Macrocytic anaemia

Question 1

What is the classification of macrocytic anaemia?

Answer 1

Megaloblastic and non-megaloblastic.
Megaloblastic - slow or impaired DNA synthesis. Causing delayed maturition of RBCs and hypersegmented neutrophils.
Non megaloblastic - may have macrocytosis without anaemia

Question 2

What are the causes of megaloblastic anaemia?

Answer 2

1. B12 deficiency,
2. Folate deficiency,
3. Drugs: Hydroxycarbamide, azathioprine

Question 3

What are the causes of non megaloblastic macrocytic anaemia?

Answer 3

Liver disease,
Alcohol,
Hypothyroidism
Myelodysplastic syndrome,
Pregnancy
Reticulocytosis

Question 4

What are the signs and symptoms of macrocytic anaemia?

Answer 4

Fatigue and Weakness,
Pallor,
SOB,
Glossitis and beefy tongue,
Neurological symptoms: severe vitamin B12 deficiency can cause paraesthesia, ataxia and cognitive impairment
Folate def can cause neural tube defects, thrombocytopenia and leucopenia

Question 5

Explain the process of B12 absorption

Answer 5

Proteins are broken down by gastric acid and enzymes to release B12 in the stomach and duodenum. Parietal gastric cells release intrinsic factor which B12 binds too. Once the IF-B12 complex forms it can then bind to cubulin, a receptor in the ileum, and it is then transported into the bloodstream where B12 binds to transcobalamin.

Question 6

What are the causes of a vitamin B12 deficiency?

Answer 6

Pernicious anaemia (most common cause),
Gastrectomy/achlorhydria,
Terminal ileum issues (Crohn’s or resection)
Vegan diet,
Metformin use,
PPI use

Question 7

What is the importance of B12 and folate?

Answer 7

They are essential co-factors for DNA synthesis.
Specifically formation of methionine and tetrahydrofolate. Without these there is ineffective erythropoiesis and death of mature cells leading to raised LDH and billirubin

Question 8

What are some causes of a folate deficiency?

Answer 8

Dietary (main cause)
Small bowel disease such as coeliac’s or Crohns,
Increase cell turn over (haemolysis, severe skin disorders and pregnancy)

Question 9

What are the investigations for macrocytic anaemia?

Answer 9

FBC,
Haematinics,
Blood film: Macrocytosis and hypersegmented neutrophils,
TFTs to look for hypothyroidism,
LFTs to assess liver function,
Antibodies to intrinsic factor,
Markers of heamolysis: LDH, brilirubin

Question 10

What is the management of macrocytic anaemia

Answer 10

Megaloblastic: Pernicious anaemia requires IM hydroxocobalamin. However if deficient in both Vit B12 and folate, must address B12 first. If you replace folate first then may worsen neuro symptom’s and cause subacute degeneration of the spinal cord.
Non-megaloblastic - Treat underlying cause.

Question 11

Explain the treatments for B12 and folate deficiency

Answer 11

B12 - Hydroxocobalamin 1mg IM 3x week for 3 weeks followed by 1mg IM every 3 months for life (if not diet related). If diet related then give oral cyanocobalamin
Folate def - 5mg oral folate per day (treatment required for 4+ months)

Question 12

What is aplastic anaemia?

Answer 12

bone marrow failure resulting in pancytopenia. Can be acquired or inherited. Presents with:
Hb < 10.
Platelets < 50.
Neutrophil count < 1.5