1. Macrocytic
Anaemia
Prof. Rafi Ahmed Ghori
FCPS
Professor & Chairman Medicine
Liaquat University of Medical & Health
Sciences, Jamshoro

2. Red Cell Indices
• Mean cell volume (MCV)
• Mean cell Hb concentration (MCHC)
• Red cell distribution width (RDW)

3. Mean Cell Volume
(Normal 80 - 100 fL)
• Low MCV = Microcytic
• Normal MCV = Normocytic
• High MCV = Macrocytic

4. Mean Cell Hemoglobin Concentration
(Normal 32-36 g/dL)
• Low MCHC = hypochromic
• Normal MCHC = normochromic
• High MCHC = hyperchromic

5. Decreased Production Anemia
Macrocytic
• Megaloblastic anemia

6. Megaloblastic Anemia
• Definition
– anemia or pancytopenia caused by
impaired DNA synthesis
– deficiency of vitamin B12 or folic
acid

7. Vitamin B12 Deficiency
• Cobalamin.
• Exclusive source is dietary animal
products.
• 2mg to 3mg per day.
• 70% is absorbed.
• Stores are 5000mg.
• Present mostly in liver, kidney and heart
which is enough for several years.

10. Aetiology
• Inadequate diet.
• Impaired absorption.
• Increased requirements.

11. Aetiology
• Inadequate dietary intake
– Vegans.
• Impaired absorption
– Stomach
• Pernicious anaemia.
• Gastrectomy.
• Congenital deficiency of intrinsic factor.
– Small bowel
– Ileal disease or resection
– Bacterial overgrowth.
– Tropical sprue.
– Fish tapeworm.

12. Aetiology
• Abnormal metabolism
– Congenital transcobalamin II deficiency.
– Nitrous oxide (inactivates B12).

13. Megaloblastic Anaemia
• Defective DNA synthesis and normal
RNA/protein synthesis.
• Rapidly proliferating cells are affected.
• Ineffective haematopoiesis

14. Clinical Features
• Insidious onset.
• Progressive increase in symptoms of
anaemia.
• Patient may look lemon-yellow colour.
• Mild jaundice.
• Red sore tongue (glossitis) and angular
stomatitis.

16. Clinical Features
• Neurological changes, if left untreated,
can be irreversible.
• Polyneuropathy involving peripheral
nerve, posterior and lateral column of
spinal cord (subacute combined
degeneration).
• Patient feels symmetrical paraesthesiae
in fingers and toes, loss of posterior
column sensation.

17. Clinical Features
• Progressive weakness and ataxia.
• Paraplagia.
• Dementia and optic atrophy.

18. Diagnostic Features
• Haemoglobin
– often reduced, may be very low.
• Mean cell volume
– usually raised, commonly > 120 fl.
• Erythrocyte count
– low for degree of anaemia.

19. Diagnostic Features
• Blood film
– oval macrocytosis.
– poikilocytosis.
– red cell fragmentation.
– neutrophil hypersegmentation.
• Reticulocyte count
– low for degree of anaemia.
• Leucocyte count
– low or norma.
• Platelet count
– low or normal.

28. Diagnostic Features
• Bone marrow
– increased cellularity.
– megaloblastic changes in erythroid series.
– giant metamyelocytes.
– dysplastic megakaryocytes.
– increased iron in stores.
– pathological non-ring sideroblasts.

30. Diagnostic Features
• Serum iron
– elevated.
• Iron-binding capacity
– increased saturation.
• Serum ferritin
– elevated.
• Plasma LDH
– elevated, often markedly.

31. Diagnosis of B12 Deficiency
Anaemia
• Normal and high MCV, high RDW.
• Triad
– Macroovalocytes.
– Howell-Jolly bodies.
– Hypersegmented neutrophils.

32. Pernicious Anaemia
• Lack of intrinsic factor.
• Most important and common cause of
B12 deficiency.
• 90% patients have antiparietal cell
antibodies – not specific.

33. Pernicious Anaemia
• Laboratory findings
– Features of B12 deficiency.
– Auto antibodies (anti-IF, antiparietal
antibodies).
– Achlorhydria.
– Positive Schilling test.
• IM injection of B12.

35. Schilling test
• Helps determine the aetiology of
megaloblastic anaemia.
• Dietary deficiency, absence of IF or
malabsorption.
• Patient is given radioactive labelled B12
orally followed within 2 hours by an IM
injection of unlabeled B12.
• Urine is collected for 24 hours and the
radioactivity of the urine is determined.

36. Schilling test
• <7.5% excretion – Pernicious anaemia
and malabsorption.
• If excretion is <7.5%, oral doses of B12
and IF given.
• >7.5% excretion – Pernicious anaemia.
• <7.5% excretion – malabsorption defect.

37. Folate Deficiency
• Same characteristics as in vitamin B12
deficiency.
• However, neurological changes seen in
vitamin B12 deficiency do not occur.
• Pteroylglutamic acid.
• Green leafy vegetables, egg, mild, yeast,
liver, micro-organisms.

38. Folate Deficiency
• Destroyed by heat.
• 200mg/day.
• 50-70% absorbed from proximal ileum.
• Stored in liver (5-10 mg), which is good
for 3-6 months.

40. Folate Deficiency
• Decreased intake.
• Increased requirements.
• Malabsorption.
• Impaired utilisation.

41. Folate Deficiency
• Laboratory findings
– Normal or high MCV, high RDW.
– Features of ineffective erythropoiesis (increased
indirect bilirubin, increased LDH).
– Low serum and red cell folate.
– Increased urinary excretion of foriminoglutamic
acid (FIGLU).
– Therapeutic doses of folate can partially correct
B12 deficiency anaemia but no effect on
neurological manifestations.

42. Folate Deficiency
• Both serum and red cell folate levels
must be decreased to diagnose folate
deficiency.
• Red cell folate is a better indication of
folate stores.
• Low serum folate usually indicates an
imminent folic acid deficiency and
precedes red cell folate deficiency.

43. Folate Deficiency
• Cobalamin is necessary to keep the
conjugated form of folate within the
cells.
• Neither serum nor red cell folate is a
good indicator of folate stores in the
presence of cobalamin deficiency.
• Serum folate may be falsely increased
and red cell folate falsely decreased in
cobalamin deficiency.

45. Treatment
• B12 deficiency
– Hydrocobalamin 1000-µg IM (total 5-6 mg)
during first-three weeks.
– Hydrocobalamin 1000-µg every three
months (may be for lifelong).
– Treat the underlying cause if possible.

46. Treatment
• Folate deficiency
– Folic acid (5-mg) daily for 4 months.
– Prophylactic folic acid (400-µg daily) for
pregnant women is recommended.

47. Macrocytic Anaemia without
Megaloblastosis
• High MCV, Normal RDW, round
macrocytes, absence of hypersegmented
neutrophils.

48. Macrocytic Anaemia without
Megaloblastosis
• Alcoholism.
• Liver disease.
• Myelodysplastic syndrome.
• Hypothyroidism.
• Aplastic anaemia.
• Drugs.

49. Investigation of macrocytic anaemia
High MCV / MCH
Blood film
Reticulocyte count
High
Acute blood
loss
Haemolytic
anaemia
Normal / low
Bone marrow
morphology
Non-megaloblastic
Normoblastic
Alcoholic liver
disease, Hypothyroid
Dyserythropoietic
Myelodysplasia
Megaloblastic Folate and B12
Folate low
Folate
deficiency
B12 low
B12
deficiency

50. Thanks