1. What is Sickle Cell Disease?

Sickle cell disease (SCD) is a group of blood disorders typically inherited

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

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

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

As of 2015, about 4.4 million people have sickle cell disease, while an
additional 43 million have sickle cell trait. About 80% of sickle cell disease
cases are believed to occur in Sub-Saharan Africa. It also occurs relatively
frequently in parts of India, the Arabian Peninsula, and among people of
African origin living in other parts of the world.  In 2015, it resulted in about
114,800 deaths. The condition was first described in the medical literature by
American physician James B. Herrick in 1910.  In 1949, its genetic
transmission was determined by E. A. Beet and J. V. Neel. In 1954, the
protective effect against malaria of sickle cell trait was described.

2. History
The first modern report of sickle cell disease may have been in 1846,
where the autopsy of an executed runaway slave was discussed; the key
finding was the absence of the spleen. Reportedly, African slaves in the
United States exhibited resistance to malaria, but were prone to leg
ulcers. The abnormal characteristics of the red blood cells, which later
lent their name to the condition, was first described by Ernest E.
Irons (1877–1959), intern to Chicago cardiologist and professor of
medicine James B. Herrick (1861–1954), in 1910. Irons saw "peculiar
elongated and sickle-shaped" cells in the blood of a man named Walter
Clement Noel, a 20-year-old first-year dental student from Grenada. Noel
had been admitted to the Chicago Presbyterian Hospital in December
1904 suffering from anaemia. Noel was readmitted several times over the
next three years for "muscular rheumatism" and "bilious attacks" but
completed his studies and returned to the capital of Grenada (St.
George's) to practice dentistry. He died of pneumonia in 1916 and is
buried in the Catholic cemetery at Sauteurs in the north of Grenada.
Shortly after the report by Herrick, another case appeared in the Virginia
Medical Semi-Monthly with the same title, "Peculiar Elongated and
Sickle-Shaped Red Blood Corpuscles in a Case of Severe Anemia." This
article is based on a patient admitted to the University of
Virginia Hospital on 15 November 1910. In the later description by Verne
Mason in 1922, the name "sickle cell anemia" is first used. Childhood
problems related to sickle cells disease were not reported until the 1930s,
despite the fact that this cannot have been uncommon in African-
American populations.
Memphis physician Lemuel Diggs, a prolific researcher into sickle cell
disease, first introduced the distinction between sickle cell disease and
trait in 1933, although until 1949, the genetic characteristics had not been
elucidated by James V. Neel and E.A. Beet. 1949 was the year
when Linus Pauling described the unusual chemical behaviour of
haemoglobin S, and attributed this to an abnormality in the molecule
itself.  The actual molecular change in HbS was described in the late
1950s by Vernon Ingram. The late 1940s and early 1950s saw further
understanding in the link between malaria and sickle cell disease. In
1954, the introduction of haemoglobin electrophoresis allowed the
discovery of particular subtypes, such as HbSC disease.
Large-scale natural history studies and further intervention studies were
introduced in the 1970s and 1980s, leading to widespread use of
prophylaxis against pneumococcal infections amongst other
interventions. Bill Cosby's Emmy-winning 1972 TV movie, To All My
Friends on Shore, depicted the story of the parents of a child suffering
from sickle cell disease. The 1990s had the development of
hydroxycarbamide, and reports of cure through bone marrow
transplantation appeared in 2007.
Some old texts refer to it as drepanocytosis.
 3. Types of SCD

 HbSS

People who have this form of SCD inherit two sickle cell genes (“S”), one from
each parent. This is commonly called sickle cell anemia and is usually the most
severe form of the disease.

 HbSC

People who have this form of SCD inherit a sickle cell gene (“S”) from
one parent and from the other parent a gene for an abnormal hemoglobin
called “C”. Hemoglobin is a protein that allows red blood cells to carry
oxygen to all parts of the body. This is usually a milder form of SCD.

 HbS beta thalassemia

People who have this form of SCD inherit one sickle cell gene (“S”) from
one parent and one gene for beta thalassemia, another type of anemia,
from the other parent. There are two types of beta thalassemia: “0” and
“+”. Those with HbS beta 0-thalassemia usually have a severe form of
SCD. People with HbS beta +-thalassemia tend to have a milder form of
SCD.

