Sickle cell disease

Sickle cell disease

• Sickle cell disease affect
haemoglobin – the part of the
blood that carries oxygen
around the body
• Oxygen is carried less
efficiently around the body in
people with sickle cell disease
• Autosomal recessive
inheritance
 Definition
Sickle cell disease: is a genetic disorder that
affects erythrocytes (RBC) causing them to
become sickle or crescent shaped.
The effects of this condition due to an
abnormality of the hemoglobin molecules
found in erythrocytes.
 Red Blood
Cells

Erythropoesi
Smooth and
s
round

Squeeze
Contains
through Erythrocytes
Capillaries Hemoglobin

Transports
No Nucleus oxygen

100 – 120
days
 Hemoglobin
⚫ Each hemoglobin molecule is made up of four
heme groups surrounding a globin group.
⚫ Heme contains iron and gives a red color to the molecule.
⚫ Globin consists of two linked pairs of polypeptide chains.
Sickle cell affects quality of haemoglobin
▪ Red blood cells can take on sickle shape when
they give up oxygen in small blood vessels
▪ They become stiff and can’t circulate properly
▪ They can also become stuck in small blood
vessels and cause blockages
 Types of Sickle Cell Disease
❖ Sickle Cell disease (most severe form) two sickle
cell hemoglobin genes HbSS
❖ HbSC (milder form) One sickle cell hemoglobin
gene and one abnormal hemoglobin C gene
❖ HbS Beta Thalassemia: One sickle cell gene and
one gene for beta thalassemia (vary in severity)
❖ HbSD, HbSO, HbSO: rare and vary in severity
 Haemoglobin
Normal haemoglobin or HbA: 4 chains; 2 alpha & 2 beta
In Sickle Cell Disease: There is a substitution of the amino
acid valine for glutamic acid in the beta chain, forming what is
known as HbS
Valine is more hydrophobic than glutamic acid causing the
hemoglobin molecules to be attracted to one another, forming
long filaments that distort the shape of the red blood cells and
produce the characteristic sickling.
 Sickle Cell: Molecular Basis
• Glutamate → Valine at 6th position
beta globin chain
• Sickle Hb forms polymers when
deoxygenated
• Polymerized sickle Hb injures RBC
membrane and distorts its shape
• Distorted RBC is hemolyzed
 Genetics of SCD
The change in cell structure arises from
a change in the structure of
hemoglobin.

A single change in an amino acid

causes hemoglobin to aggregate.
Hemoglobin A Hemoglobin S
Pathophysiology of Sickle Cell Disease
HbS Polymer
Vaso-occlusio
n

Argini N
ne O
Hemolysis
 Sickle Cell: Pathophysiology
• Deoxygenation of mutant Hb leads to
• ↑ K+ efflux
• ↑ cell density / dehydration
• ↑ polymerization
• Sickled cells adhere to endothelial cells
• Endothelial factors ↑ vasoconstriction
• Blood flow ↓ promotes vaso-occlusion
• “Vicious cycle” with decreased blood flow,
hypoxemia / acidosis, increased sickling
• Some cells become irreversibly sickled
 Sickle Cell Disease
• Due to presence of recessive allele denoted by
HbS.
• Causes distortion of red blood cells into long,
thin sickles.
• Causes pain, tissue damage, and cells to
rupture prematurely.
• Carriers: have heterozygous genotypes and do
not manifest symptoms.
 Inheritance of Sickle Cell Disease
⚫ If one parent has sickle cell trait
(HbAS) and the other does not
carry the sickle hemoglobin at all
(HbAA) then none of the children
will have sickle cell anemia.

⚫ There is a one in two (50%)

chance that any given child will get
one copy of the HbAS gene and
therefore have the sickle cell trait.

⚫ It is equally likely that any given

child will get two HbAA genes and
be completely unaffected.
 Inheritance of Sickle Cell Disease
⚫ If both parents have sickle cell
trait (HbAS) there is a one in
four (25%) chance that any
given child could be born with
sickle cell anemia.

⚫ There is also a one in four

chance that any given child
could be completely unaffected.

⚫ There is a one in two (50%)

chance that any given child will
get the sickle cell trait.
 Inheritance of Sickle Cell Disease
⚫ If one parent has sickle cell
trait (HbAS) and the other has
sickle cell anemia (HbSS)
there is a one in two (50%)
chance that any given child
will get sickle cell trait and a
one in two (50%) chance that
any given child will get sickle
cell anemia.

