Sickle Cell Anemia Sickle Cell
Course Instructor
Sarah Rafique
Contents
• Introduction
• Causes
• Inheritance pattern
• Signs and symptoms
• Diagnosis
• Disease Management
• Prevalence in Pakistan
2
Commonly known Types
1. Sickle Cell Trait
a. When only one gene is mutated or defected
b. Individual can live normal life until triggered massively
2. Sickle Cell Anemia/Disease
a. When both inherited genes are mutated
b. Patient will suffer the complications and life expectancy is low as compared
to trait
3
Sickle Cell Disease (SKD)
A type of hemoglobinopathies
Inherited blood disorder
Most common type is sickle cell anemia
The defect lies in quality of hemoglobin because of mutation in DNA
Problem with sickle cell anemia starts around 5-6 months of age
4
Basic Information
A serious condition in which red blood cells become
sickle-shaped
Normal red blood cells are smooth and round. They
move easily through blood vessels to carry oxygen to
all parts of the body.
Sickle-shaped cells don’t move easily through blood.
They’re stiff and sticky and tend to form clumps and
get stuck in blood vessels.
The clumps of sickle cell block blood flow in the
blood vessels that lead to the limbs and organs.
Blocked blood vessel can cause pain, serious
infection, and organ damage. 5
Inheritance Pattern of Sickle Cell
Disease
6
Sickle cell disease occurs when a person inherits two abnormal
copies of the β-globin gene (HBB) that makes hemoglobin, one
from each parent.
This gene occurs in chromosome 11.
Several subtypes exist, depending on the exact mutation in
each hemoglobin gene.
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.
7
Discovery of SCD
• Sickle cell disease (SCD) refers to a group of hemoglobinopathies that
include mutations in the gene encoding the β subunit of hemoglobin.
• In 1949, Beet described the patterns of inheritance in patients with
SCD.
• In the same year, the molecular nature of sickle hemoglobin
(HbS) was described in a paper 'Sickle Cell Anemia Hemoglobin.
• Ingram Vernon, in 1956, used a fingerprinting technique to describe
the replacement of negatively charged glutamine with neutral valine
and validated the findings of Linus Pauling.
8
Sub groups of SCD
Within the umbrella of SCD, many subgroups exist,
Namely sickle cell anemia (SCA),
hemoglobin SC disease (HbSC), and
hemoglobin sickle-beta-thalassemia (beta-thalassemia positive or beta-
thalassemia negative).
Several other minor variants within the group of SCDs also, albeit not as
common as the varieties mentioned above.
Lastly, it is essential to mention the sickle cell trait (HbAS), which carries a
heterozygous mutation and seldom presents clinical signs or symptoms.
Sickle cell anemia is the most common form of SCD, with a lifelong
affliction of hemolytic anemia requiring blood transfusions, pain crises, and
organ damage
9
Mutation At DNA Level
1. The normal gene of β globin protein
contains Glutamine (amino acid)
2. When the codon responsible to code
for glutamine is mutated the resultant
product is changed
3. The resultant amino acid is “Valine”
4. The chemical properties of both the
amino acids are different
5. Glutamine is hydrophilic while Valine is
hydrophobic amino acid
6. The solubility of Hb.S is much less than
Hb. A due to presence of valine
10
Changes at Protein Level
The amino acid change causes
polymerization of this mutant
hemoglobin (hemoglobin S
[HbS]) to form fibers upon
deoxygenation in the tissues,
the root cause of the pathology
of the disease. The fibers make
the red blood cells less flexible
and distort the shape of the
cells, a process typically
referred to as sickling
11
Changes at Cellular Level
12
Gene to Cell Changes
(Sparkenbaugh & Ramadas, 2023)
13
Sparkenbaugh, E., & Ramadas, N. (2023). The APC-EPCR-PAR1 axis in sickle cell disease. Frontiers in Medicine, 10, 1141020.
Trigger Factors of Sickle Cell Anemia
An attack can be set off by
• Temperature changes,
• Stress
• Dehydration &
• High altitude.