**** There also are a few rare types of SCD:

HbSD, HbSE, and HbSO

People who have these forms of SCD inherit one sickle cell gene (“S”)
and one gene from an abnormal type of hemoglobin (“D”, “E”, or “O”).
Hemoglobin is a protein that allows red blood cells to carry oxygen to all
parts of the body. The severity of these rarer types of SCD varies.

4. Sickle Cell Trait (SCT)

People who have SCT inherit one sickle cell gene (“S”) from one parent and
one normal gene (“A”) from the other parent. This is called sickle cell
trait (SCT). People with SCT usually do not have any of the signs of the
disease and live a normal life, but they can pass the trait on to their
children. Additionally, there are a few, uncommon health problems that
may potentially be related to sickle cell trait.
People who inherit one sickle cell gene and one normal gene have sickle
cell trait (SCT). People with SCT usually do not have any of the symptoms
of sickle cell disease (SCD), but they can pass the trait on to their children.

5. Signs and symptoms

5.1.1 Signs

SCD is a genetic condition that is present at birth. It is inherited when a

child receives two sickle cell genes—one from each parent. The severity
of symptoms can vary from person to person. Sickle cell disease may lead
to various acute and chronic complications, several of which have a high
mortality rate.

5.1.2 Sickle cell crisis

The terms "sickle cell crisis" or "sickling crisis" may be used to describe
several independent acute conditions occurring in patients with SCD,
which results in anaemia and crises that could be of many types,
including the vaso-occlusive crisis, aplastic crisis, splenic sequestration
crisis, haemolytic crisis, and others. Most episodes of sickle cell crises
last between five and seven days. "Although infection, dehydration,
and acidosis (all of which favor sickling) can act as triggers, in most
instances, no predisposing cause is identified."
5.1.3 Vaso-occlusive crisis

The vaso-occlusive crisis is caused by sickle-shaped red blood cells that

obstruct capillaries and restrict blood flow to an organ, resulting
in ischaemia, pain, necrosis, and often organ damage. The frequency,
severity, and duration of these crises vary considerably. Painful crises are
treated with hydration, analgesics, and blood transfusion; pain
management requires opioid drug administration at regular intervals until
the crisis has settled. For milder crises, a subgroup of patients manages
on nonsteroidal anti-inflammatory drugs such as diclofenac or naproxen.
For more severe crises, most patients require inpatient management for
intravenous opioids; patient-controlled analgesia devices are commonly
used in this setting. Vaso-occlusive crisis involving organs such as the
penis or lungs are considered an emergency and treated with red blood
cell transfusions. Incentive spirometry, a technique to encourage deep
breathing to minimise the development of atelectasis, is recommended.
5.1.4 Splenic sequestration crisis

The spleen is frequently affected in sickle cell disease, as the sickle-

shaped red blood cells causes narrowing of blood vessels and reduced
function in clearing the defective cells. It is usually infarcted before the
end of childhood in individuals suffering from sickle cell anaemia.
This spleen damage increases the risk of infection from encapsulated
organisms; preventive antibiotics and vaccinations are recommended for
those lacking proper spleen function.
Splenic sequestration crises are acute, painful enlargements of the spleen,
caused by intrasplenic trapping of red cells and resulting in a precipitous
fall in haemoglobin levels with the potential for hypovolemic shock.
Sequestration crises are considered an emergency. If not treated, patients
may die within 1–2 hours due to circulatory failure. Management is
supportive, sometimes with blood transfusion. These crises are transient;
they continue for 3–4 hours and may last for one day.
5.1.5 Acute chest syndrome

Acute chest syndrome is defined by at least two of these signs or

symptoms: chest pain, fever, pulmonary infiltrate or focal abnormality,
respiratory symptoms, or hypoxemia. It is the second-most common
complication and it accounts for about 25% of deaths in patients with
SCD. Most cases present with vaso-occlusive crises, and then develop
acute chest syndrome. Nevertheless, about 80% of people have vaso-
occlusive crises during acute chest syndrome.
5.1.6 Aplastic crisis

