megaloblastic anaemia

Question 1

what is a megaloblast

Answer 1

an abnormally large nucleated red cell precursor with an immature nucleus. It is a defect in the precursor cells to become smaller rather than an increase in cell size that causes the macrocytes

Question 2

what is it?

Answer 2

a genuine macrocytosis
characterised by a lack of red cells due to predominant defects in DNA synthesis and nuclear maturation in developing precursor cells (megaloblasts) in the marrow

Question 3

pathophysiology

Answer 3

maturing megaloblast division is reduced and apoptosis increases - fewer macrocytes and anaemia

Question 4

what causes it?

Answer 4

B12 deficiency (absorbed in the ileum) 
folate deficiency (absorbed in the jejunum diffusion and actively)
rarer but could be drug effect or genetic disorder

Question 5

what causes folate deficiency?

Answer 5

o Inadequate intake more likely than B12 due to lesser stores 
o malabsorption – coeliac or crohn’s 
o Excess utilisation 
- Haemolysis 
- Exfoliating dermatitis 
- Pregnancy 
- Malignancy

Question 6

how do B12 and folate deficiencies present?

Answer 6

Both 
• Symptoms/signs of anaemia 
• Weight loss, diarrhoea, infertility 
• Sore tongue, jaundice 
• Developmental problems 
With B12 
• Neurological problems – posterior/dorsal column abnormalities, neuropathy, dementia, psychiatric manifestations

Question 7

how is it diagnosed?

Answer 7

Macrocytic anaemia (red cell count is low)
Pancytopenia (all cells low) in some patients
Blood film shows macrovalocytes and hypersegmented neutrophils (normally 3-5 nuclear segments)
Assay B12 and folate levels in serum - Flaws low levels may not always indicate deficiency, normal levels may not always indicate normalcy
Check for autoantibodies
o Antigastric parietal cell (GPC) – flaw, sensitive, not specific
o Anti-intrinsic factor (IF) – flaw, specific, not sensitive
Bone marrow – not usually examined

Question 8

how is it treated?

Answer 8

Treat cause when possible
Vit B12 injections for life in pernicious anaemia
Folic acid tablets (5mg per day) orally
Only if potentially life-threatening anaemia – transfuse red cells

Question 9

what is pernicious anaemia

Answer 9

An autoimmune condition with resulting destruction of gastric parietal cells
Results in intrinsic factor deficiency with B12 malabsorption and deficiency

Question 10

who gets pernicious anaemia?

Answer 10

Associated with atrophic gastritis and personal or family history of other autoimmune disorders

Question 11

how does pernicious anaemia present?

Answer 11

Patients with pernicious anaemia can appear mildly jaundiced due to intramedullary haemolysis