.
● SCD occurs among about 1 out of every 36,000 Hispanic-American births.
● SCT occurs among about 1 in 12 Blacks or African Americans.

MORTALITY
Sickle cell-related death among Black or African-American children younger than
4 years of age fell by 42% from 1999 through 2002. This drop coincided with the
introduction in 2000 of a vaccine that protects against invasive pneumococcal
disease.
RELATIVE TO THE RATE FOR THE PERIOD 1983 THROUGH 1986,
THE SCD MORTALITY RATE FOR THE PERIOD 1999 THROUGH 2002
DECREASED BY:
● 68% at age 0 through 3 years;
● 39% at age 4 through 9 years; and
● 24% at age 10 through 14 years.

MORTALITY AMONG CHILDREN WITH SICKLE CELL DISEASE:

Among the children with Hb SS disease, 1% died as a result of SCD-related causes
during the first 3 years of life.In California and Illinois, by the end of 1995, the
cumulative mortality rate was 1.5 per 100 Black or African-American children
with SCD. The equivalent cumulative mortality rate for all Black or African-
American infants born during this period in California and Illinois was 2.0 per 100
Black or African-American newborns.

ECONOMIC COSTS:
During 2005, medical expenditures for children with SCD averaged $11,702 for
children with Medicaid coverage and $14,772 for children with employer-
sponsored insurance. About 40% of both groups had at least one hospital stay.
SCD is a major public health concern. From 1989 through 1993, an average of
75,000 hospitalizations due to SCD occurred in the United States, costing
approximately $475 million.

THE CASE IN INDIA:

The state Lokayukta had directed the public health department to conduct primary
population survey to determine the prevalence of sickle cell disease. Though the
department did not conduct the survey, it helped a non-governmental organization
with a similar survey. The report says 10.5% of the tribal population,
approximately 9,45,000 persons, are affected by the disease in Maharashtra.

Sickle Cell Disease International Organization (SCDIO) conducted the survey in

states of Maharashtra, Gujarat, Orissa, Madhya Pradesh and Tamil Nadu. The
effort was aimed at creating awareness on sickle-cell anaemia and to seek
government support to list the disease in the National Rural Health Mission.
SCDIO wants to make India SCD free.

"SCDIO has started an advocacy to consider SCD as a priority disease, by

conducting meetings with the central government and state ministries of health and
family welfare. We also plan to start Caravan Project to screen the population for
SCD in some states with high prevalence, and thereafter in other states with the
help of government and non-government organizations," said Dr. Hariom Sharma,
Global Scientific Coordinator of SCDIO. Agencies like department of health and
family welfare of the central government and various states and Indian Council of
Medical Research were also involved in the survey, he added.

The report of the organization reveals that nearly 20 million children are born with
sickle-cell anaemia in India every year. With its present rate of spread, in another
25-40 years, over 1.5 crore children will suffer and die of sickle-cell disease, and
over 3 crore person will inherit the abnormal haemoglobin trait, says the report.

About the prevalence of the disease in Maharashtra, the report counts 10.5% of the
tribal population, approximately 9, 45,000 people, as affected by the disease.
While the overall incidence of the disease in the state is less than 0.1%, it is very
high among the tribal population groups from Nan durbar and Gadchiroli districts.
The overall prevalence among tribal populations is about 10% for carriers of the
disease and 0.5% for sufferers. The same tribal population groups residing in
neighbouring states of Gujarat, Madhya Pradesh and Andhra Pradesh have a
similar prevalence.
Sickle cell anemia is caused by a mutation in the gene that tells your body to make
hemoglobin — the red, iron-rich compound that gives blood its red color.
Hemoglobin allows red blood cells to carry oxygen from your lungs to all parts of
your body. In sickle cell anemia, the abnormal hemoglobin causes red blood cells
to become rigid, sticky and misshapen.

The sickle cell gene is passed from generation to generation in a pattern of

inheritance called autosomal recessive inheritance. This means that both the
mother and the father must pass on the defective form of the gene for a child to be
affected.
Abnormal hemoglobin, called hemoglobin S, causes sickle cell disease (SCD). The
problem in hemoglobin S is caused by a small defect in the gene that directs the
production of the beta globin part of hemoglobin. This small defect in the beta
globin gene causes a problem in the beta globin part of hemoglobin, changing the
way that hemoglobin works
HOW IS SICKLE CELL DISEASE INHERITED?

● When the hemoglobin S gene is inherited from only one parent and a normal
hemoglobin gene is inherited from the other, a person will have sickle cell trait.

● People with sickle cell trait are generally healthy. Only rarely do people with
sickle cell trait have complications similar to those seen in people with SCD.

● But people with sickle cell trait are carriers of a defective hemoglobin S gene.
So, they can pass it on when they have a child. If the child’s other parent also
has sickle cell trait or another abnormal hemoglobin gene (like thalassemia,
hemoglobin C, hemoglobin D, hemoglobin E), that child has a chance of having
SCD.

● If only one parent passes the sickle cell gene to the child, that child will have
the sickle cell trait. With one normal hemoglobin gene and one defective form
of the gene, people with the sickle cell trait make both normal hemoglobin and
sickle cell hemoglobin. Their blood may contain some sickle cells, but they
generally don't experience symptoms. However, they are carriers of the disease,
which means they can pass the defective gene on to their children.

The image shows how sickle hemoglobin genes are inherited. A person inherits
two hemoglobin genes—one from each parent. A normal gene will make normal
hemoglobin (A). A sickle hemoglobin gene will make abnormal hemoglobin (S).

In the image below, each parent has one hemoglobin A gene and one hemoglobin S
gene, and each of their children has:
 RISK OF INHERITANCE

People inherit a pair of genes that regulate hemoglobin, with one gene coming
from each parent. If two sickle genes are inherited, a person will have sickle cell
disease. If a one normal hemoglobin gene and one sickle cell gene are inherited, a
person will have sickle cell trait. People who have sickle cell trait are healthy and
do not develop themselves sickle cell disease, but they are “carriers” who can pass
the disease on to their children.

The risk of a child inheriting sickle cell disease or sickle cell trait is as follows:

● If both parents have sickle cell trait (each have one normal hemoglobin gene and
one sickle cell gene), the child has a 50% chance of inheriting sickle cell trait (one
 normal gene, one sickle cell gene), 25% chance of inheriting sickle cell disease
(two sickle cell genes), and 25% chance of not inheriting either the trait or the
disease (two normal genes).

● If one parent has sickle cell trait (one normal gene and one sickle cell gene) and the
other parent has two normal hemoglobin genes, the child has a 50% chance of
inheriting sickle cell trait (one normal gene and one sickle cell gene) and a 50% of
inheriting neither the trait nor the disease (two normal genes). The child is not at
risk of inheriting sickle cell disease.

● If one parent has sickle cell disease (two sickle cell genes) and the other parent has
sickle cell trait (one normal gene, one sickle cell gene), the child has a 50% chance
of inheriting sickle cell trait and a 50% chance of inheriting sickle cell disease.

● If one parent has sickle cell disease and the other parent has two normal
hemoglobin genes, the child has a 100% chance of inheriting sickle cell trait, but
not the disease.

● If both parents have sickle cell disease, the child has a 100% chance of inheriting
the disease.

TYPE OF MUTATION OBSERVED:

Type of mutation observed in SCD is substitution.
A substitution is a mutation that exchanges one base for another (i.e., a change in
a single "chemical letter" such as switching an A to a G). Such a substitution could:
● Change a codon to one that encodes a different amino acid and cause a small
change in the protein produced. For example, sickle cell anaemia is caused
by a substitution in the beta-haemoglobin gene, which alters a single amino
acid in the protein produced.
● Change a codon to one that encodes the same amino acid and causes no
change in the protein produced. These are called silent mutations.
● Change an amino-acid-coding codon to a single "stop" codon and cause an
incomplete protein. This can have serious effects since the incomplete
protein probably won't function.
EFFECTS OF MUTATION: SICKLE CELL ANEMIA
The mutations that cause sickle cell anemia have been extensively studied and
demonstrate how the effects of mutations can be traced from the DNA level up to
the level of the whole organism. Consider someone carrying only one copy of the
gene. She does not have the disease, but the gene that she carries still affects her,
her cells, and her proteins:

1. There are effects at the DNA level

2. There are effects at the protein level

Normal hemoglobin and hemoglobin in sickled red blood cells look
different; the mutation in the DNA slightly changes the shape of the
hemoglobin molecule, allowing it to clump together.
Signs and symptoms of sickle cell anemia often don't appear until an infant is
at least 4 months old and may include:

● ANEMIA: Sickle cells are fragile. They break apart easily and die, leaving you
without a good supply of red blood cells. Red blood cells usually live for about
120 days before they die and need to be replaced. But sickle cells die after an
average of less than 20 days. This results in a lasting shortage of red blood cells
(anemia). Without enough red blood cells in circulation, your body can't get the
oxygen it needs to feel energized. That's why anemia causes 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. The pain may vary in intensity and
can last for a few hours to a few weeks. Some people experience only a few
episodes of pain. Others experience a dozen or more crises a year. If a crisis is
severe enough, you may need to be hospitalized.

● HAND FOOT SYNDROME: Swollen hands and feet may be the first signs of
sickle cell anemia in babies. The swelling is caused by sickle-shaped red blood
cells blocking blood flow out of their hands and feet. Hand-foot syndrome,
 also called palmar-plantar erythrodysesthesia, is a side effect of some types of
chemotherapy. 

