Haem: Thalassaemia & G6PD Flashcards
What is thalassaemia?
Refers to a genetic defect in the protein chains that make up Hb.
Defects in the alpha globin chains –> alpha thalassaemia.
Defects in beta globin chains –> beta thalassaemia
Inheritance of thalassaemia?
Autosomal recessive
What is the overall effect of thalassaemia?
Varying degrees of anaemia, depending on the type and mutation.
What causes splenomegaly in thalassaemia?
In patients with thalassaemia, the RBCs are more fragile and breakdown more easily.
In patients with thalassaemia, the spleen collects all the destroyed RBCs, resulting in splenomegaly (as the spleen normally acts as a sieve to filter the blood and remove older blood cells).
How is the bone marrow affected in thalassaemia?
The bone marrow expands to produce extra RBCs to compensate for the chronic anaemia.
This causes a susceptibility to fractures and prominent features, such as a pronounced forehead and malar eminences (cheek bones).
Signs & symptoms of thalassaemia?
- Microcytic anaemia
- Fatigue
- Pallor
- Jaundice
- Gallstones
- Splenomegaly
- Poor growth and development
- Pronounced forehead and malar eminences
Investigations in thalassaemia?
1) FBC: microcytic anaemia
2) Haemoglobin electrophoresis: used to diagnose globin abnormalities
3) DNA testing: can be used to look for the genetic abnormality
Screening for thalassaemia?
Pregnant woman offered screening test at booking visit.
Management of thalassaemia?
Repeated transfusion
What is a key complication of repeated transfusion in thalassaemia?
Iron overload –> organ failure.
Iron chelation therapy is therefore important (e.g. desferrioxamine)
Iron overload in thalassaemia causes effects similar to haemochromatosis.
What are some symptoms?
- Fatigue
- Liver cirrhosis
- Infertility
- Impotence
- Heart failure
- Arthritis
- Diabetes
- Osteoporosis and joint pain
Beta thalassaemia minor vs intermedia vs major?
Minor –> carriers of an abnormally functioning beta globin gene i.e. they have one abnormal and one normal gene.
Intermedia –> have two abnormal copies of the beta globin gene (can be either two defective genes or one defective gene and one deletion gene).
Major –> homozygous for the deletion genes i.e. have no functioning beta globin genes at all.
Give 3 complications of thalassaemia major?
1) Severe microcytic anaemia
2) Splenomegaly
3) Bone deformities
What can potentially be curative in thalassaemia?
Bone marrow transplant
What is hereditary spherocytosis?
A condition where the RBCs are sphere shaped, making them fragile and easily destroyed when passing through the spleen.
What is the most common inherited haemolytic anaemia in NORTHERN Europeans?
Hereditary spherocytosis
Inheritance of hereditary spherocytosis?
Autosomal dominant
Presentation of hereditary spherocytosis?
- Jaundice
- Anaemia
- Gallstones
- Splenomegaly
Patients can have episodes of haemolytic crisis.
What is this?
These are often triggered by infections, where the haemolysis, anaemia and jaundice is more significant.
Patients with hereditary spherocytosis can develop aplastic crisis.
What happens during aplastic crisis?
There is ncreased anaemia, haemolysis and jaundice, without the normal response from the bone marrow of creating new RBC.
Usually the bone marrow will respond to haemolysis by producing red blood cells faster, demonstrated by extra reticulocytes (immature red blood cells) in the blood. In aplastic crisis there is no reticulocyte response.
What is aplastic crisis in hereditary spherocytosis typically preceeded by?
Infection with parvovirus
What is seen on a blood film in hereditary spherocytosis?
Spherocytes
How is the mean corpuscular haemoglobin concentration (MCHC) affected in hereditary spherocytosis?
Raised MCHC
Reticulocytes in hereditary spherocytosis?
Raised
Management of hereditary spherocytosis?
Treatment is with folate supplementation and splenectomy.
Removal of the gallbladder (cholecystectomy) may be required if gallstones are a problem.
Transfusions may be required during acute crises.
What is G6PD deficiency?
There is a defect in the G6PD enzyme normally found in all cells in the body.
This causes crises that are triggered by infections, medications or fava beans (broad beans).
Inheritance of G6PD deficiency?
X-linked recessive (i.e. usually affects males).
What is the G6PD enzyme responsible for?
Helping protect cells from damage by reactive oxygen species (ROS).
This enzyme is particularly important in RBCs.
What are ROS?
ROS are reactive molecules that contain oxygen, produced during normal cell metabolism and in higher quantities during stress on the cell.
What is the effect of a G6PD deficiency?
A deficiency in G6PD makes cells more vulnerable to ROS, leading to haemolysis in red blood cells.
Periods of increased stress, with a higher production of ROS, can lead to acute haemolytic anaemia.
How does G6PD often initially present?
Neonatal jaundice.
Features of G6PD deficiency?
1) neonatal jaundice
2) anaemia
3) Intermittent jaundice, particularly in response to triggers
4) Gallstones
5) Splenomegaly
What may be seen on a blood film in G6PD deficiency?
Heinz bodies
What are Heinz bodies?
Heinz bodies are blobs of denatured haemoglobin (“inclusions”) seen within the red blood cells.
How is a diagnosis of G6PD deficiency made?
G6PD enzyme assay.
What is a key exam trigger for G6PD crisis?
Fava (broad) beans
What are some medications that trigger haemolysis and should be avoided in G6PD deficiency?
Primaquine (an antimalarial)
Ciprofloxacin
Nitrofurantoin
Trimethoprim
Sulfonylureas (e.g gliclazide)
Sulfasalazine and other sulphonamide drugs