Aplastic crises are acute worsenings of the patient's baseline anaemia,

producing pale appearance, fast heart rate, and fatigue. This crisis is
normally triggered by parvovirus B19, which directly affects production
of red blood cells by invading the red cell precursors and multiplying in
and destroying them. Parvovirus infection almost completely prevents red
blood cell production for two to three days. In normal individuals, this is
of little consequence, but the shortened red cell life of SCD patients
results in an abrupt, life-threatening situation. Reticulocyte counts drop
dramatically during the disease (causing reticulocytopenia), and the rapid
turnover of red cells leads to the drop in haemoglobin. This crisis takes 4
to 7 days to disappear. Most patients can be managed supportively; some
need a blood transfusion.
5.1.7 Haemolytic crisis
Haemolytic crises are acute accelerated drops in haemoglobin level. The
red blood cells break down at a faster rate. This is particularly common in
people with coexistent G6PD deficiency. Management is supportive,
sometimes with blood transfusions.
5.1.8 Other

One of the earliest clinical manifestations is dactylitis, presenting as early

as six months of age, and may occur in children with sickle cell trait. The
crisis can last up to a month. Given that pneumonia and sickling in the
lung can both produce symptoms of acute chest syndrome, the patient is
treated for both conditions. It can be triggered by painful crisis,
respiratory infection, bone-marrow embolisation, or possibly by
atelectasis, opiate administration, or surgery. Hematopoietic ulcers may
also occur.

5.2 Symptons

Sickle cell anaemia can lead to various complications, including:

 Increased risk of severe bacterial infections is due to loss of

functioning spleen tissue (and comparable to the risk of infections
after having the spleen removed surgically). These infections are
typically caused by encapsulated organisms such as Streptococcus
pneumoniae and Haemophilus influenzae. Daily penicillin prophylaxis
is the most commonly used treatment during childhood, with some
haematologists continuing treatment indefinitely. Patients benefit
today from routine vaccination for S. pneumoniae.
 Stroke, which can result from a progressive narrowing of blood
vessels, prevents oxygen from reaching the brain. Cerebral infarction
occurs in children and cerebral haemorrhage in adults.[citation
needed]
 Silent stroke 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.
 Cholelithiasis (gallstones) and cholecystitis may result from
excessive bilirubin production and precipitation due to
prolonged haemolysis.
 Avascular necrosis (aseptic bone necrosis) of the hip and other
major joints may occur as a result of ischaemia.
 Decreased immune reactions due to hyposplenism (malfunctioning
of the spleen)
 Priapism and infarction of the penis
 Osteomyelitis (bacterial bone infection), the most common cause
of osteomyelitis in SCD is Salmonella (especially the atypical
serotypes Salmonella typhimurium, Salmonella enteritidis, Salmonella
choleraesuis, and Salmonella paratyphi B), followed
by Staphylococcus aureus and Gram-negative enteric bacilli perhaps
because intravascular sickling of the bowel leads to patchy ischaemic
infarction.
 Acute papillary necrosis in the kidneys
 Leg ulcers
 In eyes, background retinopathy, proliferative retinopathy, vitreous
haemorrhages, and retinal detachments can result in blindness. Regular
annual eye checks are recommended.
 During pregnancy, intrauterine growth restriction,
spontaneous abortion, and pre-eclampsia
 Chronic pain: Even in the absence of acute vaso-occlusive pain,
many patients have unreported chronic pain.
 Pulmonary hypertension (increased pressure on the pulmonary
artery) can lead to strain on the right ventricle and a risk of heart
failure; typical symptoms are shortness of breath, decreased exercise
tolerance, and episodes of syncope.  21% of children and 30% of
adults have evidence of pulmonary hypertension when tested; this is
associated with reduced walking distance and increased mortality.
 Cardiomyopathy and left ventricular diastolic dysfunction caused
by fibrosis or scarring of cardiac tissues. This also contributes to
pulmonary hypertension, decreased exercise capacity,
and arrhythmias.
 Chronic kidney failure due to sickle-cell nephropathy manifests
itself with hypertension, protein loss in the urine, loss of red blood
cells in urine and worsened anaemia. If it progresses to end-
stage kidney failure, it carries a poor prognosis.

