Macrocytic Anaemia

Question 1

What is Macroctyic Anaemia?

Answer 1

large Mean Corpuscular Volume indicating large RBCs

Question 2

What is the normal range of MCV?

Answer 2

80-100 femtolitres

Question 3

Macrocytic anaemia can be divided into what two categories?

Answer 3

megaloblastic bone marrow and those with a normoblastic bone marrow

Question 4

How does megaloblastic anaemia arise?

Answer 4

impaired DNA synthesis preventing the cell from deciding normally
Rather than dividing it keeps growing into a larger, abnormal cell

Question 5

What are megaloblastic causes?

Answer 5

vitamin B12 deficiency

folate deficiency

Question 6

What are normoblastic causes?

Answer 6

alcohol
liver disease
hypothyroidism
drugs: cytotoxics

pregnancy
reticulocytosis (from hemolytic anaemia or blood loss)
myelodysplasia

Question 7

Vitamin B12 is mainly used in the body for?

Answer 7

red blood cell development and also maintenance of the nervous system

Question 8

How is Vitamin B12 absorbed?

Answer 8

It is absorbed after binding to intrinsic factor (secreted from parietal cells in the stomach)
is actively absorbed in the terminal ileum

Question 9

A small amount of vitamin B12 is passively absorbed without being bound to intrinsic factor.

Answer 9

true

Question 10

Causes of vitamin B12 deficiency?

Answer 10

pernicious anaemia: most common cause
vegan diet or a poor diet

post gastrectomy
disorders/surgery of terminal ileum
Crohn’s: either diease activity or following ileocaecal resection

metformin (rare)

Question 11

What type of anaemia do you get in B12 deficit?

Answer 11

macrocytic anaemia

Question 12

What symptoms do you get in B12 deficiency?

Answer 12

sore tongue and mouth

neurological symptoms
the dorsal column is usually affected first (joint position, vibration) prior to distal paraesthesia

neuropsychiatric symptoms: e.g. mood disturbances

Question 13

What factors determine management in B12 deficiency:?

Answer 13

neurological involvement

if a patient is also deficient in folic acid

Question 14

Outline management of B12 deficiency?

Answer 14

if no neurological involvement 1 mg of IM hydroxocobalamin 3 times each week for 2 weeks

then once every 3 months

if a patient is also deficient in folic acid then it is important to treat the B12 deficiency first to avoid precipitating subacute combined degeneration of the cord

Question 15

What should you do in B12 deficiency with neurological involvement

Answer 15

Seek urgent specialist advice from a hematologist.

if specialist advice is not immediately available, consider the following:

Initially administer hydroxocobalamin 1 mg intramuscularly on alternate days until there is no further improvement

then administer hydroxocobalamin 1 mg intramuscularly every 2 months.

Question 16

What is Pernicious Anaemia?

Answer 16

autoimmune disorder affecting the gastric mucosa that results in vitamin B12 deficiency.

Question 17

What does pernicious mean

Answer 17

pernicious means ‘causing harm, especially in a gradual or subtle way’ - the symptoms of signs are often subtle and diagnose is often delayed.

Question 18

Is pernicious anaemia the commonest cause of B12 deficit?

Answer 18

YES

Question 19

Is pernicious anaemia the ONLY cause of B12 deficit?

Answer 19

NO
Other causes include atrophic gastritis (e.g. secondary to H. pylori infection), gastrectomy, malnutrition (e.g. alcoholism).

Question 20

What antibodies are assoc with pernicious anaemia?

Answer 20

antibodies to intrinsic factor +/- gastric parietal cells

Question 21

What do intrinsic factor antibodies do?

Answer 21

bind to intrinsic factor blocking the vitamin B12 binding site

Question 22

What do gastric parietal antibodies do?

Answer 22

Cause reduced acid production and atrophic gastritis

Cause reduced intrinsic factor production → reduced vitamin B12 absorption

Question 23

vitamin B12 is important in both the production of blood cells and the myelination of nerves

Answer 23

true

→ megaloblastic anaemia and neuropathy

Question 24

Describe the aetiology of Pernicious anaemia

Answer 24

more common in females (F:M = 1.6:1)
typically develops in middle to old age
more common if blood group A

associated with other autoimmune disorders: thyroid disease, type 1 diabetes mellitus, Addison’s, rheumatoid and vitiligo

Question 25

List the neurological features that may arise with PA

Answer 25

peripheral neuropathy: ‘pins and needles’, numbness. Typically symmetrical and affects the legs more than the arms

subacute combined degeneration of the spinal cord: progressive weakness, ataxia and paresthesias that may progress to spasticity and paraplegia

neuropsychiatric features: memory loss, poor concentration, confusion, depression, irritabiltiy

Question 26

List the symptoms of PA (other than neurological)

Answer 26

anaemia features: lethargy, pallor, dyspnoea
mild jaundice: combined with pallor results in a ‘lemon tinge’
glossitis → sore tongue

Question 27

Schilling test is the diagnostic test for PA

Answer 27

False

Schilling test is no longer routinely done

Question 28

What tests should you do for PA?

Answer 28

full blood count
vitamin B12 and folate levels
antibodies

Question 29

What would FBC show in PA?

Answer 29

macrocytic anaemia
macrocytosis may be absent in around of 30% of patients
low WCC and platelets may also be seen

Question 30

What would blood film show in PA?

Answer 30

hypersegmented polymorphs on blood film

Question 31

a vitamin B12 level of what is generally considered to be normal

Answer 31

> = 200 nh/L

Question 32

Describe the sensitivity and specifiity of anti intrinsic factor antibodies for PA

Answer 32

sensivity is only 50% but highly specific for pernicious anaemia (95-100%)

Question 33

Is gastric parietal cell antibodies useful in diagnosing PA? why?

Answer 33

anti gastric parietal cell antibodies in 90% but low specificity so often not useful clinically

Question 34

Outline the managemet of PA

Answer 34

vitamin B12 replacement
usually given intramuscularly
no neurological features: 3 injections per week for 2 weeks

followed by 3 monthly treatment of vitamin B12 injections

more frequent doses are given for patients with neurological features

folic acid supplementation may also be required

Question 35

People with PA have an increased risk of what?

Answer 35

increased risk of gastric cancer

Question 36

What is Myelodysplastic syndrome?

Answer 36

acquired neoplastic disorder of hematopoietic stem cells

Question 37

What is the sequelae of Myelodysplastic syndrome?

Answer 37

pre-leukaemia, may progress to AML

Question 38

Myelodysplastic syndrome is more common with age

Answer 38

YES

Question 39

How would Myelodysplastic syndrome present?

Answer 39

presents with bone marrow failure (anaemia, neutropaenia, thrombocytopenia)