Sickle cell anemia is caused by a genetic mutation that results in abnormal hemoglobin called HbS. When HbS is deoxygenated, it polymerizes inside red blood cells, causing them to take on a sickle or holly leaf shape. This leads to hemolysis, anemia, vaso-occlusive crises involving painful blockages in small blood vessels, and organ damage. The condition is most common where malaria is endemic, as the sickle cell trait provides resistance to that disease. Laboratory testing can demonstrate sickle cells on blood smears and the presence of HbS on electrophoresis.

1. Sickle cell anemia
Dr Vijay Shankar S

2. INTRODUCTION
 Haemoglobinopathy
 Qualitative abnormality
 Hb S
 Sickling of RBC’s on deoxygenation.
 Anemia, jaundice
 Autosplenectomy.

3. HEMOGLOBINOPATHIES

4. Definition
 Clinical diseases that result from a genetically
determined abnormality of the STRUCTURE
or SYNTHESIS of the hemoglobin molecule.
 The abnormality is associated with the globin
chains
 The heme portion of the molecule is normal.

5. GLOBIN ABNORMALITY
QUALITATIVE QUANTITATIVE
•Occurs as a result of
genetic mutations involving
globin protein chain
•Aminoacid deletions or
substitutions
•These mutations cause
structural variations of the
globin chains
•Hb S, Hb C, Hb M etc..
•Occurs as a result of
genetic defects that cause
reduced synthesis of globin
chains
•The globin chains are
structurally normal.
•Collectively known as
THALASSEMIAS

6. Sickle cell anemia.
 Sickle cell anemia is caused by a point mutation
at the sixth position of the β – globin chain.
 This leads to the substitution of Valine residue
for a glutamic acid residue.
 The abnormal physiochemical properties of the
resulting sickle haemoglobin(HbS) are
responsible for the sickle cell disease.

7. Sickle cell and malaria
As you can see, the areas where Malaria is present and
the Sickle Cell allele is present are overlapping.
Distribution of the sickle cell allele Distribution of Malaria

8. PATHOGENESIS
 When deoxygenated the HbS molecules undergo
aggregation and polymerization.
 Initially the red cell cytoplasm converts into
viscous fluid as the HbS aggegates.
 with continued deoxygenation, aggragated HbS
molecules assemble into long needle like
fibres within the RBC’s producing a distorted
Sickle or Holly Leaf shape.

9. Red Blood Cells from Sickle Cell Anemia
OXY-STATE DEOXY-STATE
 Deoxygenation of SS erythrocytes leads to
intracellular hemoglobin polymerization, loss of
deformability and changes in cell morphology.

10.  Sickling initially is a reversible phenomenon
 With oxygenation the HbS depolymerizes and
cell shape normalizes.
 With REPEATED EPISODES
the membrane becomes damaged and the
cells become irreversibly sickled.

11. Factors affecting the rate & degree of
sickling
1. Amount of HbS and its interactions with the
other hemoglobin chains in the cell.
Homozygous
Heterozygous
Fetal Hb inhibits polymerization
of HbS, hence newborns do not manifest until
5 – 6 months of age.

12. 2. The rate of polymerization is strongly
dependent on the hemoglobin concentration
per cell, ie MCHC.
3. Decrease in pH
4. The length of the time red cells are exposed to
low oxygen tension.
sickling of red cells is confined to microvascular beds
where the blood flow is sluggish.( Spleen and Bone
marrow)

13. PATHOPHYSIOLOGY OF SICKLE CELL ANEMIA

14. Red blood cells Going through Vessels

16. Clinical features.
 Chronic hemolysis anemia
 Ischemic tissue damage resulting from occlusion
of small blood vessels.
 Chronic hyperbilirubinemia
 Impaired growth and devolopment
 increased susceptibility to infections with
encapsulated organisms.
Pneumococci &Hemphilus
influenzae.

17. “CRISIS” in sickle cell anemia.
 VASOOCCLUSIVE CRISIS/ PAIN CRISIS:
represents episodes of hypoxic injury and
infarction associated with severe pain in the
affected region.
Most common involved sites are Bone ,
lungs , liver, brain , spleen and penis.

19.  SEQESTRATION CRISIS: occur in children
with intact spleen.
massive sequestration of the sickle red cells leads
to rapid splenic enlargement, hypovolumia nd
sopmetimes shock.

20.  APLASTIC CRISIS:
There is transient cessation of bone marrow
erythropoiesis due to an acute infection of
erythroid progenitor cells by Parvovirus B 19.
Reticulocytes disappear from the peripheral blood,
causing a sudden and rapid worsening of
anemia.

21. Lab Diagnosis
 Moderate to severe anemia.
 The blood film shows sickle cells and target cells
and show features of splenic atrophy ( howell –
jolly –bodies.)

26. Howell Jolly bodies

27. Sickling test
 The blood is deoxygenated, with the reducing
substance sodium metabisulphite placed on a
glass slide and sealed with a coverslip to prevent
reoxygenation of the cells.
 After 30 mins the blood is examined under
microscope for the presence of sickle shaped
cells.

29. Haemoglobin electrophoresis
 Absent or decreased HbA
 Demonstration of HbS
 Increase in HbF

30. Summary

31. Thank you