Sickle cell anaemia

Dr Nikhil BansalJ.N.M.C.,Wardha

Introduction :-

It is a haematological disorder which results due to the inheritance of an autosomal recessive trait.

It results due to a single glutamic acid to valine substitution at the position 6 of the beta globin polypeptide chain.

Homozygotes (termed SS) produce only abnormal beta chains that make only haemoglobin S (HbS).

This gives rise to sickle cell anaemia.

Heterozygotes (termed AS) produce a mixture of normal and abnormal beta chains making HbA and HbS both.

This gives rise to the clinically asymptomatic sickle trait.

Inheritance pattern :-

AS AS

AS AS SSAA(Normal)

(Sickle cell trait)

(Sickle cell disease)

Possible genotype of the offspring of parents with the sickle cell trait

Epidemoilogy:-

This disease is profound in the mainly central Africa, Madagascar, south-eastern coastal areas of India , the European nations along the Mediterranean coast like Italy, Spain, Portugal ,Arab nations like Oman, Saudi Arabia .

Pathogenesis :- The main role in pathogenesis is played

by the HbS.

Deoxygenation of HbS leads to formation of pseudocrystalline structures called ”TACTOIDS”

These tactoids distort the red cell membrane,thus forming sickle shaped cells.

Now ,if reoxygenation occurs, this polymerisation is reversible.

BUT,the distortion which has already occurred may become irreversible.

This leads to the formation of “IRREVERSIBLY SICKLED” red cells.

More the amount of HbS, more easily occurs the formation of TACTOIDS.

Influence of other abnormal haemoglobins on sickle cell polymerisation:-

HbC participates more readily

HbA participates but less readily

HbF strongly inhibits the process

Clinical features :-

Hypoxia Acidosis Dehydration Infection Plugging of blood vessels leading to

“CRISES”

The “CRISES”

1)Vaso – occlusive crisis :-

Plugging of small vessels in the bone

Severe bone pain

Damage to areas producing bone marrow

Tachycardia ,sweating and fever

The most common crisis

2)Sickle chest syndrome :-Follows on from a vaso–occlusive crisis

Bone marrow infarction

Fat emboli in lungs

Further infarction

Ventilatory failure

DEATH

3)Sequestration crisis :-

Thrombosis of veinous outflow

Massive splenic enlargement

Hepatic sequestration with pain

Circulatory collapse

DEATH

4)Aplastic crisis :-

Adult sickle cell anaemia case

Infection with parvovirus B19

Red cell aplasia (self limiting but severe)

Very low Hb count

Heart failure

Investigations :- Hb count as low as 6-8 g/dl

Blood film

Reticulocyte count

Detection of the presence of HbS by exposing the RBC’s to sodium dithionite.

Hb electrophoresis (definitive diagnosis)

Management :-

Prophylaxis with daily folic acid, penicillin V for protection against pneumococcal infection.

Vaccination against pneumococcus, haemophilus & hepatitis B.

Vaso-occlusive crisis – aggressive rehydration, oxygen therapy, analgesics & antibiotics.

Sequestration & aplastic crises – transfusion of fully genotyped blood.

Exchange transfusion of HbS with HbA. Administration of agents which induce

increased synthesis of HbF viz hydroxycarbamide thus inhibiting polymerisation of HbS.