Haemoglobinopathies and haemolytic anaemias Flashcards
What are Haemoglobinopathies?
Inherited disorders that are typically autosomal recessive (abnormal globin chain expression)
-reduced/absent expression of globin chains or an altered structure leading to instability and/or dysfunctional
What are Thalassaemias?
Heterogenous group of genetic disorders which leads to a defect in regulation of expression of globin genes
Where is Beta Thalassaemia more prevalent?
South Asia
Mediterranean
Middle East
Where is Alpha Thalassaemia more prevalent?
Far east
Describe Alpha Thalassaemia
Deletion of 1 or more alpha globin chain
humans usually have 4 alpha globin - 2 maternal and 2 paternal on Chr 16
Describe the types of Alpha Thalassaemia
4 types based on the number of alpha globin genes deleted:
1) Silent carrier disease = asymptomatic
2) Alpha Thalassaemia trait = minimal or no anaemia; microcytosis and hypochromic
3) Haemoglobin H disease = moderately severe; microcytic, hypochromis and heinz bodies
4) Hydrops fetalis = incompatible with life
Describe the (3) types of Beta Thalassaemia
1) B thalassaemia minor/ trait = usually asymptomatic with a mild anaemia; heterozygous with 1 normal and 1 abnormal gene
2) B thalassaemia intermedia = severe anaemia (not enough to require regular blood transfusions); genetically heterogenous
3) B thalassaemia major = severe transfusion dependent; homozygous
Describe characteristics of a thalassaemia blood smear
- Hypochromic
- Microcytic
- Anisopoikilocytosis
- Heinz bodies can be seen
What are the consequences of thalassaemia?
- Extramedullary haematopoiesis (to compenste)
- Splenomegaly and/or hepatomegaly
- Reduced O2 delivery leads to stimulation of EPO
- Iron overload (from ineffective haemopoiesis)
Treatments for thalassaemia
- Red cell transfusion
- Iron chelation (to delay overload of iron)
- Folic acid (support erythropoiesis)
- Immunisation (they’re prone to infection)
What is sickle cell disease?
- an autosomal recessive disease from mutation of beta globin gene
- GLU substituted to VAL in the 6th position
- red blood cells become a sickle shaped
Describe how sickle cells cause anaemia
- In the low oxygen state, deoxygenated HbS forms polymers that cause a sickle shape
- irreversibly sickled red cells are less deformable and can cause occlusion in small blood vessels (sticky)
What are the 3 clinical patterns of sickle cell anaemia?
1) Vaso-occlusive = painful bone crises
2) Aplastic (often triggered by parvovirus)
3) Haemolytic
What are the consequences of sickle cell anaemia?
- retinopathy
- splenic atrophy
- avascular necrosis (e.g. in femoral head)
- acute chest syndrome
- stroke
- osteomyelitis
- skin ulcers
Describe haemolytic anaemia
- haemolysis reduces lifespan of RBCs
- can be intavascular (in blood vessels) or extravascular (in the spleen)
- BM compensates by increased production but only to a certain point (anaemia arises when haemolysis>BM capacity)