Hand-foot syndrome causes redness, swelling, and pain on the palms of

the hands and/or the soles of the feet.

● VISION PROBLEMS: Some people with sickle cell anemia experience 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.
● GENERAL SYMPTOMS IN CHILDREN: Pain is the most common
complaint. It can be acute and severe or chronic, usually from orthopedic
problems in the legs and low back. Other symptoms include:

● Fatigue and shortness of breath (signs of anemia)

● Irritability
● Jaundice (yellowish discoloration of the skin and eyes)

● ADDITIONAL SYMPTOMS IN ADOLESCENCE OR ADULTHOOD:

Symptoms of childhood continue in adolescence and adulthood. In addition,
patients may experience.

● DELAYED PUBERTY (IN YOUNG TEENAGERS)

● SEVERE JOINT PAIN

● PROGRESSIVE ANEMIA
● LEG SORES
● GUM DISEASE
 ● FREQUENT INFECTIONS: Sickle cells can damage your spleen, an organ
that fights infection. This may make 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.

THE SICKLE CELL DISEASE PROCESS

The symptoms and problems of sickle cell disease are a result of the hemoglobin S
(HbS) molecule:

● When the sickle hemoglobin molecule loses its oxygen, it forms rigid rods called
polymers that change the red blood cells into a sickle or crescent shape.
● These sickle-shaped cells stick to the walls and cannot squeeze through the
capillaries. Blood flow through tiny blood vessels becomes slowed or stopped in
many parts of the body. This deprives tissues and organs of oxygen.
● When this blood flow slows or stops suddenly in a certain part of the body, the
decrease in oxygen (hypoxia) can cause severe pain (the sickle cell crisis). Over
time, it leads to gradual destruction in organs and tissues throughout the body.
● The higher the concentration of sickle hemoglobin and the more acidic the
environment, the faster the sickle cell process.
● When blood cells dry out (dehydrate), the density of hemoglobin S within the cell
increases, thereby speeding the sickling process.
● Sickle cells also have a shorter life span (10 - 20 days) than that of normal red
blood cells (90 - 120 days). Every day the body produces new red blood cells to
replace old ones, but sickle cells become destroyed so fast that the body cannot
keep up. The red blood cell count drops, which results in anemia. This gives sickle
cell disease its more common name, sickle cell anemia.
 INTERVIEW:

1. DR.RAJKUMAR AGRAWAL:
2. DR.A SABARWAL:

We had an elaborated interview with both the specialized dr. who gave us
several information about sickle cell anaemia. According to them sickle cell
anaemia is a severe disease which is inherited from parents to offspring’s.
People at risk for inheriting the gene for sickle cell descend from people who
 are or were originally from Africa and parts of India and the Mediterranean.
Sickle cell disease changes normal, round red blood cells into cells that can be
shaped like crescent moons. Because of this disease many people are dying
worldwide. This disease needs to be diagnosed otherwise this may affect our
population very badly. They told us about unawareness of people regarding this
disease. They gave us several traditional method upon which this disease can be
taken care of. Not only this they both seemed very happy after looking our
enthusiasm towards this severe disease and the way are we trying to absolve it.

CASE STUDIES:

Here is a case study taken from worldwide about the people who are suffering
from SICKE CELL ANAEMIA and their experience which was shared by his
parents.
On the morning of admission, our patient, a 19-year-old African-American man
with sickle cell anaemia, felt himself to be in his usual state of health, although he
had just been discharged the previous day from a hospitalization for acute chest
syndrome.. However, at approximately 5:45 p.m., he noticed that he could not pull
up his trousers due to weakness in his left arm. As he walked out , he noted that he
was having difficulty walking because of weakness in his right and left leg. He
began experiencing ‘shocking’ pains on both sides of his neck, which were unlike
his usual pain, and also noted that he had an erection. These events transpired
rapidly, within about six minutes, at which point his family called Emergency
Medical Services (EMS) and our patient was transported to hospital.

On arrival at our hospital, he was alert and oriented and cranial nerves II to XII
were intact. He had flaccid paralysis of the bilateral upper extremities and the left
lower extremity.. The results of the rest of his physical examination were normal.

Relevant medical history included asthma, recurrent acute chest syndrome and
intermittent attempts at Hydroxyurea. He was treated for the three years with
exchange transfusions to maintain hemoglobin S < 30 percent; during this time he
did very well. At 10 days prior to presentation, he was hospitalized with an acute
chest syndrome.. He was treated with antibiotics and a transfusion. His discharge
hemoglobin was 6.6 and oxygen saturation 96 percent. He was without symptoms
at the time of discharge.

The results of peripheral blood and urine cultures were negative. A chest X-ray
showed patchy consolidation in the right upper lobe suspicious for pneumonia. The
results of computed tomography (CT) angiography of the head and neck were
unremarkable.

Later the initial MRI was read to also show swelling of the cord in the same area.
He was admitted to the neurologic intensive care unit where he received an
exchange transfusion with no significant improvement in his symptoms
andsubsequent hemoglobin electrophoresis. While in the intensive care unit (ICU)
he experienced episodes of hypotension that were initially managed with
vasopressors. His erythrocyte sedimentation rate (ESR) and C-reactive protein
(CRP) levels were both elevated, and proteins C and S were found to be low but
within the expected range for someone with sickle cell disease. He was anti-
coagulated with a heparin drip during his stay in the acute care facility, but this
was discontinued on discharge. A monthly exchange transfusion regimen was
instituted with the goal of keeping his haemoglobin S level. Currently, at 20
months post-spinal cord infarction, his condition is unchanged.

SURVEYS:

Here is a survey done by our queens. Our queens surveyed three people Palak
Dubey, Avantika Joshi and Sharad Agrawal who are been suffering through this
disease. They shared their experience with us.

Common conclusion:
Out of the three surveys that we conducted all the patients had problem in
managing their normal routines. No medicines are there to rectify the error.
They were thrilled to learn about the new painless method of early diagnosis of the
problem. They enquired about the application of this diagnostic chip in INDIA and
its availability.
Lack in early diagnosis can lead to severe ill effects on health and can lead to
following complications:

1)INFECTIONS: Late diagnosis may lead to increased risk of severe bacterial

infections due to loss of functioning spleen tissue. These infections are typically
caused by encapsulated organisms such as Streptococcus pneumonia and
hemophilic influenza.

2)STROKE: Stroke which can result from a progressive narrowing of blood

vessels prevents oxygen from reaching the brain. Cerebral infraction occurs in
children and cerebral hemorrhage in adults. A cerebral infarction is a type of
ischemic stroke resulting from a blockage in the blood vessels supplying blood to
the brain. It can be atherothrombotic or embolic. Stroke caused by cerebral
infarction should be distinguished from two other kinds of stroke: cerebral
hemorrhage and subarachnoid hemorrhage.

3)SILENT STROKE: It causes no immediate symptoms, but is associated with

damage to the brain. Silent stroke is probably five times as common as
symptomatic stroke. About 10–15% of children with SCD suffer strokes, with
silent strokes predominating in the younger patients.

4)CHOLELITHIASIS AND CHOLECYSTITIS: Lack in early diagnosis can

lead to Cholelithiasis which is a medical term used for Gall Stones which are
concretions that form in the biliary tract, usually in the Gall bladder. It can also
lead to Cholecystitis which is inflammation of the Gall Bladder.
5)VASCULAR NECROSIS: Complications like Avascular necrosis may arise.
Avascular necrosis is the death of bone tissues due to a lack of blood supply. This
is also referred to as Osteonecrosis as it can lead to tiny breaks in the bone and the
bone’s eventual death. Avascular necrosis of the hip and other major joints may
occur as a result of ischemia. Ischemia is a restriction in blood supply to the
tissues, causing a shortage of oxygen and glucose needed for cellular metabolism.

6)OSTEOMYELITIS: Osteomyelitis is the inflammation of bone or bone

marrow, usually due to infection. The most common cause of Osteolyelitis in SCD
is Salmonella.

7)PULMONARY HYPERTENSION: Pulmonary hypertension (PH) is an

increase of blood pressure in the pulmonary artery, pulmonary vein,
or pulmonary capillaries, together known as the lung vasculature, leading to
shortness of breath, dizziness, fainting, leg swelling, episodes of syncope,
decreased exercise tolerance, increased risk of heart failures and other
symptoms.21% of children and 30% of adults have evidence of pulmonary
hypertension when tested.
8)CHRONIC KIDNEY FAILURE: It occurs due to sickle-cell nephropathy
manifests itself with hypertension, protein loss in the urine, loss of red blood cells
in urine and worsened anemia. Sickle cell nephropathy is a type of nephropathy
(kidney disease) associated with sickle cell disease, it causes kidney complications
as a result of sickling of red blood cells in the small blood vessels.If it progresses
to end-stage renal failure, it carries a poor prognosis.

9)DURING PREGNANCY: A pregnant lady can suffer from the following

complications if she is suffering from Sickle cell disease :

a)intrauterine growth retardation : It refers to poor growth of a fetus

while in the mother's womb during pregnancy. The causes can be many, but most
often involve poor maternal nutrition or lack of adequate oxygen supply to the
fetus.

b)spontaneous abortion

c)pre-eclampsia: a condition in pregnancy characterized by high blood

pressure, sometimes with fluid retention and proteinuria.

10)EYE DAMAGE: In eyes, background retinopathy, proliferative retinopathy,

vitreous hemorrhages, and retinal detachments can result in blindness.
11)ACUTE CHEST SYNDROME (ACS): Acute chest syndrome occurs when
the lung tissues are deprived of oxygen during a crisis. It can be very painful,
dangerous, and even life threatening. It is a leading cause of illness among sickle
cell patients and is the most common condition at the time of death.

12)CHRONIC PAIN: Even in the absence of acute vaso-occlusive pain, many

patients have unreported chronic pain.
HEMOGLOBIN ELECTROPHORESIS:
Sickle-shaped red blood cells can be seen when a blood sample is examined under
a microscope. But sickle cell disease is diagnosed by a blood test called
hemoglobin electrophoresis, which measures the amount of the abnormal sickle
hemoglobin. The amount of sickle hemoglobin determines whether the person is a
carrier (sickle cell trait) or has sickle cell disease.

 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. The sample is
then sent to a laboratory, where it's screened for hemoglobin S.
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. People who have one gene — sickle cell trait — have a
fairly small percentage of hemoglobin S. People with two genes — sickle cell
anemia — have a much larger percentage of the defective hemoglobin.

ADDITIONAL TESTS:
To confirm any diagnosis, a sample of blood is examined under a microscope to
check for large numbers of sickle cells — a marker of the disease. If you or your
child has the disease, a blood test to check for anemia — a low red blood cell count
— will be done. And your doctor may suggest additional tests to check for possible
complications of the disease.
If you or your child carries the sickle cell gene, you may be referred to a genetic
counselor — an expert in genetic diseases.

TESTS TO DETECT SICKLE CELL GENES BEFORE BIRTH:

Sickle cell disease can be diagnosed in an unborn baby by sampling some of the
fluid surrounding the baby in the mother's womb (amniotic fluid) to look for the
sickle cell gene. If you or your partner has been diagnosed with sickle cell anemia
or sickle cell trait, ask your doctor about whether you should consider this
screening. 

TRANSCRANIAL DOPPLER (TCD) ULTRASONOGRAPHY:

● The Transcranial Doppler (TCD) and the more recent trans cranial color

Doppler (TCCD) are tests that measure the velocity of blood flow through
the brain’s blood vessels.
● This test can probably detect the sickle cell disease.
 ● The tests are often used in conjunction with other tests such
as MRI, MRA, carotid duplex ultrasound and CT scans.

MAGNETIC RESONANCE IMAGING (MRI)

● The use of follow-up magnetic resonance imaging (MRI) to detect small blockages
in blood vessels may help confirm high risk in patients identified by TCD
ultrasound.

ANGIOGRAPHY:

Some patients may need to undergo angiography, an invasive diagnostic technique

useful for detecting aneurysms. Angiography or arteriography is a medical
imaging technique used to visualize the inside, or lumen, of blood vessels and
organs of the body, with particular interest in the arteries, veins, and the heart
chambers.
Treatment goals for sickle cell disease aim to relieve pain, prevent infections, and
manage complications.

There is still no cure for sickle cell disease other than experimental transplantation
procedures, but treatments for complications of sickle cell have prolonged the lives
of many patients who are now living into adulthood.

BONE MARROW TRANSPLANTATION

Stem cell transplantation is a potential cure for sickle cell disease. Stem cells can

be found in bone marrow. Bone marrow is the substance in the center of your
bones that produces red blood cells. A person with sickle cell disease has bone
marrow that produces red blood cells with defective hemoglobin S. But if that bone
marrow is replaced with healthy bone marrow, a person's body may start to
produce normal hemoglobin.
Stem cell transplants require bone marrow from another person (donor). This is
called an allogeneic stem cell transplant.
Before the transplant, bone marrow stem cells are taken from someone who has
closely matching bone marrow, usually a healthy brother or sister. The child who
has sickle cell disease is then treated with drugs that destroy his or her bone
marrow cells. After that, the donated bone marrow stem cells are injected into a
vein.
After the process is complete, the donor's bone marrow begins to replace the
recipient's bone marrow. These new cells restore the immune system and make
normal red blood cells.
THE POSSIBLE RISKS OF TRANSPLANT:
● Infections – Chemotherapy lowers the white blood cells, which normally
fight and prevent infections. – This puts the patient at high risk for
infections, which can be caused by bacteria, fungi, or viruses. – Medicines
are given to fight these germs and prevent these infections. Infections that do
not respond to the treatment can lead to death in 5 to 10 percent of patients.
● Graft-versus-host disease (GVHD) –

This reaction occurs when the immune cells of the donor (graft cells) sense that
cells of the patient (host cells) are different and attack them. This can be a serious
side effect of transplant. – GVHD occurs in up to 10 percent of patients who
undergo matched related types of transplants. It can be higher in transplants using
other donors. – This condition can be acute (occurring less than 100 days after the
transplant) or chronic (occurring more than 100 days after transplant). – It may
cause damage to the skin, liver, and intestinal tract of the transplanted patient. –
Drugs are given to prevent or limit GVHD. These drugs increase the patient’s risk
of infection. However, GVHD that does not respond to treatment can lead to organ
damage or even death.
 ● NUTRITION PROBLEMS– The stomach and intestines are sensitive to
chemotherapy. Nausea, vomiting, mouth sores, diarrhea, and loss of appetite
may occur. – Typically, nutrition must be given through the veins until
patients are able to eat.
● INFERTILITY – Most patients who receive a transplant will not be able to
have their own children in the future. This is one (1) possible side effect of
drugs used while preparing for the transplant; however, there have been
patients who were able to conceive children after having a transplant.

TRANSFUSION
Blood transfusions are often critical for treating sickle cell disease. Transfusions
may be used either as treatment for specific episodes or as chronic transfusion
therapy to prevent life-threatening complications Ongoing transfusions can also
help improve height and weight in children with sickle cell disease. Normal
hemoglobin levels for patients with sickle cell disease are around 8 g/dL. Doctors
will try to keep the hemoglobin level no higher than 10 g/dL after transfusion.

⮚ EPISODIC TRANSFUSIONS: Episodic transfusions are needed in the

following situations:

● To manage sudden severe events, including acute chest syndrome, stroke,

widespread infection (septicemia), and multi-organ failure.
● To manage severe anemia, usually caused by splenic sequestration (dangerously
enlarged spleen) or aplasia (halting of red blood cell production, most often caused
by parvovirus). Transfusions are generally not required for mild or moderate
anemia.
● Before major surgeries. Transfusions are generally not required for minor
surgeries.

⮚ CHRONIC TRANSFUSIONS: Chronic (on-going) transfusions are used for:

● Stroke prevention for first or recurrent strokes. Evidence shows that regular (every
3 - 4 weeks) blood transfusions can reduce the risk of a first stroke by 90% in high-
risk children. In addition, studies indicate that as many as 90% of patients who
have experienced a stroke do not experience another stroke after 5 years of
transfusions. The U.S. National Institutes of Health strongly recommends that
doctors do not stop regular transfusions for children with sickle cell disease who
are at high risk for stroke.
● Pulmonary hypertension and chronic lung disease
● Heart failure
● Chronic kidney failure and severe anemia
● To reduce episodes of pain and acute chest syndrome
 Chronic blood transfusions carry their own risks, including iron overload,
alloimmunization (an immune response reaction), and exposure to blood borne
pathogens. Still, data from large-scale trials suggest that the risks for stroke
outweigh the risks associated with transfusions. Researchers are working on ways
to reduce the side effects associated with transfusion treatment.

COMPLICATIONS OF TRANSFUSION THERAPY.

● IMMUNE REACTIONS: An immune reaction may occur in response to donor
blood. In such cases, the patient develops antibodies that target and destroy the
transfused cells. This reaction, which can occur 5 - 20 days after transfusion, can
result in severe anemia and may be life-threatening in some cases. It can be
generally prevented with careful screening and matching of donor blood groups
before the transfusion
● HYPER VISCOSITY: With this condition, a mixture of hemoglobin S and
normal hemoglobin causes the blood to become sticky. The patient is at risk for
high blood pressure, altered mental status, and seizures. Careful monitoring can
prevent this condition.
● TRANSMISSION OF VIRAL ILLNESS: Before widespread blood screening,
transfusions were highly associated with a risk for hepatitis and HIV. This
complication has decreased considerably.
DRUG TREATMENTS

● Antibiotics, usually penicillin, are commonly given to infants and young children,
as well as adults, to help prevent infections.
● Pain relief medications ranging from nonprescription non-steroidal anti-
inflammatory drugs (NSAIDs) to opiods are given to control pain.
● Hydroxyurea is prescribed for patients with moderate-to-severe sickle cell disease
to help reduce the frequency of pain episodes and acute chest syndrome. It is
approved

HYDROXYUREA
HbF, also called fetal hemoglobin, is the form of hemoglobin present in the fetus
and small infants. Most HbF disappears early in childhood, although some HbF
may persist. Fetal hemoglobin is able to block the sickling action of red blood
cells. Because of this, infants with sickle cell disease do not develop symptoms of
the illness until. HbF levels have dropped.Hydroxyurea is a drug that reduces the
severity of sickle cell disease by stimulating production of HbF. It is currently the
only drug in general use to prevent acute sickle cell crises.

Hydroxyurea reduces the frequency of acute pain crises and episodes of acute chest
syndrome. It is taken daily by mouth. Hydroxyurea can be taken indefinitely and
the benefits appear to be long-lasting.

Hydroxyurea is not a cure-all. Not all patients respond to Hydroxyurea, and the
best candidates for the treatment are not yet clear. Many patients who can benefit
from it are not receiving it. Hydroxyurea is still being investigated for younger
patients. To date, the response to the drug in children with sickle cell disease is
similar to the response in adults, and few severe adverse effects are being reported.
Recent research also suggests that Hydroxyurea is safe for infants.

Side effects include constipation, nausea, drowsiness, hair loss, and inflammation
of the mouth. More severe side effects include reduction of white blood cells
(neutropenia) and clot-forming platelets (thrombocytopenia).

INVESTIGATIONAL TREATMENTS
● NITRIC OXIDE: Nitric oxide, a soluble gas, is a natural chemical in the
body that relaxes smooth muscles and expands blood vessels. Patients with
sickle cell disease are deficient in nitric oxide. This lack of nitric oxide
constricts blood vessels and causes pain in sickle cell diseases. In adult
patients, men may be more susceptible to this effect than women. Some
studies indicate that inhaling nitric oxide may slow the disease process and
improve symptoms in acute sickle cell crises.
● ARGININE: Arginine is involved in producing nitric oxide. Because a lack
of arginine may contribute to the development of pulmonary hypertension,
(a leading cause of death in patients with sickle cell disease), arginine is
being studied as a potential drug treatment. Some research is also being
conducted on arginine nutritional supplements. Patients should talk to their
doctors before taking these or any other supplements.

● DRUGS TO PREVENT DEHYDRATION: Researchers are studying

various drugs, as well as mineral supplements such as magnesium pidolate
and zinc sulfate, that may help prevent potassium loss and red blood cell
dehydration.
 MICROFLUIDIC CHIPS PROMISE BETTER DIAGNOSIS FOR
SICKLE CELL DISEASE:

Molecular biomarkers are useful as predictive indicators and can guide

intervention and treatment in many diseases. However, no reliable molecular
markers exist for SCD. A biophysical marker that holds great promise for helping
to determine the severity of sickle cell disease in patients, as well as developing
new treatment methods has been developed.

A micro fluidic device called SICKLE CELL CHIPS that mimics physiological
conditions in blood cells could aid the study of sickle cell anemia. The device can
characterize the dynamics of vaso-occlusion by measuring a biophysical parameter
that quantifies the rate of change of the resistance to flow. This can also indicate
disease severity and possibly be used to reduce the frequency of vaso-occlusive
crises.

For early diagnosis ofthis disorder, the micro fluidic platform recreates the size,
scale and pressures seen in the microvasculature in vivo, while simultaneously
control blood oxygen concentration.  The effects of deoxygenation on hemoglobin
polymerization can be studied through this micro fluidic sickle cell chips.

MECHANISM OF THE SICKLE CELL CHIPS:

Sickle blood flows through a micro channel, roughly the size of an arteriole or
venule, under constant pressure drop. The micro channel is diffusively coupled to a
gas reservoir in which the oxygen concentration was controlled by a custom-built
gas mixer. The oxygen concentration in the gas reservoir was measured in real
time using a fiber optic oxygen sensor inserted into the outlet of the gas reservoir,
which was under constant flow. This allowed real-time control for many
parameters that mimic the physiological conditions that occur during vaso-
occlusion, including channel size, blood pressure, and oxygen concentration.

To measure blood flow, a high-speed camera captured high frame rate video
sequences of flowing blood in real time. Cells in each video frame were identified
computationally based on morphologic criteria. Cell locations in subsequent
frames were linked to form trajectories using heuristics and machine learning
techniques. The velocity at each point in time as the median cell velocity is
calculated over a 32-frame video captured at higher than 200 frames per second.
Using the velocities computed from video tracking and the applied pressures, the
effective viscosity was calculated assuming Stokes flow through a rectangular
channel.

 A major innovation in diagnosis of this disease is the building of microchips that

actually show us what’s going on inside the human body.

With these devices, blood flows just like it does in the human body and we can
reproduce the same kind of complications in the chips that people with sickle cell
disease experience.

This approach allows many independent experiments to be performed in series,

while providing a way for the cells' mechanical and biochemical environment to be
precisely controlled.  Since a small number of cells can be enclosed in one droplet,
this approach can serve as a general system to isolate and measure the behavior of
single cells, following changes in the environment or addition of biochemical
reagents. This work is a good example of new information that may be obtained by
combining clever optical techniques with confined geometries. It to reduce
sufferings of people who suffer from this deadly disorder. This device will help
shed new light on the mechanisms involved in the disease and will provide a way
to explore the effects of potential drugs on sickle cells.

PROMISING RESULTS OF SICKLE CELL CHIPS:

As oxygen concentration in the blood is reduced, blood velocity remains constant

until a critical concentration of oxygen is reached. Once the oxygen concentration
drops below this threshold, the velocity decreases significantly, and at a lower
oxygen threshold, the blood fully occludes the micro channel. These oxygen
thresholds indicate where rheological changes can be expected to begin in the
vasculature and where occlusions are most likely to occur. The group also
measured the rate of change in viscosity during an in vitro vaso-occlusive event
and found that these measurements correlated very well with overall patient
disease severity.
Just by measuring a sickle cell patient’s blood in the device, it can be monitored
how the patients doing clinically and whether they are at risk for complications. In
this technique instead of monitoring individual molecules the emphasis is done on
measuring the fluid mechanical properties of the blood, and that can be used as
biomarkers.”
The idea of using micro devices to model human physiology is an exciting, rapidly
growing field with huge potential for treating a wide range of health conditions.
One big application of this technique is in diagnosis and clinical monitoring. Ever
bigger is the role of these chips in Drug development.

CONCLUSION:
If the new innovative method suggested by us is applied for the purpose of
diagnosis, then the life style of the infants can be regulated and monitored. This
can lead to fewer deaths and may contribute in reducing the sufferings of people
suffering through this disease.
 BIBLIOGRAPHY:
⮚ wikipedia.org
⮚ medicineandman.com
⮚ youngscientist.org
⮚ healthyheart.com
⮚ journal-science today

This is to certify that Gunjan Bhatia, Nandini Agrawal,

Khushi Saluja and Alisha Syed have completed their project
report successfully.

It is the record of original bonafide work carried out by them

under our guidance. They worked sincerely and have given a
satisfactory account of it in this project.

DATE: 26/10/2015

TEACHER INCHARGES:

Mrs. Pratibha Nair

Ms. Shweta Parashar

Mr. Shyam Agrawal

(PRINCIPAL)

DECLARATION

We Gunjan Bhatia, Nandini Agrawal, Khushi Saluja and

Alisha Syed, of Queens’ College, Indore solemnly declare that
the project entitled “SICKLED IS NO MORE CRIPPLED” is
the result of our own efforts under the guidance of our teachers.

DATE: 26/10/2014

NAMES: SIGNATURE

GUNJAN BHATIA XI “B”

NANDINI AGRAWAL X “B”
KHUSHI SALUJA IX “D”
ALISHA SYED IX “C”
 ACKNOWLEDGEMENT

We Gunjan Bhatia, Nandini Agrawal, Khushi Saluja and

Alisha Syed avail this opportunity to express our gratitude
towards respected Principal Sir, Mr. Shyam Agrawal for giving
us the valuable guidance and facilities to complete this work
successfully.

We are indebted and thankful to Madam Pratibha Nair and

Madam Shweta Parashar, our teachers under whose able and
purposeful guidance we could perform this project.
Cells in tissues need a steady supply of oxygen to work well. Normally,
haemoglobin in red blood cells takes up oxygen in the lungs and carries it to all the
tissues of the body. Red blood cells that contain normal haemoglobin are disc
shaped. This shape allows the cells to be flexible so that they can move through
large and small blood vessels to deliver oxygen. Sickle haemoglobin is not like
normal haemoglobin. It can form stiff rods within the red cell, changing it into a
crescent, or sickle shape.
The term sickle cell disease (SCD) describes a group of inherited red blood cell
disorders. People with SCD have abnormal haemoglobin, called haemoglobin S or
sickle haemoglobin, in their red blood cells. (Haemoglobin is a iron containing
cytochrome pigment in red blood corpuscles that carries oxygen throughout the
body)
“Inherited” means that the disease is passed by genes from parents to their
children. SCD is not contagious.
People who have SCD, inherit two abnormal haemoglobin genes, one from each
parent. In all forms of SCD, at least one of the two abnormal genes causes a
person’s body to make haemoglobin S. When a person has two haemoglobin S
genes, Haemoglobin SS, the disease is called sickle cell anaemia. This is the most
common and often most severe kind of SCD.

Sickle cell trait or the carrier state for sickle cell anaemia occurs in high frequency
among people of African-American and/or Hispanic descent, but it can also occur
in people of all ethnicities. When properly conducted, testing for
hemoglobinopathies also detects the carrier state for sickle cell disease and other
hemoglobinopathies.

It is a hereditary disorder that affects more than 13 million people around the
world. More than 800 children are born with SCD every day in Africa, and more
than half of them die in childhood due to lack of diagnosis and early treatment. The
sickle cell gene causes the body to produce abnormal haemoglobin. In sickle cell
disease, the haemoglobin clumps together, which causes red blood cells to become
stiff and develop a C-shaped (“sickle”) form. These sickled red blood cells can
block blood vessels, reducing blood flow in many parts of the body. This process
results in tissue and organ damage

NORMAL RED CELLS AND SICKLE RED CELLS:

Figure A shows normal red blood cells flowing freely in a blood vessel. The inset
image shows a cross-section of a normal red blood cell with normal haemoglobin.
Figure B shows abnormal, sickled red blood cells blocking blood flow in a blood
vessel. The inset image shows a cross-section of a sickle cell with abnormal
(sickle) haemoglobin forming abnormal stiff rods.

