Megaloblastic Anemia

1. MEGALOBLASTIC
ANEMIA
Dr. Sookun Rajeev K
(MD)
Dept of General Medicine
Anna Medical College

2. DEFINITION:
Megaloblastic anemia is associated with an
abnormal appearance of the bone marrow
erythroblasts in which nuclear development is
delayed and nuclear chromatin has a lacy open
appearance.
There is a defect in DNA synthesis usually
caused by deficiency of Vit B12 or folate

3. CAUSES OF MEGALOBLASTIC ANEMIA
Diet
•Vitamin B12 deficiency: vegan diet,
poor quality diet
•Folate deficiency: poor quality diet,
old age, poverty, synthetic diet
without added folic acid, goats’ milk

4. CAUSES OF MEGALOBLASTIC ANEMIA
Malabsorption
•Gastric causes of vitamin B12 deficiency: pernicious
anaemia, congenital intrinsic factor deficiency or
abnormality, gastrectomy
•Intestinal causes of vitamin B12 deficiency: stagnant
loop, congenital selective malabsorption, ileal
resection, Crohn’s disease
•Intestinal causes of folate deficiency: coeliac
disease, tropical sprue, jejunal resection

5. CAUSES OF MEGALOBLASTIC ANEMIA
Increased cell turnover
•Folate deficiency: pregnancy, prematurity,
chronic haemolytic anemia (such as sickle
cell anemia), extensive inflammatory and
malignant diseases

6. CAUSES OF MEGALOBLASTIC ANEMIA
Renal loss
•Folate deficiency: congestive cardiac
failure, dialysis
Drugs
•Folate deficiency: anticonvulsants,
sulphasalazine

7. CLINICAL MANIFESTATIONS OF VIT B12 DEFICIENCY
•The manifestations appear after deficiency of
vitamin B12 has been present for 3-12 years.
•There is pallor of skin and mucous membranes.

8. CLINICAL MANIFESTATIONS OF VIT B12 DEFICIENCY
•The skin shows a lemon yellow tint due to mild
jaundice.
•The tongue is smooth, atrophic, red and raw with
loss of papillae and there is angular stomatitis.

9. CLINICAL MANIFESTATIONS OF VIT B12 DEFICIENCY
The other features are :
•Anorexia
•Dyspepsia
•Alternating constipation and diarrhoea
•Mild hepatosplenomegaly.

10. CLINICAL MANIFESTATIONS OF VIT B12 DEFICIENCY
The other features are :
•Purpura due to thrombocytopenia and
widespread melanin pigmentation are less
frequently observed.
•There may be infertility in young females.
•Other systemic features of anaemia may be
present.

11. CLINICAL MANIFESTATIONS OF FOLIC ACID
DEFICIENCY
•Folic acid deficiency manifests within a period of
few weeks to months.
•Glossitis is less common than in vitamin B12
deficiency.

12. CLINICAL MANIFESTATIONS OF FOLIC ACID
DEFICIENCY
•Neurological features are very rare. Only
depression, irritability, poor judgement,
forgetfulness and sleep deprivation have been
seen in some patients.
•Anorexia and occasional diarrhoea may be
present.

13. INVESTIGATIONS VIT B12 DEFICIENCY
Blood
•Haemoglobin levels range from 3-9 g/dl.
•Mean corpuscular volume (MCV) is over 110 fl
(normal 80-95).
•Mean corpuscular haemoglobin (MCH) and mean
corpuscular haemoglobin concentration (MCHC) are
usually normal.

14. INVESTIGATIONS VIT B12 DEFICIENCY
Blood
•Reticulocyte count is low in relation to degree of anemia.
•There is moderate leucopenia and thrombocytopenia.
•Peripheral smear shows oval macrocytes, macropolycytes, a
few myelocytes and occasional normoblasts .
• In a severely anaemic patient, megaloblasts may be seen in
the peripheral smear.

