Macrocytic anaemia

Question 1

What is macrocytic anaemia?

Answer 1

This is an anaemia in which the red cells have an MCV larger than normal volume

Question 2

What are the 2 main classes of macrocytic anaemia?

Answer 2

Genuine macrocytic anaemia
Spurious macrocytic anaemia

Question 3

What are the 2 classes of genuine macrocytic anaemia?

Answer 3

Megaloblastic anaemia
Non-megaloblastic anaemia

Question 4

What is megaloblastic anaemia?

Answer 4

This is form of macrocytic anaemia in which there is a presence of megaloblasts

Question 5

What are megaloblasts?

Answer 5

Megaloblasts are larger than normal, nucleated erythrocyte precursor cells with an immature nucleus, normally based in the bone marrow

Question 6

Describe the pathophysiology of megaloblastic anaemia?

Answer 6

• Defects in DNA synthesis and nuclear maturation
• Reduced cell division and increased apoptosis
• Cytoplasmic development and Hb accumulation occur normally, so precursor cells become larger than normal
• The nucleus is then removed, leading behind a macrocyte

Question 7

What are some causes of megaloblastic anaemia?

Answer 7

• B12 deficiency
• Folate deficiency
• Drugs
• Rare inherited abnormalities

Question 8

What are some causes of non-megaloblastic anaemia?

Answer 8

• Alcohol
• Liver disease
• Hypothyroidism
• Marrow failure

Question 9

What are some possible causes of marrow failure?

Answer 9

Myelodysplasia
Myeloma
Aplastic anaemia

Question 10

What is spurious anaemia?

Answer 10

This is an anaemia in which readings suggest increased cell size, despite cell size being normal

Question 11

What are the 2 main causes of spurious anaemia?

Answer 11

Reticulocytosis
Cold-aglutinins

Question 12

What is reticulocytosis?

Answer 12

Reticulocytosis is an increase in reticulocyte numbers, occurring as a marrow response to acute blood loss or red cell breakdown

Question 13

How can reticulocytosis lead to spurious anaemia?

Answer 13

Reticulocytes are larger than normal red blood cells, so testing methods will show a higher average MCV reading, despite the red cells being of normal size

Question 14

What are cold agglutinins?

Answer 14

Cold-agglutinins are proteins that cause clumping of red cells when samples are taken into the cold

Question 15

How do cold agglutinins lead to spurious anaemia?

Answer 15

Clumping of red cells will cause the analyser to pick up much larger cell volumes, despite the cells themselves within the clumping being of normal size

Question 16

What approach should be taken to diagnosis of cause of macrocytic anaemia?

Answer 16

The first test in suspected macrocytic anaemia is reticulocyte count:

• Raised = Haemorrhage or haemolysis
• Normal/decreased →

Then neutrophils should be examined for hyper-segmented nuclei:

• Yes = Liver disease, hypothyroidism, alcoholism or malignancy
• No →

Finally, serum B12 and folate should be measured:

• High = Malignancy
• Low = Megaloblastic anaemia (Mostly)