Features of megaloblastic and non megaloblastic anemia
1. Describe the etiology and distinguishing features of
megaloblastic and non-megaloblastic macrocytic
anaemia
2. Normal RBC
•6.7–7.7 μm in size, round
with smooth contours, and
stain deep pink at the
periphery and paler in the
center.
•Central pallor –
approx.1/3rd the diameter
of the red cell.
•Size of a normal red cell -
size of the nucleus of a small
lymphocyte.
•Normal red cells -
normocytic and
normochromic.
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4. Anemia
Anemia is a condition in which red blood cells or their
oxygen carrying capacity is insufficient to meet
physiological needs which vary by age, sex, altitude ,
smoking and pregnancy status.
11. Macrocytic Anemia
• Macrocytic anemia simply means
anemia with MCV > 100 fl
• These can be divided into
megaloblastic and non-
megaloblastic type
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Megaloblastic
anemia
B12 deficiency
• (Pernicious
anemiak
Folate deficiency
• (Dietary
insufficiency)
Non
Megaloblastic
anemia
Alcohol
Reticulocytosis
•(Haemolysis)
Liver disease
Hypothyroidism
Singh T. Atlas and text of hematology. Avichal Pub-lishing
Company, New Delhi. 2010;136.
13. Macrocytic
Anemia
PERIPHERAL SMEAR:
Macro ovalocytes in which central
pallor is reduced
Basophilic stippling
Howell Jolly bodies
Cabot rings
Neutrophil hyper segmentation
Pancytopenia
14. Macrocytic Anemia
o Red cells are larger than the nucleus
of the small lymphocyte (Size > 8.5
μm in diameter)
o >3% neutrophils showing 5 or more
lobes or > 1 neutrophil with 6 or more
lobes.
o Defect in the production of DNA
causes the maturation process to be
slower than normal which in turn
causes the nucleus to hypersegment.
o Seen in
1. Megaloblastic anemia
2. MDS
3. PATIENT ON CHEMOTHERAPY
To differentiate Megaloblastic anemia from non megaloblastic anemia: Neutrophil
hypersegmentation or Macro-ovalocytes
15. BASOPHILIC
STIPPLING
• Numerous small, purplish
inclusions, which result from
RNA and mitochondrial
remnants.
• Seen in
• Lead toxicity
• Thalassemias
• Hemoglobinopathies
• Macrocytic anemias
16. Cabot rings
• Cabot rings are delicate thread-like
inclusions, remnants of the nuclear
membranes, in the RBC
• variety of shapes and sizes.
• Purplish rings, figures-of-eight,
incomplete rings appearing in the
center or near the periphery of
erythrocytes.
• Seen in
• Pernicious anemia
• Lead poisoning
• Alcoholic jaundice
• Severe anemia
• Leukemia.
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17. Howell-Jolly bodies
• Small, well-defined, round, densely
stained inclusions; 1 μm in diameter,
eccentric in location that represent
DNA fragments which were once part
of the nucleus of immature red cells.
• Howell-Jolly bodies are seen in
• Postsplenectomy or hyposplenia
• Newborn
• Megaloblastic anemias
• Dyserythropoietic anemias
• Hereditary spherocytosis.
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19. Megaloblast
• Abnormal red cell precursor.
• Nuclear maturation lags
behind cytoplasmic
maturation.
• Chromatin is less condensed
than that of a normoblast.
(sieve like )
• Nucleus is irregular
• May contain Howell jolly
bodies.
20. Erythroid
Hyperplasia
• It is a condition of excessive
count of erythroid precursor
cells in the bone marrow.
• