Session 5 - Haemolytic Anaemia and Haemoglobinopathies Flashcards
What is sickle cell anaemia?
A genetic disorder that leads to abnormally shaped red blood cells.
Their abnormal shape leads to the occlusion of small blood vessels.
Describe the genetic mutation that leads to sickle cell anaemia. Also describe how this causes the sickle shape.
An autosomal recessive mutation to the B-globin gene:
In a single nucleotide polymorphism a glutamic acid is changed for a valine.
The mutated haemoglobin protein is known as HbS.
HbS acts normally under normal oxygen saturations.
Under low oxygen saturations HbS forms polymers inside the cell that lead to the sickle shape.
If this happens repeatedly the cell may become irreversibly sickled.
Name three clinical consequences of sickle cell anaemia:
Stroke
Kidney infarcts
Splenic atrophy
What is thalassaemia?
The quarternary structure of haemoglobin is affected by a deviation to the 1:1 ratio of a-globin to b-globin chains.
You can have either a B thalassaemia or a A thalassaemia.
The severity increases depending on how many genes are affected.
Haemoglobin with an excess of one globin chain or another will form unstable tetramers which have abnormal oxygen dissociation curves.
What are the consequences of thalassaemia?
There are less functional erythrocytes produced in bone marrow. Therefore extramedullary haemopoiesis occurs to compensate. I.e haemopoiesis in the liver and spleen. Haemopoiesis also expands into the cortical bone.
This results in splenomegaly, hepatomegaly and skeletal abnormalitites.
Reduced oxygen delivery leads to increased production of erythropoietin leading to further production of defective eryhthrocytes.
Iron overload also occurs because iron is not effectively used for haemopoiesis and because of the repetitive blood transfusions used to treat the anaemia.
What will a blood film from a patient with thalassaemia show?
Hypochromic cells. Microcytic cells. Target cells. Nucleated red blood cells. Heinz bodies.
How is thalassaemia treated?
Blood transfusion (to supply functional erythrocytes). Iron chelation (delays iron overload). Folic acid to support erythropoiesis.
What are haemolytic anaemias?
An anaemia that occurs because the rate at which RBCs are being destroyed exceeds the rate of erythropoiesis in bone marrow.
How can haemolytic anaemia be classified and give examples of each:
Inherited:
Glycolysis defects - RBC dies because it can’t produce enough energy.
Pentose-P pathway - RBC is destroyed due to oxidative damage.
Membrane Protein defects e.g Hereditary Spherocytosis.
Haemoglobin defects e.g Sickle cell.
Acquired:
Mechanical damage - Shear stress as cells pass through defective heart valve.
Heat damage - From severe burns.
Enzymatic damage.
Antibody damage - Autoantibodies bind to RBC causing it to be removed by the spleen.+
Oxidant damage.
What are some key labaratory findings for haemolytic anaemia?
Reticulocyte count - High in an effort to produce more erythrocytes.
Bilirubin levels - High because of the excessive haemoglobin breakdown in the liver.
Lactate Dehydrogenase - RBCs are rich in this enzyme.
What are myeloproliferative neoplasms? List the four major types:
Diseases of the bone marrow in which a specific cell is overproduced.
- Polycythaemia Vera
- Essential thrombocythaemia
- Primary myelofibrosis
- Chronic Myeloid Leukaemia
What is polycythaemia and polycythaemia vera?
Polycythaemia is a condition characterised by an excessive volume percent of erythrocytes in the blood (haematocrit).
Relative polycythaemia is due to a decrease in the plasma volume.
Absolute polycythaemia is due to an increase in the number of erythrocytes in the blood.
Polycythaemia Vera is a genetic disease which results in the bone marrow overproducing erythrocytes.
