Haemoglobinopathies Flashcards
Haemoglobin structure changes depending on the globin chains involved
Which are the 3 types of Hb?
HbA (95%) 2a and 2b chains
HbA2 (<3%) 2a and 2delta
HbF (<1%) 2a and 2 gamma
How do we inherit globin genes from parents?
We have 4 alpha globin genes, 2 from each parent
We have 2 beta globin genes 1 from each parent
When beta globin genes are affected what conditions does this cause?
Sickle cell and Beta thalassaemia
When alpha globin genes are affected what conditions does this cause?
Alpha Thalassaemia
haemoglobin H disease
What is sickle cell disease?
All disease states that cause sickling of rbc
Autosomall recessive condition
What is the mutation that causes sickle cell disease?
CAG -> GTG
Causing HbS instead of HbA
What is sickle cell anaemia v sickle cell state?
Sickle cell anaemia is defined as HbSS. This is severe.
Sickle cell trait is defined as HbAS. This is usually asymptomatic, except under stress (e.g.
cold, exercise)
What are the rare forms of sickle cell?
Sickle-Haemoglobin C disease (HbSC) –
o one HbS is inherited from one parent, and one defective HbC is inherited from the other parent ⇒ HbSC.
Slightly milder than HbSS, but not always.
Sickle β thalassaemia (HbS/β) –
- One HbS from one parent and a β-thalassaemia trait/β0 from other.
- HbS-β0 similar in severity to HbSS.
When does sickle cell anaemia manifest?
at 3-6 months as foetal HbF drops
decrease in Oxygen tension causes HbS polymerisation and sickling
What can trigger Haemolytic anaemia in patients with a history of sickle cell disease?
Parvovirus B19 infection can cause aplastic crisis and haemolysis
What symptoms can occur due to aplastic crisis in sickle cell anaemia?
Haemolytic anaemia
Gallstones
Folate deficiency
Splenomegaly that becomes splenic atrophy
What are the features of vaso-occlusive crises in sickle cell disease?
Chest crises
Dacylitis
Priapism
Children: Splenic sequestration, hypersplenism, severe anaemia, shock
Stroke in children
Blood film of sickle cell disease?
Target cells
sickle cells
How to investigate and diagnose sickle cell disease?
Blood film – sickle cells and target cells.
* Sickle solubility test.
* Hb electrophoresis.
* Guthrie test at birth – to aid prompt pneumococcal prophylaxis (+ FHx).
How to treat acute sickle cell crisis?
Oxygen, fluids, opioid analgesia
Blood trasnfusion if severe e.g. chest crises
What are the concerns with top up transfusions in sickle cell patients?
Top up transfusions usually cause more harm than good, as they can increase sickling. Unless is situations were Hb is very low, i.e. <60.
++ iron overload
What prophylactic regime should sickle cell patients be on?
Penicillin V
Penumovax
HIB infection
Folic acid
What management is used for chronic sickle cell anaemia?
Hydroxycarbamide to increase HbF can help prevent crises
Regular blood transfusions
Carotid doppler monitoring
How to manage turbulent carotid blood flow in doppler in sickle cell patients?
Crizanilzumab
What is Thalassaemia?
Causes absent or defective globin chains leading to microcytic anaemia
Beta thalassaemia : reduced or absent B chains with excess α-chains
Alpha thalassaemia : reduced or absent α-chains with excess B-chains
What phenotypes of B thalassaemia exist?
β0 – no expression of the gene
β+ – some expression of the gene
β – normal gene
What can be seen on Skull X ray for B thalassaemia?
Skull bossing
Maxillary hypertrophy
hair on end sign
What is B thalassaemia minor?
E.g. having a mix of genes inherited:
- β+/ β
or
- β0 / β)
Making them asymptomatic carrier and mild hypochromic microcytic anaemia
What is B thalassaemia intermedia?
(β+/β+ or β0/β+)
So moderate anaemia
Some splenomegaly, bony deformaties, gallstones
What is B thalassaemia major?
(β0/ β0) = no B globin chains
severe microcytic anaemia, absent HbA, failure to thrive, hepatosplenomegaly (extramedullary erythropoiesis), bony deformity, severe anaemia + heart failure.
How to diagnose thalassaemia?
Should be done at Guthrie test at birth : electropheresis
How to treat Beta thalassaemia?
Blood transfusions if moderate/severe with iron chelation* to prevent overload
+ folic acid
*desferrioxamine
Which chromosome controls a-chain synthesis?
p-arms of chromosome 16
Deletion mutations of chromosome 16p cause reduced synthesis
What 4 genotypes are there of a-thalassaemia?
silent : 1 deleted gene asymptomatic
Trait : 2 deleted genes, mild microcytic anaemia
Haemoglobin H disease : 3 deleted, target cells + heinz bodies + splenomegaly
Major : 4 deleted genes, Hb barts hydrops foetalis = death in utero
How does silent alpha thalassaemia present?
Asymptomatic
How does trait alpha thalassaemia present?
Two forms exist:
if both deletions are on same chromosome (Cis deletion) = alpha-thal-1
if on different chromosomes (trans-deletion) = alpha-thal-2
= mild microcytic anaemia
How does Haemoglobin H disease alpha thalassaemia present?
microcytic anaemia
occurs with target cells and Heinz bodies.
Also associated splenomegaly.
α-thalassaemia major (–
In utero death
Haemoglobin barts hydrops foetalis