6. Pathophysiology
The loss of red blood cell elasticity is central to the pathophysiology of
sickle cell disease. Normal red blood cells are quite elastic and have a
biconcave disc shape, which allows the cells to deform to pass through
capillaries. In sickle cell disease, low oxygen tension promotes red blood
cell sickling and repeated episodes of sickling damage the cell membrane
and decrease the cell's elasticity. These cells fail to return to normal shape
when normal oxygen tension is restored. As a consequence, these rigid
blood cells are unable to deform as they pass through narrow capillaries,
leading to vessel occlusion and ischaemia.
The actual anaemia of the illness is caused by haemolysis, the destruction
of the red cells, because of their shape. Although the bone
marrow attempts to compensate by creating new red cells, it does not
match the rate of destruction. Healthy red blood cells typically function
for 90–120 days, but sickled cells only last 10–20 days.
7. Management
Treatment involves a number of measures. While it has been historically
recommended that people with sickle cell disease avoid exercise, regular
exercise may benefit people. Dehydration should be avoided.A diet high
in calcium is recommended but the effectiveness of vitamin
D supplementation remains uncertain.L-glutamine use was supported by
the FDA starting at the age of five, as it decreases complications.
 Folic acid and penicillin

From birth to five years of age, penicillin daily, due to the immature

immune system that makes them more prone to early childhood illnesses,
is recommended. Dietary supplementation of folic acid had been
previously recommended by the WHO. A 2016 Cochrane review of its
use found "the effect of supplementation on anaemia and any symptoms
of anaemia remains unclear" due to a lack of medical evidence.
 Malaria prevention

The protective effect of sickle cell trait does not apply to people with
sickle cell disease; in fact, they are more vulnerable to malaria, since the
most common cause of painful crises in malarial countries is infection
with malaria. People with sickle cell disease living in malarial countries
should receive lifelong medication for prevention.

 Vaso-occlusive crisis

Most people with sickle cell disease have intensely painful episodes
called vaso-occlusive crises. However, the frequency, severity, and
duration of these crises vary tremendously. Painful crises are treated
symptomatically with pain medications; pain management requires opioid
drug administration at regular intervals until the crisis has settled. For
milder crises, a subgroup of patients manages on NSAIDs (such
as diclofenac or naproxen). For more severe crises, most patients require
inpatient management for intravenous opioids.
Extra fluids, administered either orally or intravenously, are a routine part
of treatment of vaso-occlusive crises but the evidence about the most
effective route, amount and type of fluid replacement remains uncertain.
Crizanlizumab, a monoclonal antibody target towards p-selectin was
approved in 2019 in the United States to reduce the frequency of vaso-
occlusive crisis in those 16 years and older.
 Stroke prevention

Transcranial Doppler ultrasound (TCD) can detect children with sickle

cell that have a high risk for stroke. The ultrasound test detects blood
vessels partially obstructed by sickle cells by measuring the rate of blood
into the brain, as blood flow velocity is inversely related to arterial
diameter, and consequently, high blood-flow velocity is correlated with
narrowing of the arteries. In 2002 the National Institute of Health (NIH)
issued a statement recommending that children with sickle cell get the
Transcranial Doppler ultrasound screen annually, and in 2014 a panel of
experts convened by the NIH issued guidelines reiterating the same
recommendation. One review of medical records, by hematologist Dr.
Julie Kanter at the University of Alabama at Birmingham, showed that on
average only 48.4 percent of children with sickle cell get the
recommended ultrasound test. 
A 1994 NIH study showed that children at risk for strokes who received
blood transfusions had an annual stroke rate of less than 1 percent,
whereas those children who did not receive blood transfusions had a 10
percent stroke rate per year. (Also see 1998 study in the New England
Journal of Medicine.) In addition to ultrasounds and blood transfusions,
the inexpensive generic drug hydroxyurea can reduce the risk of
irreversible organ and brain damage. Guidelines from NIH published in
2014 state that all children and adolescents should take hydroxyurea, as
should adults with serious complications or three or more pain crises in a
year. 
 Acute chest syndrome

Management is similar to vaso-occlusive crisis, with the addition of

antibiotics (usually a quinolone or macrolide, since cell wall-deficient
["atypical"] bacteria are thought to contribute to the syndrome),
[93] oxygen supplementation for hypoxia, and close observation. In the
absence of high quality evidence regarding the effectiveness of antibiotics
for acute chest syndrome in people with sickle cell disease, there is no
standard antibiotic treatment as of 2019.[94] It is recommended that
people with suspected acute chest syndrome should be admitted to the
hospital with worsening A-a gradient an indication for ICU admission.
Should the pulmonary infiltrate worsen or the oxygen requirements
increase, simple blood transfusion or exchange transfusion is indicated.
The latter involves the exchange of a significant portion of the person's
red cell mass for normal red cells, which decreases the level of
haemoglobin S in the patient's blood. However, there is currently
uncertain evidence about the possible benefits or harms of blood
transfusion for acute chest syndrome in people with sickle cell disease.
 Hydroxyurea

