Macrocytic Anaemia

Question 1

Definition

Answer 1

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

Question 2

Aetiology (megaloblastic)

Answer 2

• Megaloblastic - when the bone marrow produces unusually large, structurally abnormal, immature red cells
o Caused by deficiency of B12 or FOLATE required for the conversion of deoxyuridate to thymidylate, DNA synthesis and nuclear maturation

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

Question 3

Aetiology (causes of B12 deficiency)

Answer 3

• Reduced absorption (e.g. post-gastrectomy, pernicious anaemia (autoimmune cause leading to anti-IF antibodies?) terminal ileal resection or disease (classically Crohn’s disease affects the terminal ileum so can lead to b12 deficiency))
• Reduced intake (vegans)
• Abnormal metabolism (congenital transcobalamin II deficiency)

Question 4

Aetiology (causes of folate deficiency)

Answer 4

• Reduced intake (alcoholics, elderly, anorexia)
• Increased demand (pregnancy, lactation, malignancy, chronic inflammation)
• Reduced absorption
• Jejunal disease (e.g. coeliac disease!! - folic acid is absorbed in the jejunum)
• Drugs (e.g. phenytoin)

Question 5

Aetiology (non-megaloblastic/normoblastic)

Answer 5

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

Question 6

Epidemiology

Answer 6

• More common in ELDERLY FEMALES

* Pernicious anaemia is the MOST COMMON cause of B12 deficiency in the West

Question 7

Presenting symptoms

Answer 7

• Non-specific symptoms of anaemia:
o Tiredness
o Lethargy
o Dyspnoea

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

Question 8

Signs on physical examination (anaemia)

Answer 8

o Pallor
o Tachycardia
o Breathlessness

Question 9

Signs on physical examination (pernicious anaemia)

Answer 9

o Mild jaundice
o Glossitis
o Angular stomatitis
o Weight loss

Question 10

Signs on physical examination (B12 deficiency)

Answer 10

o Peripheral neuropathy
o Ataxia
o Subacute combined degeneration of the spinal cord
o Optic atrophy
o Dementia

Question 11

Investigations (bloods)

Answer 11

o FBC
• High MCV
• Pancytopaenia in megaloblastic anaemia
• Different degrees of cytopaenia in myelodysplasia
• Exclude reticulocytosis

o LFT
• High bilirubin (due to ineffective erythropoiesis or haemolysis)

o ESR
o TFT
o Serum vitamin B12
o Red cell folate
o Anti-parietal cell and anti-intrinsic factor antibodies
o Serum protein electrophoresis - looking for a dense band in myeloma

Question 12

Investigations (other)

Answer 12

• Blood Film
o Large erythrocytes
o In megaloblastic anaemia:
• Megaloblasts
• Hypersegmented neutrophil nuclei

• Schilling Test
o Method of testing for pernicious anaemia
o B12 will only be absorbed when given with intrinsic factor

• Bone Marrow Biopsy (rarely needed)
• Investigations for the cause

Question 13

Management plan

Answer 13

• Pernicious Anaemia
o IM hydroxycobalamin for life

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

Question 14

Possible complications

Answer 14

• Pernicious anaemia –> increased risk of gastric cancer

* Pregnancy - folate deficiency increases the risk of neural tube defects

Question 15

Prognosis

Answer 15

• Majority are treatable if there are no complications

Question 16

Pernicious anaemia

Answer 16

Lack intrinsic factor
Stop absorbing b12
DNA replicates poorly
Thus cell grows but fails to divide
Macrocytosis results from vitamin b12 and folate deficiency
Hypersegmented neutrophils is a feature of pernicious anaemia

Question 17

Mneumonic for causes

Answer 17

Alcoholics May Have Liver Failure

Alcohol
Myelodysplasia
Hypothyroidism
Liver disease 
Folate/B12 deficiency