⚫ No children will be completely

unaffected.
 Predict inheritance
• Given parents’ genotypes,
you can predict offspring’s
genotypes and phenotypes
• HbS/ HbS = homozygous
recessive results in sickle cell
anemia
• Both HbA/ HbS
(heterozygous) and HbA/
HbA (homozygous
dominant) are normal.

What are the genotypic and phenotypic ratios for this cross?
 Mother’s genotype Father’s genotype

HbA/ HbS x HbA/ HbS

HbA HbS

Genotype Ratio – 1:2:1

HbA/HbA HbA/HbS 1 HbA/HbA
HbA

Health Health (Carrier) 2 HbA/HbS

1 HbS/HbS

HbA/HbS
HbS

HbS/HbS Phenotype Ratio - 3:1

Health (Carrier)
Disease
 Complications From Sickle Cell Disease
• Sickle cells become trapped and
destroyed in the spleen causing
Splenic Sequestration brain
eyes
• Shortage of red blood cells or
heart
anemia chest

• Pain episodes kidneys

bones
• Stroke or Brain Damage
• Kidney failure
• Pneumonia or Chest Syndrome
• Increased Infections
 Splenic Sequestration
• Sudden trapping of blood within the
spleen.
• Usually occurs in infants under 2 years
of age.
• May be associated with fever, pain, and
respiratory symptoms.
• Circulatory collapse and death can occur
in less than thirty minutes.
 Kidney
• Kidney damage starts very early and
progresses throughout life causing
complications in many individuals with
sickle syndromes.
• The kidneys may not filter normally,
passing protein and/or excessive
amounts of water.
 Bone Pain
• More prolonged and constant pain can
be seen with bone infarction, sickle
arthritis, and aseptic necrosis of the
femur or humerus.
• With chronic pain, non-steroidal
anti-inflammatory medications should
be used.
• TENS units, relaxation techniques,
occupational and physical therapy
approaches may be useful in reducing
pain and maintaining a good lifestyle.
 Eye Problems
• Sickle cells can cause damage to
the blood vessels in the eye,
especially in SC disease.
• New weaker blood vessels may
form and break open and bleed.
• Early treatment with laser therapy
can prevent such bleeds.
 Strokes
• Strokes are a blockage of blood flow to a
part of the brain caused by the sickle cells.
• The symptoms include one sided
weakness, numb feelings, seizures, slurred
speech or facial weakness.
• Treatment is with chronic transfusion to
maintain the Hb S level at less than 30%
to prevent recurrences or even prevent the
first stroke.
 Anemia - Jaundice
• Anemia or a low red blood cell count, is lifelong, starting in
the first year of life.
• The average red cell life is reduced from a normal of 120 days
down to an average of 10 to 20 days in sickle cell anemia.
• This produces anemia, a high reticulocyte count, and a bone
marrow factory that is producing 3 to 4 times more red cells
than normal.
• Other problems related to the anemia are yellow eyes or
jaundice (elevated indirect bilirubin),which later in childhood
and early adult life can cause gallstones
 Hand Foot Syndrome - Dactylitis
• Sickle dactylitis is one of the
first complications in sickle cell
syndromes with the highest
incidence between ages six
months and two years.
• The sickle red cells cause
painful swelling of the hands
and feet.
• This is treated with fluids and
pain medication.
• It usually will go away in a few
days without any problems.
 Acute Chest Syndrome
• Pneumonias or infections in the lung,
and acute chest syndrome, caused by
sickling red cells blocking blood
vessels in the lung, are the most
common complications.
• Infections are treated with antibiotics
and acute chest is treated with blood
transfusions.
• It’s hard to tell the two apart so both
treatments are used
 Priapism
• Priapism is the painful erection of the penis caused by
sickling red cells.
• This complication usually has an onset at age 5 to 35.
• It often occurs as a severe episode requiring
hospitalization following multiple episodes of short
duration termed stuttering.
• Onset in the early morning a waking the patient is
common.
• Treatment includes pain relief, hydration, exchange
transfusion, and surgical shunt procedures .
 Leg ulcers
• Leg ulcers are seen in 10 to 15% of
older children and adults with sickle
cell anemia.
• They may start as a simple insect bite
or cut that will not heal.
• They are likely caused by poor
circulation to the skin.
• Treatment includes saline wet-to-dry
dressings, Unna boots ,and special
wound dressings.
• Leg elevation and use of elastic
stockings are very important to speed
healing.
 Treatments for Sickle Cell
• Penicillin (to prevent infections)
• Folic Acid (to help with producing red blood cells)
• Immunisation against infections
• For some, bone marrow transplants are an option

Also important is:

• Educate the patient and carriers about the
condition of transmission from one
generation to next generation.
• Good diet
• Guarding against common complications