Haemoglobinopathies sickle cell anemia

Sickle cell anemia

Dr Vijay Shankar S

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

HEMOGLOBINOPATHIES

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.

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

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.

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

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.

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.

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.

Factors affecting the rate & degree of sickling

1. Amount of HbS and its interactions with the other hemoglobin chains in the cell.

HomozygousHeterozygousFetal Hb inhibits

polymerization of HbS, hence newborns do not manifest until 5 – 6 months of age.

2. The rate of polymerization is strongly dependent on the hemoglobin concentration per cell, ie MCHC.

3. Decrease in pH4. 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)

PATHOPHYSIOLOGY OF SICKLE CELL ANEMIA

Red blood cells Going through Vessels

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.

“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.

SEQESTRATION CRISIS: occur in children with intact spleen.

massive sequestration of the sickle red cells leads to rapid splenic enlargement, hypovolumia nd sopmetimes shock.

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.

Lab Diagnosis Moderate to severe anemia. The blood film shows sickle cells and

target cells and show features of splenic atrophy ( howell – jolly –bodies.)

Howell Jolly bodies

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.

Haemoglobin electrophoresis

Absent or decreased HbA Demonstration of HbS Increase in HbF

Summary

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