14
Sign & Symptoms
• Signs of sickle cell disease usually begin in early childhood.
• 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.
• Patient presents with clinical presentation of anemia like
• fatigue
• Bone pain
• Recurrent infections etc
• The peripheral blood smear shows presence of increased number of
sickle cells
15
Complications of Sickle Cell
Anemia
16
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 anemia and crises that could be of many
types, including the
• vaso-occlusive crisis, aplastic crisis, splenic sequestration
crisis, hemolytic 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.
17
Vaso-occlusive crisis
1. The vaso-occlusive crisis is caused by sickle-shaped red blood cells
that obstruct capillaries and restrict blood flow to an organ
2. Resulting in ischaemia, pain, necrosis, and often organ damage.
3. The frequency, severity, and duration of these crises vary
considerably. Painful crises are treated with hydration, analgesics,
and blood transfusion
4. Vaso-occlusive crisis involving organs such as the 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
18
Complications of Vaso-occlusive Crisis in
SCD
19
Splenic Sequestration Crisis
• Continuous destruction and narrowing of blood vessels result in
reduced function of spleen of clearing defective cells
• Splenic damage increases risk of infections via encapsulated
microorganisms
• Splenic crises is represented as acute pain and splenic enlargement
due to trapping of defected RBCs, and severe Hb. drop
• This is a condition of medical emergency, if not treated with
supportive management therapy i.e; transfusion, may result in death
within 1-2 hrs
20
Acute Chest Syndrome
• It is represented as signs or symptoms of chest pain, fever and
pulmonary infiltrate
• Second most common complication that accounts for 25% deaths in
SCD
• Mostly patients of acute vaso-occulusive crises develop chest
syndrome
21
Hemolytic Crisis
• It is accelerated due sudden drop in hemoglobin level
• The RBCs breaks at fastest rate
• It is more obvious due to oxidative stress that affects not only RBCs
but WBCs and Platelets.
• This is because of the unbalance between oxidants and anti-oxidants
due to rapid RBC destruction. The newly formed cells are not properly
oxygenated or formed
• This is managed through blood transfuions
22
Dactylitis
• Dactylitis or sausage digit is inflammation of
an entire digit (a finger or toe), and can be
painful.
• The word dactyl comes from the Greek word
"daktylos" meaning "finger". In its medical
term, it refers to both the fingers and the
toes.
• Presented at 6 months of age, may last for a
month
• It can be triggered by respiratory infection,
opiate administration and surgery
23
SCD Complications
Sr.# Complication Reason
1 Increased risk of infections Splenectomy
2 Stroke Narrowing of blood vessels
3 Choleliathiasis (gallstones) Excessive bilirubin production
4 Osteomyelitis (bacterial infection of Intravascular sickling in bowel and
bone) ischemia
5 Leg ulcers
6 Pulmonary hypertension Increased pressure in pulmonary artery
7 Cardiomyopathy Scarring or fibrosis of cardiac tissues
8 Chronic kidney failure Due to sickle cell nephropathy, protein
and blood loss in urine. Progresses to
end stage renal failure
24
Pathophysiology
• The loss of red blood cell elasticity is central to the pathophysiology.
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 ischemia.
25
Diagnosis
• Complete blood count shows Hb. Between 6-8 gm/dl
• Peripheral blood picture shows increased retic count and sickle
shaped RBCs
• Sickle cells are confirmed using sodium met bisulfide test
• Hb Electroporesis shows presence of Hb.C
26
Management of Disease
• Genetic counselling
• Counsel families about genetic testing
• Give awareness of the possible consequences
• Avoid dehydration
• Diet rich in calcium and vitamin D is recommended
• Since birth till 5 years daily use of penicillin to avoid infections due to
immature immune system
• Folic acid is also suggested
27
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.
• In Pakistan cases are being reported from Baluchistan, KPK, Sindh and
Punjab, yet no definite figure can be mentioned
28
Blessing in Disguise
• Sickle cell anemia patients can not develop malaria
29
30