Hydroxyurea, also known as hydroxycarbamide, probably reduces the

frequency of painful episodes and the risk of life-threatening illness or
death but there is currently insufficient evidence regarding the risk of
adverse effects. Hydroxyurea and phlebotomy combined may be more
effective than transfusion and chelation combined in terms of pain, life-
threatening illness and risk of death.
It was the first approved drug for the treatment of sickle cell anaemia, and
was shown to decrease the number and severity of attacks in 1995 and
shown to possibly increase survival time in a study in 2003. This is
achieved, in part, by reactivating fetal haemoglobin production in place of
the haemoglobin S that causes sickle cell anaemia. Hydroxyurea had
previously been used as a chemotherapy agent, and some concern exists
that long-term use may be harmful, but this risk is either absent or very
small and the benefits likely outweigh the risks.
Voxelotor was approved in the United States in 2019 to increase
hemoglobin in people with SS disease.
 Blood transfusion

Blood transfusions are often used in the management of sickle cell

disease in acute cases and to prevent complications by decreasing the
number of red blood cells (RBCs) that can sickle by adding normal red
blood cells. In children, preventive RBC transfusion therapy has been
shown to reduce the risk of first stroke or silent stroke when transcranial
Doppler ultrasonography shows abnormal cerebral blood flow. In those
who have sustained a prior stroke event, it also reduces the risk of
recurrent stroke and additional silent strokes.
 Bone marrow transplant

Bone marrow transplants have proven effective in children; they are the

only known cure for SCD. However, bone marrow transplants are
difficult to obtain because of the specific HLA typing necessary. Ideally,
a close relative (allogeneic) would donate the bone marrow necessary for
transplantation. Some gene therapies are under development that would
alter the patient's own bone marrow stem cells ex vivo, which can then be
transplanted back into the patient after chemotherapy eliminates the
original unmodified cells.
 Avascular necrosis

When treating avascular necrosis of the bone in people with sickle cell
disease, the aim of treatment is to reduce or stop the pain and
maintain joint mobility. Current treatment options include resting the
joint, physical therapy, pain-relief medicine, joint-replacement surgery,
or bone grafting. High quality, randomized, controlled trials are needed to
assess the most effective treatment option and determine if a combination
of physical therapy and surgery is more effective than physical therapy
alone.
 Psychological therapies

Psychological therapies such as patient education, cognitive

therapy, behavioural therapy, and psychodynamic psychotherapy, that
aim to complement current medical treatments, require further research to
determine their effectiveness.
8. Prognosis
About 90% of people survive to age 20, and close to 50% survive
beyond age 50. In 2001, according to one study performed in Jamaica,
the estimated mean survival for people was 53 years for men and 58
years for women with homozygous SCD. The specific life expectancy in
much of the developing world is unknown. In 1975 about 7.3% of
people with SCD died before their 23rd birthday; while in 1989 2.6% of
people with SCD died by the age of 20.

9. Epidemiology
The highest frequency of sickle cell disease is found in tropical regions,
particularly sub-Saharan Africa, tribal regions of India, and the Middle
East. Migration of substantial populations from these high-prevalence
areas to low-prevalence countries in Europe has dramatically increased in
recent decades and in some European countries, sickle cell disease has
now overtaken more familiar genetic conditions such
as haemophilia and cystic fibrosis. In 2015, it resulted in about 114,800
deaths.
Sickle cell disease occurs more commonly among people whose
ancestors lived in tropical and subtropical sub-Saharan regions where
malaria is or was common. Where malaria is common, carrying a single
sickle cell allele (trait) confers a heterozygote advantage; humans with
one of the two alleles of sickle cell disease show less severe symptoms
when infected with malaria.
This condition is inherited in an autosomal recessive pattern, which
means both copies of the gene in each cell have mutations. The parents
each carry one copy of the mutated gene, but they typically do not show
signs and symptoms of the condition.
 Africa

Three-quarters of sickle cell cases occur in Africa. A recent WHO report

estimated that around 2% of newborns in Nigeria were affected by sickle
cell anaemia, giving a total of 150,000 affected children born every year
in Nigeria alone. The carrier frequency ranges between 10 and 40%
across equatorial Africa, decreasing to 1–2% on the North African coast
and <1% in South Africa. Studies in Africa show a significant decrease in
infant mortality rate, ages 2–16 months, because of the sickle cell trait.
This happened in areas of predominant malarial cases.
Uganda has the fifth-highest sickle cell disease burden in Africa. One
study indicates that 20 000 babies per year are born with sickle cell
disease with the sickle cell trait at 13·3% and with disease 0·7%.
 United States

