Macrocytic anaemia with megaloblastic signs Flashcards
What is macrocytic anaemia?
Macrocytic anaemia is a blood disorder that causes your bone marrow to make abnormally large red blood cells.
Megaloblastic anaemia is an example of macrocytic anaemia.
How does megaloblastic anaemia occur?
Occurs due to defective DNA synthesis (megaloblasts), this is characterised by the presence of erythroblasts with delayed nuclear maturation in the bone marrow
What are the causes of vitamin B12 deficiency that can lead to megaloblastic anaemia?
Low dietary intake e.g. veganism
Pernicious anaemia
Other causes include gastrectomy and congenital deficiency of intrinsic factor
What is pernicious anaemia?
An autoimmune condition with resulting destruction of gastric parietal cells results in intrinsic factor deficiency with B12 malabsorption and deficiency.
Often associated with atrophic gastritis and personal or family history of other autoimmune disorders.
What are the causes of folate deficiency that can lead to megaloblastic anaemia?
Inadequate intake (found in leafy green vegetables)
Malabsorption
Excess utilisation - haemolysis, exfoliating dermatitis, pregnancy and malignancy.
Drugs - anticonvulsants
Apart from folate deficiency and vitamin B12 deficiency, what are other causes of megaloblastic anaemia?
Drugs
Rare inherited abnormalities
What is a megaloblast?
An abnormally large nucleated red cell precursor with an immature nucleus
What are megaloblastic anaemias characterised by?
Megaloblastic anaemias are characterised by a lack of red cells due to predominant defects in DNA synthesis in developing precursor cells (megaloblasts) in the marrow
What is the food source for vitamin B12?
Animal
How long does the body store vitamin B12 for?
2-4 years
Where in the body is vitamin B12 absorbed?
Ileum
What is the daily requirement for vitamin B12?
1.5 micrograms/day
What is the food source for folate?
Liver, leafy vegetables and fortified cereals
How long does the body store folate for?
4 months
Where in the body is folate absorbed?
Duodenum and jejunum
What is the daily requirement for folate?
200 micrograms/day
Clinical features of B12/folate deficiency?
Signs + symptoms of anaemia
Weight loss, diarrhoea, infertility
Sore tongue, jaundice
Development problems
Patients with macrocytic anaemia may appear jaundiced
- This is due to ineffective erythropoiesis caused by intramedullary haemolysis, meaning a breakdown of cells within bone marrow.
B12 deficiency can also present with neurological problems - posterior/dorsal column abnormalities, neuropathy, dementia and psychiatric manifestations.
Investigations for macrocytic anaemia?
FBC: macrocytic anaemia, pancytopenia in some patients.
Blood film: macrovalocytes and “hypersegmented” neutrophils (normally 3-5 nuclear segments)
Assay B12 and folate levels in serum: low levels may not always indicate deficiency and normal levels may not always indicate normalcy.
Check for auto-antibodies:
- Anti gastric-parietal cell (sensitive not specific)
- Anti intrinsic factor (specific not sensitive)
Management of macrocytic anaemia?
Treat the cause where possible
Vitamin B12 injections for life in pernicious anaemia
Folic acid tablets 5mg/day PO
Red cell transfusion - only in potentially life-threatening anaemia
What is the mean corpuscular volume (MCV)?
The mean corpuscular volume (MCV) is the measure of the average red blood cell size.
What is the difference between microcytic and macrocytic anaemia?
Macrocytic anaemia occurs when the MCV is greater than 100 fL, and the red cells are larger and fewer than normal.
Microcytic anaemia occurs when the MCV is less than 80 fL, and the red cells are smaller and often have low haemoglobin content
Difference between sensitivity and specificity?
Sensitivity (true positive rate) is the probability of a positive test result, conditioned on the individual truly being positive.
Specificity (true negative rate) is the probability of a negative test result, conditioned on the individual truly being negative.
So test that is high sensitivity means that A POSITIVE IS A POSITIVE so there is low chance of a false negative, vice versa for a highly specific test.
