SICKLE CELL ANEMIA
DR.JAMILA SHEMWETA
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
