Haemoglobinopathies

Question 1

What is the structure of Hb?

Answer 1

Tetramer made up of 2 alpha globin and 2 beta globin chains

1 haem group attached to each globin chain

Question 2

What are the 3 major forms of Hb?

Answer 2

HbA (2 alpha 2 beta)
HbA2 (2 alpha 2 delta)
HbF (2 alpha 2 gamma)

Question 3

Which chromosomes are alpha like geneson?

Answer 3

Chromosome 16

Question 4

What chromosome are beta like genes on?

Answer 4

Chromosome 11

Question 5

At what age are adult levels of Hb reached?

Answer 5

6-12 months

Question 6

What are haemoglobinopathies?

Answer 6

Hereditary conditions affecting globin chain synthesis?

Question 7

What is the difference between the 2 main groups of haemoglobinopathies?

Answer 7

Thalassaemias (decreased rate of globin chain synthesis)

Structural Hb variants (normal production of structurally abnormal globin chains)

Question 8

What are the 2 types of thalassaemias?

Answer 8

Alpha & Beta

Question 9

How do thalassaemias affect normal physiology?

Answer 9

Inaequate Hb production (microcytic hypochromic anaemia)

Unbalanced accumulation of globin chains (ineffective erythropoiesis & haemolysis)

Question 10

How are alpha thalassaemias classified?

Answer 10

a thal trait (1 or 2 genes missing)
HbH disease (only 1 alpha gene left)
Hb Barts hydrops fetalis (no functional alpha genes)

Question 11

How can alpha thal trait be distinguished from iron deficiency?

Answer 11

alpha thal - normal ferritin & red blood cell count raised

Question 12

How would HbH disease present on FBC?

Answer 12

Anaemia with very low MCV and MCH

Question 13

How does HbH disease look on a blood film?

Answer 13

Excess B chains form tetramers called HbH wich cannot carry oxygen
HbH bodies can be seen with special stains

Question 14

Clinical features of HbH disease

Answer 14

Splenomegaly
Jaundice 9aemolysis & ineffectiveerythropoiesis)
Can present from mild anaemia to transfusion dependent

Question 15

Clinical features of Hb Bart’s Hydrops fetalis syndrome

Answer 15

Severe anaemia 
Cardiac failure, oedema 
Growth retardation
Severe hepatosplenomegaly 
Skeletal and CV abnormalities 
Most dieinutero

Question 16

Clinical features of B thalassaemia

Answer 16

Presents aged 6-24 months
Failure to thrive
Pallor
Extramedullary haematopoiesis (hepatosplenomegaly, skeletal changes, organ damage

Question 17

Management of B thal major

Answer 17

Lifelong transfusion programme

Question 18

What is the main cause of mortality for patients being treated for B thal major?

Answer 18

Iron overload

Question 19

What are the endocrine consequences of iron overload?

Answer 19

Impaired growth and pubertal development
Diabetes
Osteoporosis

Question 20

What are the cardiac complications of iron overload?

Answer 20

Cardiomyopathy Arrhythmias

Question 21

How is iron overload treated?

Answer 21

Iron chelating drugs (Desferrioxamine) -binds toron and are excreted in urine or stool

Question 22

Why are patients being treated for B thal major at higher risk of bacterial sepsis?

Answer 22

Because they can have iron overload and bacteria like iron

Question 23

How can thalassaemias be diagnosed?

Answer 23

Blood film (hypochromia, target cells, anisopoikilocytosis0
HPLC  (quantifies different types of Hb)

Question 24

What is the pathophysiology of sickling disease?

Answer 24

Point mutation in codon 6 ofthe B globin gene - alters structure of resulting Hb (HbS)
HbS polymerises if exposed to low oxygen levels for a prolonged period
Distorts the red cell damaging the RBC membrane

Question 25

How is sickle cell anaemia transmitted?

Answer 25

Autosomal recessive

Question 26

What is sickle crisis?

Answer 26

Episodes of tissue infarction due to vascular occlusion

Question 27

Symptoms of sickle cell anaemia?

Answer 27

Dactylitis, bone marrow, lung, spleen, CNS - pain may be extremely severe

Question 28

What are the life threatening complications of sickle cell anaemia?

Answer 28

Sequestration of sickled RBCs in liver and spleen

Hyposplenism (due to repeated infarcts0

Question 29

What can precipitate sickle crisis?

Answer 29

Hypoxia 
Dehydration 
Infection
Cold exposure 
Stress/fatigue

Question 30

How do you treat painful sickle crisis?

Answer 30

Opiate analgesia 
Hydration
Rest 
Oxygen 
Red cell exchange in severecrises

Question 31

What is the long term treatment of sickle cell anaemia?

Answer 31

Reduce risk of infection
Folid acid (increase RBC turnover
Hydroxycarbamide can reduce severity of disease by inducing HbF production

Question 32

Which milder form of sickling disorder has increased risk of thrombosis?

Answer 32

HbSC disease