HAEMOGLOBIN AND IRON:

● Each red blood cell contains about 280 million hemoglobin molecules.
Hemoglobin is the most important component of red blood cells. It is composed of
protein (globulin) and a molecule (heme), which binds to iron.
● In the lungs, the heme component takes up oxygen and releases carbon dioxide.
The red blood cells carry the oxygen to the body's tissues, where the hemoglobin
releases the oxygen in exchange for carbon dioxide, and the cycle repeats. The
oxygen is essential for all cells in the body to function.
● Sickle cell disease reduces or denies adequate oxygen to many parts of the body.
This contributes to the severe pain experienced as a sickle cell crisis and both short-
and long-term organ damage.
 WHY DID WE CHOOSE THIS TOPIC?

The main purpose of this research is to develop a system that could measure the
complex rheological properties of sickle blood as it passes through small blood
vessels with decreasing oxygen levels. People of all age groups lose their lives due
to lack in early diagnostic procedures.
 ● FOREIGN COUNTRY:

The disease originated in at least 4 places in Africa and in the Indian/Saudi

Arabian subcontinent. It exists in all countries of Africa and in areas where
Africans have migrated.
It is most common in West and Central Africa where as many as 25% of the people
have sickle cell trait and 1-2% of all babies are born with a form of the disease. In
the United States with an estimated population of over 270 million, about 1,000
babies are born with sickle cell disease each year. Approximately 70,000 - 100,000
individuals in the United States have sickle cell disease and 3 million have sickle
cell trait. In contrast, Nigeria, with an estimated 1997 population of 90 million,
45,000-90,000 babies with sickle cell disease are born each year.
The transatlantic slave trade was largely responsible for introducing the sickle cell
gene into the Americas and the Caribbean. However, sickle cell disease had
already spread from Africa to Southern Europe by the time of the slave trade, so it
is present in Portuguese, Spaniards, French Corsicans, Sardinians, and Sicilians,
mainland Italians, Greeks, Turks and Cypriots. Sickle cell disease appears in most
of the near and Middle East countries including Lebanon, Israel, Saudi Arabia,
Kuwait and Yemen.
The condition has also been reported in India and Sri Lanka. Sickle cell disease is
an international health problem and truly a global challenge.

Sickle cell disease (SCD) affects millions of people throughout the world and is
particularly common among those whose ancestors came from sub-Saharan Africa;
Spanish-speaking regions in the Western Hemisphere (South America, the
Caribbean, and Central America); Saudi Arabia; India; and Mediterranean
countries such as Turkey, Greece, and Italy.
Sickle cell disease occurs more often among people from parts of the world where
malaria is or was common. It is believed that people who carry the sickle cell trait
are less likely to have severe forms of malaria.
IN THE UNITED STATES
The exact number of people living with SCD in the U.S. is unknown. However, the
CDC in collaboration with the National Institutes of Health and 7 states
(California, Florida, Georgia, North Carolina, New York, Michigan and
Pennsylvania) are coordinating the Registry and Surveillance System for
Hemoglobinopathies(RuSH) project to learn about the number of people living
with SCD to better understand how the disease impacts their health.

It is estimated that:

● SCD affects 90,000 to 100,000 Americans.

● SCD occurs among about 1 out of every 500 Black or African-American
births.
● SCD occurs among about 1 out of every 36,000 Hispanic-American births.
● SCT occurs among about 1 in 12 Blacks or African Americans.

MORTALITY
Sickle cell-related death among Black or African-American children younger than
4 years of age fell by 42% from 1999 through 2002. This drop coincided with the
introduction in 2000 of a vaccine that protects against invasive pneumococcal
disease.
RELATIVE TO THE RATE FOR THE PERIOD 1983 THROUGH 1986,
THE SCD MORTALITY RATE FOR THE PERIOD 1999 THROUGH 2002
DECREASED BY:
● 68% at age 0 through 3 years;
● 39% at age 4 through 9 years; and
● 24% at age 10 through 14 years.

MORTALITY AMONG CHILDREN WITH SICKLE CELL DISEASE:

Among the children with Hb SS disease, 1% died as a result of SCD-related causes
during the first 3 years of life.In California and Illinois, by the end of 1995, the
cumulative mortality rate was 1.5 per 100 Black or African-American children
with SCD. The equivalent cumulative mortality rate for all Black or African-
American infants born during this period in California and Illinois was 2.0 per 100
Black or African-American newborns.
ECONOMIC COSTS:
During 2005, medical expenditures for children with SCD averaged $11,702 for
children with Medicaid coverage and $14,772 for children with employer-
sponsored insurance. About 40% of both groups had at least one hospital stay.
SCD is a major public health concern. From 1989 through 1993, an average of
75,000 hospitalizations due to SCD occurred in the United States, costing
approximately $475 million.

THE CASE IN INDIA:

The state Lokayukta had directed the public health department to conduct primary
population survey to determine the prevalence of sickle cell disease. Though the
department did not conduct the survey, it helped a non-governmental organization
with a similar survey. The report says 10.5% of the tribal population,
approximately 9,45,000 persons, are affected by the disease in Maharashtra.

Sickle Cell Disease International Organization (SCDIO) conducted the survey in

states of Maharashtra, Gujarat, Orissa, Madhya Pradesh and Tamil Nadu. The
effort was aimed at creating awareness on sickle-cell anaemia and to seek
government support to list the disease in the National Rural Health Mission.
SCDIO wants to make India SCD free.

"SCDIO has started an advocacy to consider SCD as a priority disease, by

conducting meetings with the central government and state ministries of health and
family welfare. We also plan to start Caravan Project to screen the population for
SCD in some states with high prevalence, and thereafter in other states with the
help of government and non-government organizations," said Dr. Hariom Sharma,
Global Scientific Coordinator of SCDIO. Agencies like department of health and
family welfare of the central government and various states and Indian Council of
Medical Research were also involved in the survey, he added.

The report of the organization reveals that nearly 20 million children are born with
sickle-cell anaemia in India every year. With its present rate of spread, in another
25-40 years, over 1.5 crore children will suffer and die of sickle-cell disease, and
over 3 crore person will inherit the abnormal haemoglobin trait, says the report.

About the prevalence of the disease in Maharashtra, the report counts 10.5% of the
tribal population, approximately 9, 45,000 people, as affected by the disease.
While the overall incidence of the disease in the state is less than 0.1%, it is very
high among the tribal population groups from Nan durbar and Gadchiroli districts.
The overall prevalence among tribal populations is about 10% for carriers of the
disease and 0.5% for sufferers. The same tribal population groups residing in
neighbouring states of Gujarat, Madhya Pradesh and Andhra Pradesh have a
similar prevalence.
Sickle cell anemia is caused by a mutation in the gene that tells your body to make
hemoglobin — the red, iron-rich compound that gives blood its red color.
Hemoglobin allows red blood cells to carry oxygen from your lungs to all parts of
your body. In sickle cell anemia, the abnormal hemoglobin causes red blood cells
to become rigid, sticky and misshapen.

The sickle cell gene is passed from generation to generation in a pattern of

inheritance called autosomal recessive inheritance. This means that both the
mother and the father must pass on the defective form of the gene for a child to be
affected.
Abnormal hemoglobin, called hemoglobin S, causes sickle cell disease (SCD). The
problem in hemoglobin S is caused by a small defect in the gene that directs the
production of the beta globin part of hemoglobin. This small defect in the beta
globin gene causes a problem in the beta globin part of hemoglobin, changing the
way that hemoglobin works
HOW IS SICKLE CELL DISEASE INHERITED?

● When the hemoglobin S gene is inherited from only one parent and a normal
hemoglobin gene is inherited from the other, a person will have sickle cell trait.

● People with sickle cell trait are generally healthy. Only rarely do people with
sickle cell trait have complications similar to those seen in people with SCD.

● But people with sickle cell trait are carriers of a defective hemoglobin S gene.
So, they can pass it on when they have a child. If the child’s other parent also
has sickle cell trait or another abnormal hemoglobin gene (like thalassemia,
hemoglobin C, hemoglobin D, hemoglobin E), that child has a chance of having
SCD.

● If only one parent passes the sickle cell gene to the child, that child will have
the sickle cell trait. With one normal hemoglobin gene and one defective form
of the gene, people with the sickle cell trait make both normal hemoglobin and
sickle cell hemoglobin. Their blood may contain some sickle cells, but they
generally don't experience symptoms. However, they are carriers of the disease,
which means they can pass the defective gene on to their children.

The image shows how sickle hemoglobin genes are inherited. A person inherits
two hemoglobin genes—one from each parent. A normal gene will make normal
hemoglobin (A). A sickle hemoglobin gene will make abnormal hemoglobin (S).

In the image below, each parent has one hemoglobin A gene and one hemoglobin S
gene, and each of their children has:
 RISK OF INHERITANCE

People inherit a pair of genes that regulate hemoglobin, with one gene coming
from each parent. If two sickle genes are inherited, a person will have sickle cell
disease. If a one normal hemoglobin gene and one sickle cell gene are inherited, a
person will have sickle cell trait. People who have sickle cell trait are healthy and
do not develop themselves sickle cell disease, but they are “carriers” who can pass
the disease on to their children.

The risk of a child inheriting sickle cell disease or sickle cell trait is as follows:

● If both parents have sickle cell trait (each have one normal hemoglobin gene and
one sickle cell gene), the child has a 50% chance of inheriting sickle cell trait (one
 normal gene, one sickle cell gene), 25% chance of inheriting sickle cell disease
(two sickle cell genes), and 25% chance of not inheriting either the trait or the
disease (two normal genes).

