Macrocytic anaemia

Question 1

What is it?

Answer 1

Abnormally large RBCs

Question 2

What are the types/causes? 9

Answer 2

1. Megaloblastic (B12/folate deficiency)
2. Pernicious
3. Bone marrow damage
4. Alcohol abuse
5. Liver disease
6. Hypothyroid
7. Reticulocytosis
8. Other blood disorders (myeloid leukaemia, aplastic anaemia)
9. Drugs that affect DNA synth e.g. azathioprine

Question 3

What are megaloblasts? Why do they form in megaloblastic anaemia?

Answer 3

Immature, large RBCs due to impaired DNA synthesis.

Question 4

Why does B12 or folate deficiency result in megaloblastic anaemia?

Answer 4

B12 is responsible for folate generation which is needed for synthesis of purines and pyramidines in DNA synthesis (DNA of normal RBCs)

Question 5

What is the co-factor for B12? Where are its receptors

Answer 5

Intrinsic factor

Terminal ileum

Question 6

What can stop IF absorption?

Answer 6

Terminal ileum resection
Diverticulosis
Tropical sprue
Crohns

Question 7

Where is B12 absorbed?

Answer 7

Gastric parietal cells

Question 8

What can cause B12 deficiency?

Answer 8

Diet

Not enough absorption:

• Gastrectomy
• Pernicious anaemia (autonomic destruction of gastric mucosa- atrophic gastritis with achlorhydria- or intrinsic factor)

Question 9

What can cause folate deficiency?

Answer 9

Poor absorption:

• Tropical sprue
• Coeliac

Diet

• Anorexia
• Alcohol

Increased uptake

• Haemolysis
• Inflammatory disorders
• Pregnancy

Question 10

Other causes of megaloblastic anaemia?

Answer 10

1. Drugs (Hydroxycarbamides and hydroxyurea)
2. Alcohol
3. Haematological malignancy
4. Congenital (transcobalamine deficiency, orotic aciduria)

Question 11

Symptoms and signs of megaloblastic anaemia?

Answer 11

Mild jaundice 
Glossitis/angular stomatitis
Anorexia/weight loss
Sterility
Pancytopenia if severe

Question 12

If B12 deficiency is severe what can it result in?

Answer 12

Subacute combined degeneration of the spinal cord (SACDC)- demyelination of the dorsal and lateral columns and peripheral nerve damage. Presents as peripheral neuropathy numbness, distal weakness, unsteady walking, dementia (so if present with dementia, check B12- a rare reversible cause!!)

Question 13

Treatment of megaloblastic anaemia

Answer 13

Treat cause

Give B12 and folate until B12 deficiency is excluded- folic acid alone shouldn’t be given as this can make the B12 deficiency worse, so give both until you know.

If pernicious anaemia then give B12 3 monthly for life

Folic acid 5mg daily

Question 14

Investigations for megaloblastic anaemia

Answer 14

Blood film
FBC
Serum B12 and folate
BM biopsy if haem disease or malig suspected
LFTs (liver disease, alcohol abuse)
Urinalysis, U+Es, creatinine (diabetes, homocysteinurea)
Coomb’s test to exclude haemolytic anaemia
Thyroid function test (assoc with hypothyroid)