Macrocytic anaemia

Question 1

Define

Answer 1

anaemia associated with a high MCV of erythrocytes (> 100 fl in adults)

Question 2

Cause

Answer 2

Megaloblastic - when the bone marrow produces unusually large, structurally abnormal, immature red cells

Caused by deficiency of B12 or folate required for the conversion of deoxyuridate to thymidylate, DNA synthesis and nuclear maturation

Causes of Vitamin B12 Deficiency:

1. Reduced absorption (e.g. post-gastrectomy, pernicious anaemia, terminal ileal resection or disease)
2. Reduced intake (vegans)
3. Abnormal metabolism (congenital transcobalamin II deficiency)

Causes of Folate Deficiency:

1. Reduced intake (alcoholics, elderly, anorexia)
2. Increased demand (pregnancy, lactation, malignancy, chronic inflammation)
3. Reduced absorption
4. Jejunal disease (e.g. coeliac disease)
5. Drugs (e.g. phenytoin)

Drugs

• Methotrexate (dihydrofolate reductase inhibitor)
• Hydroxyurea
• Azathioprine
• Zidovudine

Non-Megaloblastic

• Alcohol excess
• Liver disease
• Myelodysplasia
• Multiple myeloma
• Hypothyroidism
• Haemolysis (shift to immature red cell form - reticulocytosis)
• Drugs (e.g. tyrosine kinase inhibitor)

Question 3

Epidemiology

Answer 3

elderly and females
Pernicious anaemia is most common cause of B12 deficiency in West

Question 4

Symptoms

Answer 4

Non-specific symptoms of anaemia:

• Tiredness
• Lethargy
• Dyspnoea
• Family history of autoimmune disease
• Previous GI surgery
• Symptoms of the CAUSE (e.g. weight loss, diarrhoea)

Question 5

Signs

Answer 5

• Anaemia: pallor, tachycardia, signs of cause

(malnutrition, jaundice, hypothyroid)

• Pernicious anaemia: lemon-tinted skin (mild jaundice),

glossitis, angular stomatitis, ↓weight

• B12 deficiency: peripheral neuropathy, ataxia, subacute

combined degeneration of the SC, optic atrophy, dementia

Question 6

Investigations

Answer 6

Blood – FBC (↑MCV, pancytopenia in megaloblastic)
LFT (↑ bilirubin from ineffective erythropoiesis/haemolysis) ESR, TFT, B12, RC folate, antibodies against IF/parietal cells

Blood film – large erythrocytes (macrocytes)
In megaloblastic → macroovalocytes, hypersegmented neutrophil nuclei (>5 lobes)

Schilling’s test:

Part I: radiolabelled vit B12 given orally and IM non-radioactive B12 given to saturate vitamin B12-binding proteins. •Radiolabelled B12 in a 24hr urine collection indicates absorption Part II: Part I repeated with oral IF – if radiolabelled vitamin B12 is now detected in urine, the cause is likely to be IF deficiency from pernicious anaemia

Question 7

Management

Answer 7

Pernicious Anaemia

• IM hydroxycobalamin for life

Folate Deficiency

• Oral folic acid
• If B12 deficiency is present, it must be treated before the folic acid deficiency

Question 8

Complications

Answer 8

Pernicious anaemia –> increased risk of gastric cancer

Pregnancy - folate deficiency increases the risk of neural tube defects

Question 9

Prognosis

Answer 9

Majority are treatable if there are no complications