Macrocytic anaemia

Question 1

Define:

Answer 1

• Anaemia associated with a high MCV of erythrocytes (>100 fl in adults)
• Usually results from abnormal haemopoiesis

Question 2

Aetiology:

Answer 2

• Megaloblastic – specifically refers to a delay in maturation of the nucleus while the cytoplasm continues to mature
o Caused by deficiency of B12 or folate

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

Non-Megaloblastic

Question 3

What are the causes of B12 and folate deficiency

Answer 3

o Causes of Vitamin B12 Deficiency:
• Reduced absorption (e.g. post-gastrectomy, pernicious anaemia – autoimmune condition causing severe lack of IF, terminal ileal/small bowel resection or disease)
• Reduced intake (vegans)
• Abnormal metabolism (congenital transcobalamin II deficiency)

Causes of Folate Deficiency:
• Reduced intake (alcoholics, elderly, anorexia)
• Increased demand (pregnancy, lactation, malignancy, chronic inflammation)
• Reduced absorption (coeliac, tropical sprue)
• Jejunal disease (e.g. coeliac disease)
• Drugs (e.g. phenytoin

Question 4

What are non-megaloblastic causes:

Answer 4

o	Alcohol excess or Liver disease – ROUND macrocytes
o	Myelodysplasia
o	Multiple myeloma
o	Hypothyroidism 
o	Aplastic anaemia
o	Haemolysis (shift to immature red cell form - reticulocytosis) 
o	Drugs (e.g. tyrosine kinase inhibitor)
o	Pregnancy

Question 5

Epidemiology:

Answer 5

• More common in ELDERLY FEMALES

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

Question 6

Symptoms:

Answer 6

•	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 7

Signs of anaemia:

Answer 7

o Pallor
o Tachycardia
o Breathlessness

Question 8

Signs of pernicious anaemia:

Answer 8

o Mild jaundice
o Glossitis
o Weight loss

Question 9

Signs of B12 deficiency:

Answer 9

o Peripheral neuropathy
o Ataxia
o Subacute combined degeneration of the spinal cord
o Optic atrophy
o Dementia
o Positive Babinski’s, absent ankle reflex, increase knee reflex

Question 10

Investigations:

Answer 10

o FBC
• High MCV
• Pancytopaenia in megaloblastic anaemia

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 (90%) and anti-intrinsic factor antibodies (40-60%)
o Serum protein electrophoresis - looking for a dense band in myeloma
• Blood Film
o Large erythrocytes

o In megaloblastic anaemia: (Megaloblasts, Hypersegmented neutrophil nuclei, Target cells if liver disease

Schilling Test (Method of testing for pernicious anaemia , B12 will only be absorbed when given with intrinsic factor
• Bone Marrow Biopsy (rarely needed) – if cause not identified
• Investigations for the cause

Question 11

Management:

Answer 11

• Pernicious Anaemia
o IM hydroxycobalamin for life
o If no neurological defect
 IM hydroxycobalamin 1mg 3x/week for 2 weeks then 1mg/3 months
o If neurological defect present
 1mg every other day until no further improvement then 1mg/2 months
• B12 deficiency
o Dietary supplements – PO cyanocobalamin
• Folate Deficiency
o Oral folic acid
o If B12 deficiency is present, it must be treated before the folic acid deficiency as B12 is needed for folate to enter cells
• In pregnancy, prophylactic folate is given from conception until 12 weeks to prevent spina bifida

Question 12

Complications:

Answer 12

• Pernicious anaemia –> increased risk of gastric cancer

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

Question 13

Prognosis:

Answer 13

• Majority are treatable if there are no complications