● If one parent has sickle cell trait (one normal gene and one sickle cell gene) and the
other parent has two normal hemoglobin genes, the child has a 50% chance of
inheriting sickle cell trait (one normal gene and one sickle cell gene) and a 50% of
inheriting neither the trait nor the disease (two normal genes). The child is not at
risk of inheriting sickle cell disease.

● If one parent has sickle cell disease (two sickle cell genes) and the other parent has
sickle cell trait (one normal gene, one sickle cell gene), the child has a 50% chance
of inheriting sickle cell trait and a 50% chance of inheriting sickle cell disease.

● If one parent has sickle cell disease and the other parent has two normal
hemoglobin genes, the child has a 100% chance of inheriting sickle cell trait, but
not the disease.

● If both parents have sickle cell disease, the child has a 100% chance of inheriting
the disease.

TYPE OF MUTATION OBSERVED:

Type of mutation observed in SCD is substitution.
A substitution is a mutation that exchanges one base for another (i.e., a change in
a single "chemical letter" such as switching an A to a G). Such a substitution could:
● Change a codon to one that encodes a different amino acid and cause a small
change in the protein produced. For example, sickle cell anaemia is caused
by a substitution in the beta-haemoglobin gene, which alters a single amino
acid in the protein produced.
● Change a codon to one that encodes the same amino acid and causes no
change in the protein produced. These are called silent mutations.
● Change an amino-acid-coding codon to a single "stop" codon and cause an
incomplete protein. This can have serious effects since the incomplete
protein probably won't function.
EFFECTS OF MUTATION: SICKLE CELL ANEMIA
The mutations that cause sickle cell anemia have been extensively studied and
demonstrate how the effects of mutations can be traced from the DNA level up to
the level of the whole organism. Consider someone carrying only one copy of the
gene. She does not have the disease, but the gene that she carries still affects her,
her cells, and her proteins:

3. There are effects at the DNA level

4. There are effects at the protein level

Normal hemoglobin and hemoglobin in sickled red blood cells look
different; the mutation in the DNA slightly changes the shape of the
hemoglobin molecule, allowing it to clump together.
Signs and symptoms of sickle cell anemia often don't appear until an infant is
at least 4 months old and may include:

● ANEMIA: Sickle cells are fragile. They break apart easily and die, leaving you
without a good supply of red blood cells. Red blood cells usually live for about
120 days before they die and need to be replaced. But sickle cells die after an
average of less than 20 days. This results in a lasting shortage of red blood cells
(anemia). Without enough red blood cells in circulation, your body can't get the
oxygen it needs to feel energized. That's why anemia causes 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. The pain may vary in intensity and
can last for a few hours to a few weeks. Some people experience only a few
episodes of pain. Others experience a dozen or more crises a year. If a crisis is
severe enough, you may need to be hospitalized.

● HAND FOOT SYNDROME: Swollen hands and feet may be the first signs of
sickle cell anemia in babies. The swelling is caused by sickle-shaped red blood
cells blocking blood flow out of their hands and feet. Hand-foot syndrome,
 also called palmar-plantar erythrodysesthesia, is a side effect of some types of
chemotherapy. 

Hand-foot syndrome causes redness, swelling, and pain on the palms of

the hands and/or the soles of the feet.

● VISION PROBLEMS: Some people with sickle cell anemia experience 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.
● GENERAL SYMPTOMS IN CHILDREN: Pain is the most common
complaint. It can be acute and severe or chronic, usually from orthopedic
problems in the legs and low back. Other symptoms include:

● Fatigue and shortness of breath (signs of anemia)

● Irritability
● Jaundice (yellowish discoloration of the skin and eyes)

● ADDITIONAL SYMPTOMS IN ADOLESCENCE OR ADULTHOOD:

Symptoms of childhood continue in adolescence and adulthood. In addition,
patients may experience.

● DELAYED PUBERTY (IN YOUNG TEENAGERS)

● SEVERE JOINT PAIN

● PROGRESSIVE ANEMIA
● LEG SORES
● GUM DISEASE
 ● FREQUENT INFECTIONS: Sickle cells can damage your spleen, an organ
that fights infection. This may make 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.

THE SICKLE CELL DISEASE PROCESS

The symptoms and problems of sickle cell disease are a result of the hemoglobin S
(HbS) molecule:

● When the sickle hemoglobin molecule loses its oxygen, it forms rigid rods called
polymers that change the red blood cells into a sickle or crescent shape.
● These sickle-shaped cells stick to the walls and cannot squeeze through the
capillaries. Blood flow through tiny blood vessels becomes slowed or stopped in
many parts of the body. This deprives tissues and organs of oxygen.
● When this blood flow slows or stops suddenly in a certain part of the body, the
decrease in oxygen (hypoxia) can cause severe pain (the sickle cell crisis). Over
time, it leads to gradual destruction in organs and tissues throughout the body.
● The higher the concentration of sickle hemoglobin and the more acidic the
environment, the faster the sickle cell process.
● When blood cells dry out (dehydrate), the density of hemoglobin S within the cell
increases, thereby speeding the sickling process.
● Sickle cells also have a shorter life span (10 - 20 days) than that of normal red
blood cells (90 - 120 days). Every day the body produces new red blood cells to
replace old ones, but sickle cells become destroyed so fast that the body cannot
keep up. The red blood cell count drops, which results in anemia. This gives sickle
cell disease its more common name, sickle cell anemia.
 INTERVIEW:

3. DR.RAJKUMAR AGRAWAL:
4. DR.A SABARWAL:

We had an elaborated interview with both the specialized dr. who gave us
several information about sickle cell anaemia. According to them sickle cell
anaemia is a severe disease which is inherited from parents to offspring’s.
People at risk for inheriting the gene for sickle cell descend from people who
 are or were originally from Africa and parts of India and the Mediterranean.
Sickle cell disease changes normal, round red blood cells into cells that can be
shaped like crescent moons. Because of this disease many people are dying
worldwide. This disease needs to be diagnosed otherwise this may affect our
population very badly. They told us about unawareness of people regarding this
disease. They gave us several traditional method upon which this disease can be
taken care of. Not only this they both seemed very happy after looking our
enthusiasm towards this severe disease and the way are we trying to absolve it.

CASE STUDIES:

Here is a case study taken from worldwide about the people who are suffering
from SICKE CELL ANAEMIA and their experience which was shared by his
parents.
On the morning of admission, our patient, a 19-year-old African-American man
with sickle cell anaemia, felt himself to be in his usual state of health, although he
had just been discharged the previous day from a hospitalization for acute chest
syndrome.. However, at approximately 5:45 p.m., he noticed that he could not pull
up his trousers due to weakness in his left arm. As he walked out , he noted that he
was having difficulty walking because of weakness in his right and left leg. He
began experiencing ‘shocking’ pains on both sides of his neck, which were unlike
his usual pain, and also noted that he had an erection. These events transpired
rapidly, within about six minutes, at which point his family called Emergency
Medical Services (EMS) and our patient was transported to hospital.

On arrival at our hospital, he was alert and oriented and cranial nerves II to XII
were intact. He had flaccid paralysis of the bilateral upper extremities and the left
lower extremity.. The results of the rest of his physical examination were normal.

Relevant medical history included asthma, recurrent acute chest syndrome and
intermittent attempts at Hydroxyurea. He was treated for the three years with
exchange transfusions to maintain hemoglobin S < 30 percent; during this time he
did very well. At 10 days prior to presentation, he was hospitalized with an acute
chest syndrome.. He was treated with antibiotics and a transfusion. His discharge
hemoglobin was 6.6 and oxygen saturation 96 percent. He was without symptoms
at the time of discharge.

The results of peripheral blood and urine cultures were negative. A chest X-ray
showed patchy consolidation in the right upper lobe suspicious for pneumonia. The
results of computed tomography (CT) angiography of the head and neck were
unremarkable.

Later the initial MRI was read to also show swelling of the cord in the same area.
He was admitted to the neurologic intensive care unit where he received an
exchange transfusion with no significant improvement in his symptoms
andsubsequent hemoglobin electrophoresis. While in the intensive care unit (ICU)
he experienced episodes of hypotension that were initially managed with
vasopressors. His erythrocyte sedimentation rate (ESR) and C-reactive protein
(CRP) levels were both elevated, and proteins C and S were found to be low but
within the expected range for someone with sickle cell disease. He was anti-
coagulated with a heparin drip during his stay in the acute care facility, but this
was discontinued on discharge. A monthly exchange transfusion regimen was
instituted with the goal of keeping his haemoglobin S level. Currently, at 20
months post-spinal cord infarction, his condition is unchanged.

SURVEYS:

Here is a survey done by our queens. Our queens surveyed three people Palak
Dubey, Avantika Joshi and Sharad Agrawal who are been suffering through this
disease. They shared their experience with us.

Common conclusion:
Out of the three surveys that we conducted all the patients had problem in
managing their normal routines. No medicines are there to rectify the error.
They were thrilled to learn about the new painless method of early diagnosis of the
problem. They enquired about the application of this diagnostic chip in INDIA and
its availability.
Lack in early diagnosis can lead to severe ill effects on health and can lead to
following complications:

1)INFECTIONS: Late diagnosis may lead to increased risk of severe bacterial

infections due to loss of functioning spleen tissue. These infections are typically
caused by encapsulated organisms such as Streptococcus pneumonia and
hemophilic influenza.