15. INVESTIGATIONS VIT B12 DEFICIENCY
Bone marrow
•The cell trails of bone marrow smears are
hypercellular with frequent mitoses and
increased myeloid: erythroid ratio.
•The characteristic features are: presence of
megaloblasts, giant bands and giant
metamyelocytes.

16. INVESTIGATIONS VIT B12 DEFICIENCY
•Bone marrow
•Megakaryocytes are decreased with basophilic
agranular cytoplasm and hypersegmented
nucleus.
•Bone marrow iron store is increased and
chromosome analysis of bone marrow cells and
PHA-stimulated cultures shows multiple
abnormalities.

17. INVESTIGATIONS FOLATE DEFICIENCY
Folate deficiency
•Blood and marrow findings are as in B12
deficiency.
•Serum folate is decreased below 3 µg/L and red
cell folate is much lower, below 160 µg/L.
•Vitamin B12 in serum is normal or borderline
normal.
•Serum LDH is increased.
•Serum bilirubin is increased.

18. INVESTIGATIONS FOLATE DEFICIENCY
Folate deficiency
•Abnormal deoxyuridine suppression test in bone
marrow culture is corrected by addition of N-5
methyl-THF or other folate supplement.
•Increased excretion of formimmunoglutamate (FIGLU)
in urine.
•Excess excretion of aminoimidazole carboxamide
(AICAR) in urine.
•Jejunal biopsy reveals pathological lesions in the small
intestine.

19. TREATMENT OF B12 DEFICIENCY
General management :
•This is similar to other cases of anaemia.
• For severe anaemia (Hb < 4 g/dl), packed red cell
transfusion is given slowly (15-30 drops/minute) along
with a diuretic (furosemide 40-80 mg).
•Before transfusion it is necessary to collect samples
for B12 and folic acid estimation.
•A bone marrow aspiration should also be performed
before transfusion.

20. TREATMENT OF B12 DEFICIENCY
Specific therapy :
• Hydroxycobalamin is given in doses of 1000 µg by
deep subcutaneous/intramuscular injection twice in
the first week and thereafter once a week for 6
weeks.
•Within 48 h after the first injection the bone marrow
becomes normoblastic.

21. TREATMENT OF B12 DEFICIENCY
Specific therapy :
•Within 2-3 days, reticulocyte count rises, reaching a peak
between the fifth and tenth days and falls gradually to
normal level on about the twentieth day.
•The leucocyte and platelet counts become normal in 7-10
days. Giant metamyelocytes persist up to 12 days in the
bone marrow but macropolycytes disappear in 2 weeks.

22. TREATMENT OF FOLATE DEFICIENCY
General management :
•The treatment of anemia is the same as that for
vitamin B12 deficiency.

23. TREATMENT OF FOLATE DEFICIENCY
Specific therapy :
•Oral folic acid (5-15 mg/day) should be given.
•It is given prophylactically (350 µg/day) to all pregnant
women, premature babies, patients receiving dialysis, and
in severe and chronic haemolytic states.
•Folic acid should not be given alone in megaloblastic
anaemia until vitamin B12 deficiency has been excluded,
since folate administration may precipitate neurological
changes by aggravating methionine deficiency in the brain.

24. TREATMENT OF FOLATE DEFICIENCY
Specific therapy :
•To patients receiving folic acid antagonists such as
methotrexate, folinic acid is given daily orally (15 mg) or
parenterally (3 mg/ml). Folinic acid mouth washes are
employed to obviate oral side-effects of folate antagonists.
Oral folic acid supplements can be used equally effectively.
•Megaloblastic anaemia due to other cytotoxic drugs which
inhibit DNA synthesis is not cured by vitamin B12 or folic acid
therapy.

25. TREATMENT OF FOLATE DEFICIENCY
Specific therapy :
•Patients treated with folic acid respond rapidly with a sense
of well being; reticulocytosis occurs in 5-7 days, and there is
total correction of haematologic abnormalities within two
months.
•In severely anaemic patients in whom there is no clear-cut
indication as to which deficiency is present, it is better to
give both vitamin B12 and folic acid. Moreover, co-existing
infection, if any, should be treated.