Congenital Anaemias

Question 1

What areas can be affected leading to a congenital anaemia?

Answer 1

• The red cell Membrane
• Metabolic pathways
• Synthesis of Haemoglobin

Question 2

The main cause of Red Cell Membrane problem is…

Answer 2

Hereditary Spherocytosis (HS)

Question 3

What is Hereditary Spherocytosis?

Answer 3

An autosomal Dominant defect in 5 structural proteins that leads to spherical red cells
They get removed from circ by the RE system

Question 4

How would someone with HS present?

Answer 4

• Haemolytic Anaemia
• Neonatal Jaundice
• Splenomegaly
• pigment gallstones

Question 5

How would we treat HS?

Answer 5

Folic Acid
Transfusion
Splenectomy

Question 6

What’s the main problem with metabolic pathways that can lead to anaemia?

Answer 6

Glucose 6 Phosphate Dehydrogenase (G6PD) Deficiency

X linked, affecting males and carrying in females

Question 7

How does G6PD deficiency present?

Answer 7

Neonatal Jaundice
Splenomegaly
Pigment Gallstones
Anaemia

Drug, broad bean, infection can precipitate –> jaundice, anaemia & haemoglobinuria, intravascular hemolysis

Question 8

What can cause an episode of haemolysis in G6PD deficiency?

Answer 8

• Broad aka fava beans
• Infection
• Drugs:
  Antimalarials, sulphonamides, nitrofurantoin, aspirin, antihelminthics & Vit K analogues

Question 9

There are 2 categories of condition affecting your Globin chains:

Answer 9

1- Reduced/ absent globing chain production: Thalassaemias

2- Mutations to structurally abnormal global chain: Sickle Cell

Question 10

What are the major types of Thalassaemias?

Answer 10

Homozygous Alpha Zero Thalassaemia = No alpha chains

Beta Thalassaemia Major = No Beta chains

Non-transfusion dependant Thalassaemias

Thalassaemia Minor = Carrier State

Question 11

How does Homozygous Alpha Zero Thalassaemia present?

Answer 11

They get hydrops Fetalis so stillborn- incompatible with life

you can get alpha thalassaemias that cause less disruption and so are survivable

Question 12

A sickly 4 month old comes in, on investigation they are severely anaemic and show bony deformities, splenomegaly and growth retardation. what thalassaemia could it be?

Answer 12

Beta Thalassaemia Major

Tends to present at 3-6 months with severe anaemia, deformity, splenomegaly and growth problems, expansion of ineffective bone marrow

Question 13

How can we treat Beta Thalassaemia Major?

Answer 13

4-6 wkly transfusions (hence Transfusion Dependant Anaemia)
Plus Iron Chelation therapy to prevent Iron overload from the transfusions (this can kill you from heart/liver failure)

Bone Marrow Transplant

Question 14

How is Sickle Cell Disease inherited?

Answer 14

Autosomal Recessive

Question 15

How does Sickle Cell cause problems?

Answer 15

You do get a haemolytic anaemia but the worst problems come with vaso-occlusion due to the weird shaped cells

Question 16

What are the major problems that sickle cell causes?

Answer 16

• Stroke
• Hyposplenism –> high infection risk
• Chronic Haemolytic anaemia (+gallstones & aplastic crisis)
• Sequestration Crises (spleen/liver)
• Chest Crisis
• Painful Vaso-occlusive crisis

Can also cause lots of other infarcts e.g. pulm, renal, retinopathy & bone necrosis
As well as Cardiomegaly –> HF

Question 17

How do you treat a Sickle cell patient with a Painful Vaso-occlusive crisis?

Answer 17

Pain relief incl Opiates
Fluids
O2
Abx if infected

Question 18

How would a Chest crisis present in sickle cell?

Answer 18

Chest pain, fever & worsening hypoxia

Plus infiltrates visible on x-ray

Question 19

How do we treat a chest-crisis in sickle cell?

Answer 19

Resp support
Abx
Fluids
Analgesia
Transfusion

Question 20

What can we give sickle cell patients as prophylaxis?

Answer 20

Vaccinate (prone to inf)
Penicillin &Anti-malarials (again inf)
Folic Acid (reduce anaemia)

Question 21

What treatments can we give for the actual Sickle Cell Disease (not the acute events)?

Answer 21

Transfusion
Disease Modifying Drugs - Hydroxycarbamide (actually a cause of Macrocytic anaemia)
Bone Marrow Transplant
Gene Therapy

Question 22

What’s cool about a G6PD deficiency?

If you don’t think this is cool you don’t deserve to get this right

Answer 22

It protects you against malaria so it’s much more common in those parts of the world

Being a carrier of sickle cell also makes you resistant to malaria, however having Sickle Cell Disease makes you more prone to it so you have to take prophylactic drugs

Question 23

What do defects in haem synthesis cause?

Answer 23

In mitochondrial part –> Sideroblastic anaemia

In the cytoplasmic part –> Porphyrias

Question 24

What is another rare enzyme deficiency leading to congenital anaemia?

Answer 24

Pyruvate kinase deficiency

• Reduced ATP
• Increased 2,3-DPG
• Cells rigid