Congenital Anaemias Flashcards
What areas can be affected leading to a congenital anaemia?
- The red cell Membrane
- Metabolic pathways
- Synthesis of Haemoglobin
The main cause of Red Cell Membrane problem is…
Hereditary Spherocytosis (HS)
What is Hereditary Spherocytosis?
An autosomal Dominant defect in 5 structural proteins that leads to spherical red cells
They get removed from circ by the RE system
How would someone with HS present?
- Haemolytic Anaemia
- Neonatal Jaundice
- Splenomegaly
- pigment gallstones
How would we treat HS?
Folic Acid
Transfusion
Splenectomy
What’s the main problem with metabolic pathways that can lead to anaemia?
Glucose 6 Phosphate Dehydrogenase (G6PD) Deficiency
X linked, affecting males and carrying in females
How does G6PD deficiency present?
Neonatal Jaundice
Splenomegaly
Pigment Gallstones
Anaemia
Drug, broad bean, infection can precipitate –> jaundice, anaemia & haemoglobinuria, intravascular hemolysis
What can cause an episode of haemolysis in G6PD deficiency?
- Broad aka fava beans
- Infection
- Drugs:
Antimalarials, sulphonamides, nitrofurantoin, aspirin, antihelminthics & Vit K analogues
There are 2 categories of condition affecting your Globin chains:
1- Reduced/ absent globing chain production: Thalassaemias
2- Mutations to structurally abnormal global chain: Sickle Cell
What are the major types of Thalassaemias?
Homozygous Alpha Zero Thalassaemia = No alpha chains
Beta Thalassaemia Major = No Beta chains
Non-transfusion dependant Thalassaemias
Thalassaemia Minor = Carrier State
How does Homozygous Alpha Zero Thalassaemia present?
They get hydrops Fetalis so stillborn- incompatible with life
you can get alpha thalassaemias that cause less disruption and so are survivable
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?
Beta Thalassaemia Major
Tends to present at 3-6 months with severe anaemia, deformity, splenomegaly and growth problems, expansion of ineffective bone marrow
How can we treat Beta Thalassaemia Major?
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
How is Sickle Cell Disease inherited?
Autosomal Recessive
How does Sickle Cell cause problems?
You do get a haemolytic anaemia but the worst problems come with vaso-occlusion due to the weird shaped cells
What are the major problems that sickle cell causes?
- 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
How do you treat a Sickle cell patient with a Painful Vaso-occlusive crisis?
Pain relief incl Opiates
Fluids
O2
Abx if infected
How would a Chest crisis present in sickle cell?
Chest pain, fever & worsening hypoxia
Plus infiltrates visible on x-ray
How do we treat a chest-crisis in sickle cell?
Resp support Abx Fluids Analgesia Transfusion
What can we give sickle cell patients as prophylaxis?
Vaccinate (prone to inf)
Penicillin &Anti-malarials (again inf)
Folic Acid (reduce anaemia)
What treatments can we give for the actual Sickle Cell Disease (not the acute events)?
Transfusion
Disease Modifying Drugs - Hydroxycarbamide (actually a cause of Macrocytic anaemia)
Bone Marrow Transplant
Gene Therapy
What’s cool about a G6PD deficiency?
If you don’t think this is cool you don’t deserve to get this right
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
What do defects in haem synthesis cause?
In mitochondrial part –> Sideroblastic anaemia
In the cytoplasmic part –> Porphyrias
What is another rare enzyme deficiency leading to congenital anaemia?
Pyruvate kinase deficiency
- Reduced ATP
- Increased 2,3-DPG
- Cells rigid
