Macrocytic anaemia

Question 1

Causes of macrocytosis

Answer 1

B12 or folate deficiency
Alcohol
Cytotoxics
Myelodysplasia 
Liver disease
Pregnancy
Hypothyroidism
Smoking

Question 2

Vitamin B12 and folate are (blank blank) vitamins. They are found in…?
Are they destroyed by cooking?

Answer 2

Water soluble
B12 - meat, eggs, animal protein, not destroyed by cooking
Folate - liver, greens, yeast, destroyed by cooking

Question 3

B12 is absorbed in?

Answer 3

Binds to intrinsic factor (produced by parietal cells of gastric mucosa) and is absorbed in the ileum epithelial cells

Question 4

Folate is absorbed in?

Answer 4

Duodenum and proximal jejunum

Question 5

What is a megaloblast?

Answer 5

A cell in which nuclear maturation is delayed compared with the cytoplasm

The cells are large, structurally abnormal, immature RBCs.

Vitamin B12 & folate are needed for DNA synthesis to convert homocysteine into methionine. If deficient, then DNA synthesis is impaired, cells fail to divide, leading to overlarge blood cells.

Question 6

Effect of vitamin B12 or folate deficiency or inhibition on DNA synthesis

Answer 6

B12 and folate are needed for DNA synthesis to convert homocysteine into methionine
If deficient, then DNA synthesis is impaired, cells fail to divide, leading to overlarge blood cells.

Question 7

Causes of vitamin B12 deficiency

Answer 7

Nutritional e.g. poor diet
Malabsorption e.g. pernicious anaemia (absence of intrinsic factor), surgical gastrectomy, ileal disease, drugs e.g. colchicine, metformin, PPIs

Question 8

Causes of folate deficiency

Answer 8

• Nutritional – poor diet
• Malabsorption – coeliac, Crohn’s
• Excess utilization – pregnancy, lactation, haemolytic anaemias, malignancy, inflammatory disease
• Others – anticonvulsants (phenytoin, valproate), methotrexate, trimethoprim
+ LIVER DISEASE

Question 9

Questions on history-taking to elucidate likely causes

Answer 9

• Past medical history - e.g. inflammatory conditions, previous surgery
• Drug history – hydroxycarbamide, phenytoin, valproate, methotrexate, trimethoprim
• Social history - ask about diet, alcohol intake
• Review of systems - symptoms of coeliac or Crohn’s (diarrhoea, constipation, abdominal pain, bloating, weight loss, fatigue), symptoms of malignancy (e.g. weight loss), history of pregnancy/breast-feeding

Question 10

Symptoms of macrocytic anaemia

Answer 10

Cognitive changes. 
Dyspnoea. 
Headache.
Indigestion.
Loss of appetite.
Palpitations.
Tachypnoea.
Visual disturbance. 
Weakness, lethargy.

Question 11

Signs of macrocytic anaemia

Answer 11

Anorexia.
Angina (in older people).
Angular cheilosis.
Brown pigmentation affecting nail beds and skin creases (but not mucous membranes).
Congestive heart failure (in older people).
Episodic diarrhoea.
Glossitis — red smooth and shiny tongue, perhaps with ulcers.
Heart murmurs.
Liver enlargement.
Mild jaundice — a lemon-yellow tint.
Mild pyrexia.
Oropharyngeal ulceration.
Pallor of mucous membranes or nail beds.
Tachycardia.
Weight loss.

Question 12

How much storage of B12 in the body?

Answer 12

2-5mg

About 2-5 years worth

Question 13

How much storage of folate in the body?

Answer 13

10-12mg

About 4 months worth

Question 14

Neurological complications associated with vitamin B12 def

Answer 14

Loss of cutaneous sensation.
Loss of mental and physical drive.
Muscle weakness.
Optic neuropathy.
Psychiatric disturbances – these range from mild neurosis to severe dementia.
Symmetrical neuropathy affecting the legs more than the arms — this usually presents with ataxia or paraesthesia.
Urinary or faecal incontinence.

Question 15

Investigations

Answer 15

FBC - MCV (>100 femtolitres), haematocrit, Hb, WBC and platelets (reduced)
Blood film
Serum cobalamin and folate levels (+ anti-intrinsic factor abs)
LFTs
GGT
TFTs

Question 16

Blood film findings

Answer 16

Hypersegmented neutrophils
Oval macrocytes
Circulating megaloblasts

Question 17

Management of folate deficiency anaemia

Answer 17

Oral folic acid 5 mg daily (usually for 4 months)
Check vitamin B12 levels — treatment can improve wellbeing, mask underlying B12 deficiency, and allow neurological disease to develop.
Give dietary advice
FBC and reticulocyte 7-10 days after starting treatment and after completion
Iron and folate levels after 8 weeks

Question 18

Dietary sources of folic acid

Answer 18

Asparagus.
Broccoli.
Brown rice.
Brussels sprouts.
Chickpeas.
Peas.

Question 19

Management of vitamin B12 deficiency with NO neuro involvement

Answer 19

Initially - Vit B12 IM 3x a week for 2 weeks
If not diet related, give injection every 3 months for life.
If diet related - take tablets daily between meals, or have a twice-yearly injection.
Give dietary advice
FBC and reticulocyte 7-10 days after starting treatment
Iron and folate levels after 8 weeks

Question 20

Dietary sources of B12

Answer 20

Eggs.
Fortified foods - e.g. cereal, bread 
Meat.
Milk and other dairy products.
Salmon and cod.

Question 21

Management of vitamin B12 deficiency with neuro involvement

Answer 21

Seek urgent specialist advice from a haematologist