The number of people with the disease in the United States is about one
in 5,000, mostly affecting Americans of sub-Saharan African descent. In
the United States, about one out of 365 African-American children and
one in every 16,300 Hispanic-American children have sickle cell
anaemia. An estimated 100 thousand Americans have the disease. The
life expectancy for men with SCD is approximately 42 years of age while
women live approximately six years longer. An additional 2 million are
carriers of the sickle cell trait. Most infants with SCD born in the United
States are identified by routine neonatal screening. As of 2016 all 50
states include screening for sickle cell disease as part of their newborn
screen. The newborn's blood is sampled through a heel-prick and is sent
to a lab for testing. The baby must have been eating for a minimum of 24
hours before the heel-prick test can be done. Some states also require a
second blood test to be done when the baby is two weeks old to ensure
the results. Sickle cell anemia is the most common genetic disorder
among African Americans. Approximately 8% are carriers and 1 in 375
are born with the disease. Patient advocates for sickle cell disease have
complained that it gets less government and private research funding than
similar rare diseases such as cystic fibrosis, with researcher Elliott
Vichinsky saying this shows racial discrimination or the role of wealth in
health care advocacy.
 France

As a result of population growth in African-Caribbean regions

of overseas France and immigration from North and sub-Saharan Africa
to mainland France, sickle cell disease has become a major health
problem in France. SCD has become the most common genetic disease in
the country, with an overall birth prevalence of one in 2,415
in metropolitan France, ahead of phenylketonuria (one in 10,862),
congenital hypothyroidism (one in 3,132), congenital adrenal
hyperplasia (one in 19,008) and cystic fibrosis (one in 5,014) for the same
reference period.
Since 2000, neonatal screening of SCD has been performed at the
national level for all newborns defined as being "at-risk" for SCD based
on ethnic origin (defined as those born to parents originating from sub-
Saharan Africa, North Africa, the Mediterranean area (South
Italy, Greece, and Turkey), the Arabic peninsula, the French overseas
islands, and the Indian subcontinent).
 United Kingdom

In the United Kingdom, between 12,000 and 15,000 people are thought to
have sickle cell disease with an estimated 250,000 carriers of the
condition in England alone. As the number of carriers is only estimated,
all newborn babies in the UK receive a routine blood test to screen for the
condition. Due to many adults in high-risk groups not knowing if they are
carriers, pregnant women and both partners in a couple are offered
screening so they can get counselling if they have the sickle cell trait. In
addition, blood donors from those in high-risk groups are also screened to
confirm whether they are carriers and whether their blood filters
properly. Donors who are found to be carriers are then informed and their
blood, while often used for those of the same ethnic group, is not used for
those with sickle cell disease who require a blood transfusion.
 Middle East

In Saudi Arabia, about 4.2% of the population carry the sickle cell trait
and 0.26% have sickle cell disease. The highest prevalence is in the
Eastern province, where approximately 17% of the population carry the
gene and 1.2% have sickle cell disease. In 2005, Saudi Arabia introduced
a mandatory premarital test including HB electrophoresis, which aimed to
decrease the incidence of SCD and thalassemia.
In Bahrain, a study published in 1998 that covered about 56,000 people in
hospitals in Bahrain found that 2% of newborns have sickle cell disease,
18% of the surveyed people have the sickle cell trait, and 24% were
carriers of the gene mutation causing the disease. The country began
screening of all pregnant women in 1992 and newborns started being
tested if the mother was a carrier. In 2004, a law was passed requiring
couples planning to marry to undergo free premarital counseling. These
programs were accompanied by public education campaigns.
 India and Nepal

Sickle cell disease is common in some ethnic groups of central India,

[137] where the prevalence has ranged from 9.4 to 22.2% in endemic
areas of Madhya Pradesh, Rajasthan, and Chhattisgarh.[138] It is also
endemic among Tharu people of Nepal and India; however, they have a
sevenfold lower rate of malaria despite living in a malaria infested zone.
 Caribbean Islands

In Jamaica, 10% of the population carry the sickle cell gene, making it
the most prevalent genetic disorder in the country.
10. Society and culture
U.S. Social Security

