Macrocytic anaemia with megaloblastic signs

Question 1

What is macrocytic anaemia?

Answer 1

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.

Question 2

How does megaloblastic anaemia occur?

Answer 2

Occurs due to defective DNA synthesis (megaloblasts), this is characterised by the presence of erythroblasts with delayed nuclear maturation in the bone marrow

Question 3

What are the causes of vitamin B12 deficiency that can lead to megaloblastic anaemia?

Answer 3

Low dietary intake e.g. veganism

Pernicious anaemia

Other causes include gastrectomy and congenital deficiency of intrinsic factor

Question 4

What is pernicious anaemia?

Answer 4

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.

Question 5

What are the causes of folate deficiency that can lead to megaloblastic anaemia?

Answer 5

Inadequate intake (found in leafy green vegetables)

Malabsorption

Excess utilisation - haemolysis, exfoliating dermatitis, pregnancy and malignancy.

Drugs - anticonvulsants

Question 6

Apart from folate deficiency and vitamin B12 deficiency, what are other causes of megaloblastic anaemia?

Answer 6

Drugs

Rare inherited abnormalities

Question 7

What is a megaloblast?

Answer 7

An abnormally large nucleated red cell precursor with an immature nucleus

Question 8

What are megaloblastic anaemias characterised by?

Answer 8

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

Question 9

What is the food source for vitamin B12?

Answer 9

Animal

Question 10

How long does the body store vitamin B12 for?

Answer 10

2-4 years

Question 11

Where in the body is vitamin B12 absorbed?

Answer 11

Ileum

Question 12

What is the daily requirement for vitamin B12?

Answer 12

1.5 micrograms/day

Question 13

What is the food source for folate?

Answer 13

Liver, leafy vegetables and fortified cereals

Question 14

How long does the body store folate for?

Answer 14

4 months

Question 15

Where in the body is folate absorbed?

Answer 15

Duodenum and jejunum

Question 16

What is the daily requirement for folate?

Answer 16

200 micrograms/day

Question 17

Clinical features of B12/folate deficiency?

Answer 17

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.

Question 18

Investigations for macrocytic anaemia?

Answer 18

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)

Question 19

Management of macrocytic anaemia?

Answer 19

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

Question 20

What is the mean corpuscular volume (MCV)?

Answer 20

The mean corpuscular volume (MCV) is the measure of the average red blood cell size.

Question 21

What is the difference between microcytic and macrocytic anaemia?

Answer 21

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

Question 22

Difference between sensitivity and specificity?

Answer 22

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.