Macrocytic Anaemia

Question 1

Define macrocytosis:

Answer 1

An increase in abnormally large red blood cells

Question 2

Define macrocytic anaemia:

Answer 2

Anaemia (low Hb) in which the RBCs have a larger than normal blood volume

Question 3

What blood measurement shows macrocytosis?

Answer 3

MCV

Question 4

Megaloblastic causes of anaemia affect what part of the cell development?

Answer 4

DNA synthesis and gene production

Question 5

What would the blood measurements in macrocytosis look like?

Answer 5

Normal Hb
Normal RBC
High MCV

Question 6

What would the blood measurements in macrocytic anaemia look like?

Answer 6

Low Hb

High MCV

Question 7

On a blood film, what can be used to compare the size of RBCs?

Answer 7

A RBC should be roughly the same size as the nucleus of a lymphocyte

Question 8

What are the two main, genuine causes of macrocytosis?

Answer 8

Megaloblastic

Non-megaloblastic

Question 9

When do early erythrocytes lose their nuclei?

Answer 9

Once they have reached maximum Hb levels

Question 10

What happens in ineffective erythropoiesis?

Answer 10

RBCs die prematurely in the bone marrow. The dead cells then release LDH and Hb (which is broken down into bilirubin)

Question 11

What is a megaloblast?

Answer 11

This is an abnormally large RBC which still has a nucleus

Question 12

What are the main causes of megaloblastic anaemia?

Answer 12

B12 deficiency
Folate deficiency
Drugs
Rare inherited conditions

Question 13

What cycle is B12 involved in?

Answer 13

The methionine cycle

Question 14

What important function is the folate cycle involved in?

Answer 14

Converts uridine to thymidine

Question 15

What are B12 and Folate mainly responsible for?

Answer 15

They are important co-factors in the nuclear maturation of the erythrocyte via DNA synthesis

Question 16

What is released from gastric parietal cells which plays an important role in the absorption of B12?

Answer 16

Intrinsic Factor

Question 17

What binds to B12 in the stomach to aid its absorption process?

Answer 17

R-protein

Question 18

Where is B12 absorbed in the GI tract?

Answer 18

Terminal end of the small bowel (i.e. ileum)

Question 19

What can cause B12 deficiency?

Answer 19

PPIs
Bacterial overgrowth in GI tract
Poor diet
Malabsorption e.g. coeliac, IBD
Atrophic Gastritis 
Pernicious Anaemia

Question 20

Define pernicious anaemia:

Answer 20

This is an autoimmune disease which involves the destruction of gastric parietal cells, leading to decreased intrinsic factor therefore causing decreased B12 levels.

Question 21

What other diseases are associated with pernicious anaemia?

Answer 21

Hypothyroid
Addison’s
Vitiligo

Question 22

Dietary folates are converted to __________?

Answer 22

Monoglutamates

Question 23

Where are monoglutamates absorbed in the GI tract?

Answer 23

Jejunum

Question 24

What can cause a folate deficiency?

Answer 24

Decreased intake (diet)
Drugs e.g. anti-convulsant
Malabsorption
Excess utilisation of folate e.g. haemolysis, pregnancy, exfoliating dermatitis, malignancy

Question 25

List some clinical features of B12/Folate deficiency:

Answer 25

``` Signs/symptoms of anaemia Weight loss Jaundice Sore (beefy) tongue Diarrhoea Development problems ```

Question 26

What symptoms are specifically associated with B12 deficiency and why?

Answer 26

Neurological problems -> lack of B12 can lead to demyelination e.g. dementia, neuropathy, psychiatric manifestations etc

Question 27

Why is jaundice seen in B12/folate deficiencies?

Answer 27

Intramedullary haemolysis

Question 28

What specific features will be seen on a blood film in B12/folate deficiency?

Answer 28

Macrocytic anaemia Sometimes pancytopenia Hyper segmented neutrophils

Question 29

What anti-bodies might you check for in a B12 deficiency?

Answer 29

Anti-intrinsic factor Anti-gastric parietal cells (to rule out pernicious anaemia)

Question 30

How do you treat pernicious anaemia

Answer 30

Regular life long Vit B12 injections

Question 31

How do you treat folate deficiency?

Answer 31

5mg folate tablets daily

Question 32

Would a patient with macrocytic anaemia ever require a blood transfusion?

Answer 32

Rarely | Only if Hb dropped so low it was absolutely necessary (e.g. below 70)

Question 33

List some causes of non-megaloblastic macrocytosis which may NOT be associated with anaemia?

Answer 33

Alcohol abuse Liver disease Hypothyroidism

Question 34

List some causes of non-megaloblastic macrocytosis, often associated with anaemia?

Answer 34

Marrow failure causes: - myelodysplasia - myeloma - aplastic anaemia

Question 35

Define spurious macrocytosis:

Answer 35

(False macrocytosis) | This is where the mature RBC count is normal BUT there is a high MCV

Question 36

What are the two main causes for spurious macrocytosis?

Answer 36

``` Reticulocytosis Cold agglutinins (clumps of RBCs) ```

Question 37

When does Reticulocytosis tend to occur?

Answer 37

Response to large bleeds / acute bleeds | Increased RBC breakdown

Question 38

What will be seen on a blood film of a patient with Reticulocytosis?

Answer 38

Polychromasia