Effective 15 September 2017, the U.S. Social Security

Administration issued a Policy Interpretation Ruling providing
background information on sickle cell disease and a description of
how Social Security evaluates the disease during its adjudication process
for disability claims.
Stigma in the U.S.
In the U.S., there are stigmas surrounding SCD that discourage people
with SCD from receiving necessary care. These stigmas mainly affect
people of African American and Latin ancestries, according to the
National Heart, Lung, and Blood Institute. People with SCD experience
the impact of stigmas of the disease on multiple aspects of life including
social and psychological well being. Studies have shown that those with
SCD frequently feel as though they must keep their diagnosis a secret to
avoid discrimination in the workplace and also among peers in
relationships. In the 1960s, the US government supported initiatives for
workplace screening for genetic diseases in an attempt to be protective
towards people with SCD. By having this screening, it was intended that
employees would not be placed in environments that could potentially be
harmful and trigger SCD.
Stigma in Uganda[
Uganda has the 5th highest sickle cell disease (SCD) burden in the world.
In Uganda, social stigma exists for those with sickle cell disease because
of the lack of general knowledge of the disease. The general gap in
knowledge surrounding sickle cell disease is noted among adolescents
and young adults due to the culturally sanctioned secrecy about the
disease. While most people have heard generally about the disease, a
large portion of the population is relatively misinformed about how SCD
is diagnosed or inherited. Those who are informed about the disease
learned about it from family or friends and not from health professionals.
Failure to provide the public with information about sickle cell disease
results in a population with a poor understanding of the causes of the
disease, symptoms, and prevention techniques. The differences,
physically and socially, that arise in those with sickle cell disease, such as
jaundice, stunted physical growth, and delayed sexual maturity, can also
lead them to become targets of bullying, rejection, and stigma.
Rate of sickle cell disease in Uganda

The data compiled on sickle cell disease in Uganda has not been updated
since the early 1970s. The deficiency of data is due to a lack of
government research funds, even though Ugandans die daily from
SCD. Data shows that the trait frequency of sickle cell disease is 20% of
the population in Uganda. This means that 66 million people are at risk of
having a child who has sickle cell disease. It is also estimated that about
25,000 Ugandans are born each year with SCD and 80% of those people
don't live past five years old. SCD also contributes 25% to the child
mortality rate in Uganda. The Bamba people of Uganda, located in the
southwest of the country, carry 45% of the gene which is the highest trait
frequency recorded in the world. The Sickle Cell Clinic in Mulago is only
one sickle cell disease clinic in the country and on average sees 200
patients a day.
Misconceptions about sickle cell disease

The stigma around the disease is particularly bad in regions of the country
that are not as affected. For example, Eastern Ugandans tend to be more
knowledgable of the disease than Western Ugandans, who are more likely
to believe that sickle cell disease resulted as a punishment
from God or witchcraft. Other misconceptions about SCD include the
belief that it is caused by environmental factors but, in reality, SCD is a
genetic disease. There have been efforts throughout Uganda to address
the social misconceptions about the disease. In 2013, the Uganda Sickle
Cell Rescue Foundation was established to spread awareness of sickle
cell disease and combat the social stigma attached to the disease. In
addition to this organization's efforts, there is a need for the inclusion of
sickle cell disease education in preexisting community health
education programs in order to reduce the stigmatization of sickle cell
disease in Uganda.
Social isolation of people with sickle cell disease
The deeply rooted stigma of SCD from society causes families to often
hide their family members' sick status for fear of being labeled, cursed, or
left out of social events. Sometimes in Uganda, when it is confirmed that
a family member has sickle cell disease, intimate relationships with all
members of the family are avoided. The stigmatization and social
isolation people with sickle cell disease tend to experience is often the
consequence of popular misconceptions that people with SCD should not
socialize with those free from the disease. This mentality robs people
with SCD of the right to freely participate in community activities like
everyone else SCD-related stigma and social isolation in schools,
especially, can make a life for young people living with sickle cell
disease extremely difficult. For school-aged children living with SCD, the
stigma they face can lead to peer rejection. Peer rejection involves the
exclusion from social groups or gatherings. It often leads the excluded
individual to experience emotional distress and may result in their
academic underperformance, avoidance of school, and occupational
failure later in life. This social isolation is also likely to negatively impact
people with SCD's self-esteem and overall quality of life.