2)STROKE: Stroke which can result from a progressive narrowing of blood

vessels prevents oxygen from reaching the brain. Cerebral infraction occurs in
children and cerebral hemorrhage in adults. A cerebral infarction is a type of
ischemic stroke resulting from a blockage in the blood vessels supplying blood to
the brain. It can be atherothrombotic or embolic. Stroke caused by cerebral
infarction should be distinguished from two other kinds of stroke: cerebral
hemorrhage and subarachnoid hemorrhage.

3)SILENT STROKE: It causes no immediate symptoms, but is associated with

damage to the brain. Silent stroke is probably five times as common as
symptomatic stroke. About 10–15% of children with SCD suffer strokes, with
silent strokes predominating in the younger patients.

4)CHOLELITHIASIS AND CHOLECYSTITIS: Lack in early diagnosis can

lead to Cholelithiasis which is a medical term used for Gall Stones which are
concretions that form in the biliary tract, usually in the Gall bladder. It can also
lead to Cholecystitis which is inflammation of the Gall Bladder.
5)VASCULAR NECROSIS: Complications like Avascular necrosis may arise.
Avascular necrosis is the death of bone tissues due to a lack of blood supply. This
is also referred to as Osteonecrosis as it can lead to tiny breaks in the bone and the
bone’s eventual death. Avascular necrosis of the hip and other major joints may
occur as a result of ischemia. Ischemia is a restriction in blood supply to the
tissues, causing a shortage of oxygen and glucose needed for cellular metabolism.

6)OSTEOMYELITIS: Osteomyelitis is the inflammation of bone or bone

marrow, usually due to infection. The most common cause of Osteolyelitis in SCD
is Salmonella.

7)PULMONARY HYPERTENSION: Pulmonary hypertension (PH) is an

increase of blood pressure in the pulmonary artery, pulmonary vein,
or pulmonary capillaries, together known as the lung vasculature, leading to
shortness of breath, dizziness, fainting, leg swelling, episodes of syncope,
decreased exercise tolerance, increased risk of heart failures and other
symptoms.21% of children and 30% of adults have evidence of pulmonary
hypertension when tested.
8)CHRONIC KIDNEY FAILURE: It occurs due to sickle-cell nephropathy
manifests itself with hypertension, protein loss in the urine, loss of red blood cells
in urine and worsened anemia. Sickle cell nephropathy is a type of nephropathy
(kidney disease) associated with sickle cell disease, it causes kidney complications
as a result of sickling of red blood cells in the small blood vessels.If it progresses
to end-stage renal failure, it carries a poor prognosis.

9)DURING PREGNANCY: A pregnant lady can suffer from the following

complications if she is suffering from Sickle cell disease :

a)intrauterine growth retardation : It refers to poor growth of a fetus

while in the mother's womb during pregnancy. The causes can be many, but most
often involve poor maternal nutrition or lack of adequate oxygen supply to the
fetus.

b)spontaneous abortion

c)pre-eclampsia: a condition in pregnancy characterized by high blood

pressure, sometimes with fluid retention and proteinuria.

10)EYE DAMAGE: In eyes, background retinopathy, proliferative retinopathy,

vitreous hemorrhages, and retinal detachments can result in blindness.
11)ACUTE CHEST SYNDROME (ACS): Acute chest syndrome occurs when
the lung tissues are deprived of oxygen during a crisis. It can be very painful,
dangerous, and even life threatening. It is a leading cause of illness among sickle
cell patients and is the most common condition at the time of death.

12)CHRONIC PAIN: Even in the absence of acute vaso-occlusive pain, many

patients have unreported chronic pain.
HEMOGLOBIN ELECTROPHORESIS:
Sickle-shaped red blood cells can be seen when a blood sample is examined under
a microscope. But sickle cell disease is diagnosed by a blood test called
hemoglobin electrophoresis, which measures the amount of the abnormal sickle
hemoglobin. The amount of sickle hemoglobin determines whether the person is a
carrier (sickle cell trait) or has sickle cell disease.

 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. The sample is
then sent to a laboratory, where it's screened for hemoglobin S.
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. People who have one gene — sickle cell trait — have a
fairly small percentage of hemoglobin S. People with two genes — sickle cell
anemia — have a much larger percentage of the defective hemoglobin.

ADDITIONAL TESTS:
To confirm any diagnosis, a sample of blood is examined under a microscope to
check for large numbers of sickle cells — a marker of the disease. If you or your
child has the disease, a blood test to check for anemia — a low red blood cell count
— will be done. And your doctor may suggest additional tests to check for possible
complications of the disease.
If you or your child carries the sickle cell gene, you may be referred to a genetic
counselor — an expert in genetic diseases.

TESTS TO DETECT SICKLE CELL GENES BEFORE BIRTH:

Sickle cell disease can be diagnosed in an unborn baby by sampling some of the
fluid surrounding the baby in the mother's womb (amniotic fluid) to look for the
sickle cell gene. If you or your partner has been diagnosed with sickle cell anemia
or sickle cell trait, ask your doctor about whether you should consider this
screening. 

TRANSCRANIAL DOPPLER (TCD) ULTRASONOGRAPHY:

● The Transcranial Doppler (TCD) and the more recent trans cranial color

Doppler (TCCD) are tests that measure the velocity of blood flow through
the brain’s blood vessels.
● This test can probably detect the sickle cell disease.
 ● The tests are often used in conjunction with other tests such
as MRI, MRA, carotid duplex ultrasound and CT scans.

MAGNETIC RESONANCE IMAGING (MRI)

● The use of follow-up magnetic resonance imaging (MRI) to detect small blockages
in blood vessels may help confirm high risk in patients identified by TCD
ultrasound.

ANGIOGRAPHY:

Some patients may need to undergo angiography, an invasive diagnostic technique

useful for detecting aneurysms. Angiography or arteriography is a medical
imaging technique used to visualize the inside, or lumen, of blood vessels and
organs of the body, with particular interest in the arteries, veins, and the heart
chambers.
Treatment goals for sickle cell disease aim to relieve pain, prevent infections, and
manage complications.

There is still no cure for sickle cell disease other than experimental transplantation
procedures, but treatments for complications of sickle cell have prolonged the lives
of many patients who are now living into adulthood.

BONE MARROW TRANSPLANTATION

Stem cell transplantation is a potential cure for sickle cell disease. Stem cells can

be found in bone marrow. Bone marrow is the substance in the center of your
bones that produces red blood cells. A person with sickle cell disease has bone
marrow that produces red blood cells with defective hemoglobin S. But if that bone
marrow is replaced with healthy bone marrow, a person's body may start to
produce normal hemoglobin.
Stem cell transplants require bone marrow from another person (donor). This is
called an allogeneic stem cell transplant.
Before the transplant, bone marrow stem cells are taken from someone who has
closely matching bone marrow, usually a healthy brother or sister. The child who
has sickle cell disease is then treated with drugs that destroy his or her bone
marrow cells. After that, the donated bone marrow stem cells are injected into a
vein.
After the process is complete, the donor's bone marrow begins to replace the
recipient's bone marrow. These new cells restore the immune system and make
normal red blood cells.
THE POSSIBLE RISKS OF TRANSPLANT:
● Infections – Chemotherapy lowers the white blood cells, which normally
fight and prevent infections. – This puts the patient at high risk for
infections, which can be caused by bacteria, fungi, or viruses. – Medicines
are given to fight these germs and prevent these infections. Infections that do
not respond to the treatment can lead to death in 5 to 10 percent of patients.
● Graft-versus-host disease (GVHD) –

This reaction occurs when the immune cells of the donor (graft cells) sense that
cells of the patient (host cells) are different and attack them. This can be a serious
side effect of transplant. – GVHD occurs in up to 10 percent of patients who
undergo matched related types of transplants. It can be higher in transplants using
other donors. – This condition can be acute (occurring less than 100 days after the
transplant) or chronic (occurring more than 100 days after transplant). – It may
cause damage to the skin, liver, and intestinal tract of the transplanted patient. –
Drugs are given to prevent or limit GVHD. These drugs increase the patient’s risk
of infection. However, GVHD that does not respond to treatment can lead to organ
damage or even death.
 ● NUTRITION PROBLEMS– The stomach and intestines are sensitive to
chemotherapy. Nausea, vomiting, mouth sores, diarrhea, and loss of appetite
may occur. – Typically, nutrition must be given through the veins until
patients are able to eat.
● INFERTILITY – Most patients who receive a transplant will not be able to
have their own children in the future. This is one (1) possible side effect of
drugs used while preparing for the transplant; however, there have been
patients who were able to conceive children after having a transplant.

TRANSFUSION
Blood transfusions are often critical for treating sickle cell disease. Transfusions
may be used either as treatment for specific episodes or as chronic transfusion
therapy to prevent life-threatening complications Ongoing transfusions can also
help improve height and weight in children with sickle cell disease. Normal
hemoglobin levels for patients with sickle cell disease are around 8 g/dL. Doctors
will try to keep the hemoglobin level no higher than 10 g/dL after transfusion.

⮚ EPISODIC TRANSFUSIONS: Episodic transfusions are needed in the

following situations:

● To manage sudden severe events, including acute chest syndrome, stroke,

widespread infection (septicemia), and multi-organ failure.
● To manage severe anemia, usually caused by splenic sequestration (dangerously
enlarged spleen) or aplasia (halting of red blood cell production, most often caused
by parvovirus). Transfusions are generally not required for mild or moderate
anemia.
● Before major surgeries. Transfusions are generally not required for minor
surgeries.

