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Autosomal recessive (or co-dominant) genetic disease result from sub situation of
valine by glutamic acid at position 6 of beta-globin gene leading to production
of defective for of Hb (Hbss).
Can be define as hemolytic anemia with hemoglobinopathy
Characterized by sever chronic hemolysis, crisis and short life expectancy
Affected children present with pallor, fever, jaundice, hand & foot pain, bone
pain, fatigability, splenomegaly
Diagnosis starts with screening by solubility test and sickling test then confirmed
by hemoglobin zone electrophoresis.
Sickle-cell disease (SCD), or sickle-cell anemia (or anemia, SCA) or
drepanocytosis, is an autosomal recessive genetic blood disorder with over
dominance, characterized by RBCs that abnormal, rigid, sickle shape.
Sickling decreases the cells' flexibility and results in a risk of various
Sickling occurs because of a mutation in the hemoglobin gene.
Life expectancy is shortened.
Sickle-cell disease, most commonly occurs in tropical and sub-tropical regions
where malaria is or was common.
Sickle-cell anemia is the name of a specific form of sickle-cell disease in which
1. homozygosity for the mutation that causes HbS. Sickle-cell anemia is also
referred to as "HbSS", "SS disease", "haemoglobin S" or permutations thereof.
2. heterozygous people, who have only one sickle gene and one normal adult
haemoglobin gene, it is referred to as "HbAS" or "sickle cell trait".
3. Other, rarer forms of sickle-cell disease include sickle-haemoglobin
C disease (HbSC), sickle beta-plus-thalassaemia (HbS/β+
) and sickle beta-
Compound heterozygous states sickle-cell disease
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In which the person has only one copy of the mutation that causes HbS and one
copy of another abnormal haemoglobin allele.
Pathological condition leads to death and severe complications.
Not all inherited variants of haemoglobin are detrimental, a concept known
as genetic polymorphism.
Signs and symptoms
Sickle-cell disease may lead to various acute and chronic complications, several
of which have a high mortality rate.
Sickle cell crisis
Used to describe several independent acute conditions occurring in patients with
sickle cell disease.
Types of crisis
1. vaso-occlusive crisis
2. aplastic crisis
3. sequestration crisis
4. hemolytic crisis
Most episodes of sickle cell crises last between five and seven days.
1. Vaso-Occlusive Crisis
The vaso-occlusive crisis is caused by sickle-shaped red blood cells obstruct
capillaries and restrict blood flow to an organ, resulting
in ischemia, pain, necrosis and often organ damage.
Painful crises are treated with hydration, analgesics, and blood transfusion;
Vaso-occlusive crisis involving organs such as the penis or
2. Splenic Sequestration Crisis
Autosplenectomy increases the risk of infection from encapsulated organisms;
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Splenic sequestration crises: are acute, painful enlargements of the spleen lead
If not treated, patients may die within 1–2 hours due to circulatory failure.
Management is supportive with blood transfusion.
These crises are transient continue for 3–4 hours and may last for one day.
3. Aplastic Crisis
Acute worsenings of the patient's baseline anemia,
Producing pallor, tachycardia, and fatigue.
Triggered by parvovirus B19, which directly affects erythropoiesis by invading
the red cell precursors and multiplying in them and destroying them.
This crisis takes 4 days to one week to disappear.
Can be managed supportively need blood transfusion.
4. Hemolytic Crisis
Hemolytic crises are acute accelerated drops in haemoglobin level.
RBCs break down at a faster rate.
Common in patients with co-existent G6PD deficiency.
I. Dactylitis, presenting as early as six months of age, and may occur in
children with sickle trait.
II. Acute chest syndrome, a condition characterized by fever, chest pain,
difficulty breathing, and pulmonary infiltrate on a chest X-ray.
Sickle-cell anemia can lead to various complications, including:
1. Overwhelming Post-(Auto)Splenectomy Infection (Opsi),
Caused by encapsulated organisms such as Streptococcus
pneumoniae andHaemophilus influenzae.
Treated by penicillin prophylaxis
Caused due to progressive narrowing of blood vessels, preventing oxygen
from reaching the brain.
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Cerebral infarction occurs in children and cerebral haemorrhage in adults.
3. Silent Stroke
Associated with damage to the brain.
4. Avascular necrosis (aseptic bone necrosis)
Of the hip and joints occur as a result of ischemia.
5. Decreased immune reactions due to hyposplenism
(malfunctioning of the spleen).
6. Priapism and infarction of the penis.
7. Osteomyelitis (bacterial bone infection);
The most common cause of osteomyelitis in sickle cell disease is Salmonella
8-Opioid tolerance, which can occur as a normal, physiologic response to the
therapeutic use of opiates. Addiction to opiates occurs no more commonly among
individuals with sickle-cell disease than among other individuals treated with
opiates for other reasons.
8. Acute papillary necrosis in the kidneys.
9. Leg ulcers.
10. During pregnancy, intrauterine growth retardation, spontaneousabortion,
11. Chronic pain
12. Pulmonary hypertension (increased pressure on the pulmonary artery),
13. Chronic renal failure due to Sickle cell nephropathy—manifests itself
(High blood pressure), proteinuria (protein loss in the, .urine), hematuria (loss of
red blood cells in urine) and worsened anemia. If it progresses to end-stage renal
15-CHOLELITHIASIS (gallstones) and CHOLECYSTITIS,
Result from excessive bilirubin production and precipitation due to
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The heterozygous form (sickle cell trait) is always asymptomatic,
Sickle-cell anemia is caused by a point mutation in the β-globin chain of
haemoglobin, causing the amino acid glutamic acid to be replaced with the
hydrophobic amino acid valine at the sixth position. The β-globin gene is found
chromosome11. The association of two wild-type α-globin subunits with two
mutant β-globin subunits forms haemoglobin S (HbS). Under low-oxygen
conditions the absence of a polar amino acid promotes the non-covalent
polymerization (aggregation) of haemoglobin, which distorts red blood cells into
a sickle shape and decreases their elasticity in center of RBC
Normal red blood cells are quite elastic, 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
decreases 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.
The actual anemia of the illness is caused by hemolysis, the destruction of the red
cells inside the spleen, because of their misshape. 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 live 90-120 days, but sickle
cells only survive 10–20 days.
Sickle-cell conditions are inherited from parents in much the same way as
blood type, hair color and texture, eye color, and other physical traits.
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The types of haemoglobin a person makes in the red blood cells depend on
what haemoglobin genes are inherited from his parents.
1. If one parent has sickle-cell anemia (SS) and the other has sickle-cell trait
(AS), there is a 50% chance of a child's having sickle-cell disease (SS) and a
50% chance of a child's having sickle-cell trait (AS).
2. When both parents have sickle-cell trait (AS), a child has a 25% chance
(1 of 4) of sickle-cell disease (SS), as shown in the diagram.
1. Folic acid and penicillin
2. Malaria chemoprophylaxis
3. Vaso-occlusive crisis
Diclofenac or naproxen
4. Acute chest crisis
Antibiotics (usually a quinolone or macrolide)
Oxygen supplementation for hypoxia
6. Transfusion therapy
7. Bone marrow transplants
Bone marrow transplants have proven to be effective in children.
Sub-Saharan Africa, India and the Middle-East.