SICKLE CELL ANEMIA

DR.PETER MASASI
DEFINITION

• Sickle cell disease is a genetic disorder that

affects red blood cells causing them to
become sickled or crescent shaped.

• The effects of this condition is due to the

abnormality of the hemoglobin molecules
found in red blood cells
HEMOGLOBIN

• The oxygen carrying pigment and predominant

protein in the red blood cells

• Hb forms an unstable reversible bond with

oxygen

• Oxyhemoglobin: oxygenated

• Deoxyhemoglobin : reduced
HEMOGLOBIN

• Each Hb molecule is made up of four heme

groups surrounding a globin group
• Heme contains iron and gives red color to the
molecule
• Globin consists of two linked pairs of
polypeptide chains
 GENETICS OF SCD

• SCD is Hb disorders results from the inheritance of

sickle β-globin gene

• Substitution of valine for glutamic acid aa in the

position 6 of β globin chain (GAG→GTG)

• The homozygous state(HbSS or sickle cell anaemia) is

the most common form of SCD
GENETICS OF SCD
INHERITANCE:
 EPIDEMIOLOGY
• High Prevalence: Sub-Saharan Africa, The
Mediterranean basin, The Middle East & India.

• Highest burden: In Africa

• 75% of the 300,000 global births of SCD per year
• Childhood mortality remains high (50 and 90%)

• Tanzania: Amongst top 5 countries in the world with

the highest estimated No. of new-borns (11,000/yr)
• Most affected regions: Eastern coast and North west
Region around lake Victoria.
PATHOPHYSIOLOGY OF SCA
PATHOPHYSIOLOGY OF SCA..

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 1. VASO-OCCLUSIVE CRISES: PAINFUL CRISIS

• Most frequent.

• Triggers: Infection, acidosis,

dehydration or deoxygenation

• Infarcts causing severe pain

occur in the bones

• Hips, Shoulders and

Vertebrae are commonly
affected
1. VASO-OCCLUSIVE CRISES: VISCERAL CRISIS

• Infarction and pooling of blood, often with a severe

exacerbation of anaemia.

A. The acute sickle chest syndrome

• New pulmonary infiltrate, presenting with chest pain,

dyspnoea,↓SO2

• Most common cause of death both in children and adults.

 1. VASO-OCCLUSIVE CRISES: VISCERAL CRISIS..
B. Hepatic Sequestration
• Hepatic sequestration
• Intrahepatic cholestasis
• Transfusion-acquired infection
• Transfusional haemosiderosis.

C. Splenic sequestration
• Typically seen in infants
• Presents with splenomegaly, ↓Hb and abdominal
pain.
 1. VASO-OCCLUSIVE CRISES: VISCERAL CRISIS..
D. Autosplenectomy

• Splenomegaly occurs in infancy and early childhood but

later often ↓size as a result of infarcts.

• Continued splenic dysfunction eventually leads to

infarction and loss of splenic function
• Predisposing to infection by encapsulated organisms
 2. APLASTIC CRISIS
• Occur as a result of infection with parvovirus or from FA
deficiency
• Characterized by a sudden ↓Hb and reticulocytes,
• usually requiring transfusion.

Stroke- one of the leading cause of death.

-can be ischemic, haemorrhagic stroke,
TIA, cerebral venous thrombosis.
 3. STROKE
• One of the leading cause of death.

• Can be:
• Ischemic stroke
• Haemorrhagic stroke
• TIA
• cerebral venous thrombosis.
 4. HAEMOLYTIC CRISIS
• Increase hemolysis→ ↓ Hb, ↑ Retics count

• Usually accompanied by painful crisis

• Sickle RBCs are mechanically weak and are prone to

intravascular haemolysis
• However the leading mechanism is extravascular hemolysis
by RES

• The life time of sickle RBCs ranges 10-20 days

DIAGNOSIS OF SCA
• Hx and Physical examination
• Sx of anaemia, pain, difficult in breathing
• O/E: Pale, Jaundice, boozing of the skull,LL
oedema

• Systemic examination:
• CNS, CVS, RS, PA, GU, MSS
 LAB INVESTIGATIONS
Screening tests
• Sickling test
• Solubility test

• PBS
• Sickle cells and target cells
CONFIRMATORY TESTS
• Hb electrophoresis
• Isoelectric focusing
• HPLC to determine percentages of HbS, HbF
and HbA

Genetic studies: PCR

OTHER INVESTIGATIONS:
• CBC, Retics count
• Chest x-ray, blood gas
• Liver enzymes, abdominal ultrasound.
• LDH, Creatinine and urea
• Consider X-ray of extremities
• Head CT if neurological changes
• Newborn screen
 MANAGEMENT:
• Avoid precipitants

• Folic acid

• Good general nutrition and hygiene.

• Vaccination :Pneumococcal, Haemophilus and meningococcal

vaccination

• Hepatitis B vaccination is also given as transfusions may be needed.

• Crises: Rest, warmth, Rehydration by oral fluids and/or intravenous

normal saline, analgesics
 MANAGEMENT..
• Gene therapy

• HSCT

• Hydroxyurea
• Reactivates Fetal Hb production
• ↓severity of attacks
• ↑life span

• Chronic Transfusion Therapy

TRANSFUSION IN SCA
• Transfusion ↑ the risk of Fe overload and
allo-immunization

• Indicated when there is evidence benefit of

reduced morbidity and mortality
• Stroke, ACS, Severe painful crises, Symptomatic
anemia, Perioperative
 SICKLE CELL TRAIT (HBAS)
• Benign condition that has no haematological
manifestations

• Associated with Normal growth and life expectancy.

• The ratio of HbA to HbS is 60:40, owing to the greater

affinity of α-globin chains for βA-globin chains.

• Sickling and vaso-occlusion under extreme

circumstances can lead to Rhabdomyolysis, Acute Renal
Failure and Cardiac arrhythmias
THANK YOU