⮚ CHRONIC TRANSFUSIONS: Chronic (on-going) transfusions are used for:

● Stroke prevention for first or recurrent strokes. Evidence shows that regular (every
3 - 4 weeks) blood transfusions can reduce the risk of a first stroke by 90% in high-
risk children. In addition, studies indicate that as many as 90% of patients who
have experienced a stroke do not experience another stroke after 5 years of
transfusions. The U.S. National Institutes of Health strongly recommends that
doctors do not stop regular transfusions for children with sickle cell disease who
are at high risk for stroke.
● Pulmonary hypertension and chronic lung disease
● Heart failure
● Chronic kidney failure and severe anemia
● To reduce episodes of pain and acute chest syndrome
 Chronic blood transfusions carry their own risks, including iron overload,
alloimmunization (an immune response reaction), and exposure to blood borne
pathogens. Still, data from large-scale trials suggest that the risks for stroke
outweigh the risks associated with transfusions. Researchers are working on ways
to reduce the side effects associated with transfusion treatment.

COMPLICATIONS OF TRANSFUSION THERAPY.

● IMMUNE REACTIONS: An immune reaction may occur in response to donor
blood. In such cases, the patient develops antibodies that target and destroy the
transfused cells. This reaction, which can occur 5 - 20 days after transfusion, can
result in severe anemia and may be life-threatening in some cases. It can be
generally prevented with careful screening and matching of donor blood groups
before the transfusion
● HYPER VISCOSITY: With this condition, a mixture of hemoglobin S and
normal hemoglobin causes the blood to become sticky. The patient is at risk for
high blood pressure, altered mental status, and seizures. Careful monitoring can
prevent this condition.
● TRANSMISSION OF VIRAL ILLNESS: Before widespread blood screening,
transfusions were highly associated with a risk for hepatitis and HIV. This
complication has decreased considerably.
DRUG TREATMENTS

● Antibiotics, usually penicillin, are commonly given to infants and young children,
as well as adults, to help prevent infections.
● Pain relief medications ranging from nonprescription non-steroidal anti-
inflammatory drugs (NSAIDs) to opiods are given to control pain.
● Hydroxyurea is prescribed for patients with moderate-to-severe sickle cell disease
to help reduce the frequency of pain episodes and acute chest syndrome. It is
approved

HYDROXYUREA
HbF, also called fetal hemoglobin, is the form of hemoglobin present in the fetus
and small infants. Most HbF disappears early in childhood, although some HbF
may persist. Fetal hemoglobin is able to block the sickling action of red blood
cells. Because of this, infants with sickle cell disease do not develop symptoms of
the illness until. HbF levels have dropped.Hydroxyurea is a drug that reduces the
severity of sickle cell disease by stimulating production of HbF. It is currently the
only drug in general use to prevent acute sickle cell crises.

Hydroxyurea reduces the frequency of acute pain crises and episodes of acute chest
syndrome. It is taken daily by mouth. Hydroxyurea can be taken indefinitely and
the benefits appear to be long-lasting.

Hydroxyurea is not a cure-all. Not all patients respond to Hydroxyurea, and the
best candidates for the treatment are not yet clear. Many patients who can benefit
from it are not receiving it. Hydroxyurea is still being investigated for younger
patients. To date, the response to the drug in children with sickle cell disease is
similar to the response in adults, and few severe adverse effects are being reported.
Recent research also suggests that Hydroxyurea is safe for infants.

Side effects include constipation, nausea, drowsiness, hair loss, and inflammation
of the mouth. More severe side effects include reduction of white blood cells
(neutropenia) and clot-forming platelets (thrombocytopenia).

INVESTIGATIONAL TREATMENTS
● NITRIC OXIDE: Nitric oxide, a soluble gas, is a natural chemical in the
body that relaxes smooth muscles and expands blood vessels. Patients with
sickle cell disease are deficient in nitric oxide. This lack of nitric oxide
constricts blood vessels and causes pain in sickle cell diseases. In adult
patients, men may be more susceptible to this effect than women. Some
studies indicate that inhaling nitric oxide may slow the disease process and
improve symptoms in acute sickle cell crises.
● ARGININE: Arginine is involved in producing nitric oxide. Because a lack
of arginine may contribute to the development of pulmonary hypertension,
(a leading cause of death in patients with sickle cell disease), arginine is
being studied as a potential drug treatment. Some research is also being
conducted on arginine nutritional supplements. Patients should talk to their
doctors before taking these or any other supplements.

● DRUGS TO PREVENT DEHYDRATION: Researchers are studying

various drugs, as well as mineral supplements such as magnesium pidolate
and zinc sulfate, that may help prevent potassium loss and red blood cell
dehydration.
 MICROFLUIDIC CHIPS PROMISE BETTER DIAGNOSIS FOR
SICKLE CELL DISEASE:

Molecular biomarkers are useful as predictive indicators and can guide

intervention and treatment in many diseases. However, no reliable molecular
markers exist for SCD. A biophysical marker that holds great promise for helping
to determine the severity of sickle cell disease in patients, as well as developing
new treatment methods has been developed.

A micro fluidic device called SICKLE CELL CHIPS that mimics physiological
conditions in blood cells could aid the study of sickle cell anemia. The device can
characterize the dynamics of vaso-occlusion by measuring a biophysical parameter
that quantifies the rate of change of the resistance to flow. This can also indicate
disease severity and possibly be used to reduce the frequency of vaso-occlusive
crises.

For early diagnosis ofthis disorder, the micro fluidic platform recreates the size,
scale and pressures seen in the microvasculature in vivo, while simultaneously
control blood oxygen concentration.  The effects of deoxygenation on hemoglobin
polymerization can be studied through this micro fluidic sickle cell chips.

MECHANISM OF THE SICKLE CELL CHIPS:

Sickle blood flows through a micro channel, roughly the size of an arteriole or
venule, under constant pressure drop. The micro channel is diffusively coupled to a
gas reservoir in which the oxygen concentration was controlled by a custom-built
gas mixer. The oxygen concentration in the gas reservoir was measured in real
time using a fiber optic oxygen sensor inserted into the outlet of the gas reservoir,
which was under constant flow. This allowed real-time control for many
parameters that mimic the physiological conditions that occur during vaso-
occlusion, including channel size, blood pressure, and oxygen concentration.

To measure blood flow, a high-speed camera captured high frame rate video
sequences of flowing blood in real time. Cells in each video frame were identified
computationally based on morphologic criteria. Cell locations in subsequent
frames were linked to form trajectories using heuristics and machine learning
techniques. The velocity at each point in time as the median cell velocity is
calculated over a 32-frame video captured at higher than 200 frames per second.
Using the velocities computed from video tracking and the applied pressures, the
effective viscosity was calculated assuming Stokes flow through a rectangular
channel.

 A major innovation in diagnosis of this disease is the building of microchips that

actually show us what’s going on inside the human body.

With these devices, blood flows just like it does in the human body and we can
reproduce the same kind of complications in the chips that people with sickle cell
disease experience.

This approach allows many independent experiments to be performed in series,

while providing a way for the cells' mechanical and biochemical environment to be
precisely controlled.  Since a small number of cells can be enclosed in one droplet,
this approach can serve as a general system to isolate and measure the behavior of
single cells, following changes in the environment or addition of biochemical
reagents. This work is a good example of new information that may be obtained by
combining clever optical techniques with confined geometries. It to reduce
sufferings of people who suffer from this deadly disorder. This device will help
shed new light on the mechanisms involved in the disease and will provide a way
to explore the effects of potential drugs on sickle cells.

PROMISING RESULTS OF SICKLE CELL CHIPS:

As oxygen concentration in the blood is reduced, blood velocity remains constant

until a critical concentration of oxygen is reached. Once the oxygen concentration
drops below this threshold, the velocity decreases significantly, and at a lower
oxygen threshold, the blood fully occludes the micro channel. These oxygen
thresholds indicate where rheological changes can be expected to begin in the
vasculature and where occlusions are most likely to occur. The group also
measured the rate of change in viscosity during an in vitro vaso-occlusive event
and found that these measurements correlated very well with overall patient
disease severity.
Just by measuring a sickle cell patient’s blood in the device, it can be monitored
how the patients doing clinically and whether they are at risk for complications. In
this technique instead of monitoring individual molecules the emphasis is done on
measuring the fluid mechanical properties of the blood, and that can be used as
biomarkers.”
The idea of using micro devices to model human physiology is an exciting, rapidly
growing field with huge potential for treating a wide range of health conditions.
One big application of this technique is in diagnosis and clinical monitoring. Ever
bigger is the role of these chips in Drug development.

CONCLUSION:
If the new innovative method suggested by us is applied for the purpose of
diagnosis, then the life style of the infants can be regulated and monitored. This
can lead to fewer deaths and may contribute in reducing the sufferings of people
suffering through this disease.
 BIBLIOGRAPHY:
⮚ wikipedia.org
⮚ medicineandman.com
⮚ youngscientist.org
⮚ healthyheart.com
⮚ journal-science today
A Project report on

Mend the Malign Malaria

Guided by:Submitted by:

Mrs. Pratibha Nair Gunjan BhatiaXII ‘B’
Mrs. Rimjhim JoshiAnanta Barvey XI ‘B’
Kirti Kalyani X ‘A’
Vani Tiwari IX ‘E’

QUEENS’ COLLEGE, KHANDWA ROAD, INDORE