Haemoglobinopathies (CH)

Question 1

What are haemoglobinopathies?

Answer 1

Group of recessively inherited conditions affecting the haemoglobin component of blood

Question 2

What are some types of haemoglobin? (3)

Answer 2

• HbF: 2 alpha globin + 2 gamma globin
• HbA: 2 alpha globin + 2 beta globin
• HbA2: 2 alpha globin + 2 delta globin

Question 3

What are the two types of haemoglobinopathies?

Answer 3

• change in structure and quality of Hb - haemoglobin variants e.g. HbS (sickle cell)
• reduction in quantity of Hb - alpha/beta thalassaemia (reduced globin synthesis)

Question 4

What are the two types of thalassaemia?

Answer 4

• beta-thalassaemia (most common in those of Mediterranean descent)
• alpha-thalassaemia (most common in those of Asian and African descent)

Question 5

What are the two main forms of beta-thalassaemia? (2+1)

Answer 5

• beta thalassaemia minor AKA trait (one defective allele/beta-globin gene)
• beta thalassaemia major (two defective alleles/beta-globin genes)
  
  • beta thalassaemia intermedia = intermediate severity; non-transfusion dependent (does not need regular transfusion therapy to maintain Hb level and QoL)

Question 6

What are the four types of alpha-thalassaemia?

Answer 6

• silent carrier (1 affected allele/alpha-globin gene)
• alpha thalassaemia trait (two defective alleles/alpha-globin genes)
• haemoglobin H disease (three defective alleles/alpha-globin genes) - deletional vs non-deletional forms
• alpha thalassaemia major AKA Hb Bart hydrops fetalis syndrome (four defective alleles - deletion of all 4 alpha-globin genes)

Question 7

List clinical features of beta-thalassaemia minor. (2)

Answer 7

• asymptomatic
• mild microcytic hypochromic anaemia (microcytosis is usually disproportionate to anaemia)

Question 8

List clinical features of beta-thalassaemia major. (5)

Answer 8

• severe haemolytic anaemia (lethargy, pallor)
• hepatosplenomegaly (–> abdominal distension)
• skeletal deformities (spinal changes, osteopenia)
• failure to gain weight + low weight and height
• large head

Question 9

List clinical features of a silent carrier (alpha-thalassaemia). (2)

Answer 9

• asymptomatic
• no anaemia

Question 10

List clinical features of alpha-thalassaemia trait. (2)

Answer 10

• microcytic hypochromic red cells
• no anaemia

Question 11

List clinical features of haemoglobin H disease (alpha-thalassaemia). (3)

Answer 11

• microcytic hypochromic anaemia
• splenomegaly
• growth retardation

Question 12

List clinical features of alpha-thalassaemia major AKA haemoglobin Bart disease.

Answer 12

Intrauterine death

Question 13

What are the first-line investigations in thalassaemia?

Answer 13

• bloods - FBC, RBC, Hb, MCV, MCH, reticulocytes
• peripheral smear
• Hb electrophoresis

Question 14

What would Hb-electrophoresis show in beta-thalassaemia? (3)

Answer 14

• HbA2 levels raised in beta-thalassaemia trait and major (2a and 2 delta chains)
• absent HbA
• also raised HbF - because HbA (2a and 2b chains) cannot be produced

Question 15

What will Hb-electrophoresis show in alpha-thalassaemia?

Answer 15

HbH band (and Hb Bart, and concomitant haemoglobinopathies e.g. HbE, HbS, HbC, HbD)

Will not pick up alpha-thalassaemia silent carrier or trait outside of the newborn period, and will not differentiate deletional from non-deletional HbH

Question 16

What will bloods show in thalassaemia? (2)

Answer 16

• microcytic hypochromic anaemia
• raised reticulocytes

Question 17

What is the management plan for thalassaemia MAJOR (alpha/beta)?

Answer 17

• lifelong blood transfusion
• this can cause iron overload –> organ failure
• iron chelation therapy (desferrioxamine) prescribed alongside transfusion therapy to prevent this

Question 18

What can we offer to relatives of patients with thalassaemia? (2)

Answer 18

• genetic counselling
• screening tests