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ANEMIAS
Dr.Dejen G.
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• Anemia characterized by megaloblastic
erythropoeisis in the BM
– Hypercellualr marrow with megaloblasts but
ineffective erythropoesis
– No problem with hemoglobin synthesis
– But problem in nuclear maturation
– Most commonly due to Vit B12 and Folate deficiency
• NB. There are other causes of macrocytic anemia
but doesnot qualify as megaloblastic because of
absence of megaloblastic erythropoeisis
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VITAMIN B12 AND FOLIC ACID-PHYSIOLOGIC
CONSIDERATIONS
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• Folate acts as a coenzyme for many reactions in the
body
• Cobalamine serves as a cofactor for only two known
reactions
• For folate to function cobalamine is necessary
– Therefore all manifestations of folate deficiency can
result from VB12 deficiency
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an intermediate of the citric acid
Important for DNA synthesis, nervous
cycle, porphyrin synthesis
tissue and fat metabolism in the liver
(Heme synthesis)
MEGALOBLASTIC ANEMIAS
Causes of Vit.B12 deficiency
1. Malabsorption
a) Inadequate production of intrinsic factor:
pernicious anemia
gastrectomy, partial or total
b) Inadequate releasing vit. B12 from food (partial gastrectomy,
abnormality of stomach function, chronic pancreatic insufficiency)
c) Terminal ileum disease (sprue, celiac disease, ilea resection, Crohn
disease)
d) Competition for intestinal B12 :
• bacterial overgrowth:
– jejunal diverticula, intestinal stasis and
– obstruction due to strictures, blind-loop syndrome
• Fish tapeworm
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MEGALOBLASTIC ANEMIAS
Causes of Vit.B12 deficiency(2)
2. Inadequate intake
- vegetarians
3. Inadequate utilisation
Drugs: PAS, Neomycin, Colchicin, Nitrous oxide
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Absorption and
transport of vitamin
B12
MEGALOBLASTIC ANEMIAS- Causes of Folic acid deficiency
1. Inadequate intake
- diet lacking fresh, slightly cook food; chronic alcoholism, total parenteral nutrition,
2. Malabsorption
- small bowel disease (sprue, celiac disease,)
- alcoholism
3. Increased requirements:
- pregnancy and lactation
- infancy
- chronic hemolysis
- malignancy
- hemodialysis
4. Defective utilisation
Drugs:
– folate antagonists(methotrexate, trimethoprim, triamteren),
– purine analogs (azathioprine),
– primidine analogs (zidovudine),
– RNA reductase inhibitor (hydroxyurea),
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– miscellaneous (phenytoin, N2)
MEGALOBLASTIC ANEMIAS
clinical features
1. Symptoms of anemia and later pancytopenia, jaundice
2. Symptoms associated with vit. B12 or Folic acid deficiency
– Neurologic manifestations (exclusivly in Vit. B12 deficiency)
- megaloblastic madness or psychosis,
- subacute, combined degeneration of the spinal cord
( proprioceptive and vibratory sensation, spinal ataxia)
– Gastrointestinal compraints (vit.B 12 and folic acid deficiency)
- loss of appetite
- glosstis (red, sore, smooth tongue)
- diarrhea or constipation
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NERVOUS SYSTEM EFFECTS OF Vit B 12
deficiency
• Peripheral neuropathy
• Dementia
• Psychosis
• Subacute combined degeneration of the SC
– Posterior and lateral columns
• Weakness, ataxia, loss of vibration and position sense
• NB. Exact mechanism for the mechanism not known
but demyelination is the feature
• These manifestations are not observed in folate
defiecncy
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MEGALOBLASTIC ANEMIAS
Diagnosis(1)
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Macro-ovalocyte in megaloblastic anemia
MEGALOBLASTIC ANEMIAS
Diagnosis
3. Laboratory features
• Indirect hyperbilirubinemia
• elevation of lactate dehrogenase (LDH)
• serum iron concentration- normal or increased
4. Bone marrow smear
• Hypercellular
• increased erythroid /myeloid ratio
• erythroid cell changes (megaloblasts, RBC precursor a abnormally large
with nuclear- cytoplasmic asynchrony)
• myeloid cell changes (giant bands and metamyelocytes ,
hypertsegmentation)
• megakariocytes are decreased and show abnormal morphology
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MEGALOBLASTIC ANEMIAS
Diagnosis
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VIT B12 DEFICIENCY ANEMIA
DIAGNOSIS
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PERNICIOUS ANEMIA
DIAGNOSIS
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FOLIC ACID DEFICIENCY ANEMIA
DIAGNOSIS
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MEGALOBLASTIC ANEMIAS TREATMENT
PERNICIOUS ANEMIA
1. Vitamin B12 administration intramuscular in dose 1000 (100) μg per
day for a week , then 100 μg 2x per week for 2 weeks, 1 x per
week 100μg for month
3. 100 ug vit.B12 i.m. every month, regimen that must be mainted for
the rest on the patients life.
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MEGALOBLASTIC ANEMIAS TREATMENT(2)
FOLIC ACID DEFICIENCY ANEMIA
1. Oral administration of Folate 5 mg per day, for
3 months, and maintance therapy if it’s necessary.
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• NB. Treatment of megaloblastic anemia secondary
to VitB12 deficiency can be corrected by treatment
with folate but for un unknown reason the
neurologic manifestations can get excacerbated
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