Inherited Haemolytic Anaemia

Question 1

List some clinical features of haemolytic anaemia.

Answer 1

pallor, jaundice, splenomegaly, gallstones.

Signs of anaemia.

Question 2

List laboratory results that may indicate a haemolytic anaemia.

Answer 2

FBC: anaemia
Reticulocytes.
Blood smear: spherocytes, poikilocytes, polychromasia.
Raised bilirubin.
Raised LDH.
Low haptoglobin.

Question 3

On which chromosome is the beta gene of haemoglobin found?

Answer 3

Chromosome 11.

Question 4

On which chromosome is the alpha gene of haemoglobin found?

Answer 4

Chromosome 16.

Question 5

List some clinical features and laboratory findings for Beta Thalassemia Major.

Answer 5

Clinical features: severe anaemia, ineffective and extramedullary erythropoiesis, hepatosplenomegaly.
Laboratory features: anaemia, microcytic, hypochromic cells, target cells. BM: red cell hyperplasia. Raised iron levels. fetal haemoglobin.

Question 6

List some clinical features and laboratory findings for Beta Thalassemia Minor.

Answer 6

Single gene defect.

Hypochromic, microcytic blood film.

Question 7

Why is alpha thalassemia less common than beta?

Answer 7

Because there are two alpha genes on each of the maternal and paternal chromosomes (chr16), whereas only a single beta gene on each maternal and paternal chromosomes (Chr11).

Question 8

Briefly describe the pathophysiology behind sickle cell anaemia.

Answer 8

Substitution of valine for glutamic acid in the 6th position of the beta chain, due to a single base change of GAG to GTG.
HbS is insoluble at low oxygen tensions and leads to crystallisation, RBCs become sickled in appearance.

Question 9

Briefly describe the pathophysiology behind hereditary spherocytosis.

Answer 9

Mutations in ankyrin or spectrin, RBC membrane proteins, resulting in loss of membrane surface area and leading to splenic entrapment and destruction by macrophages.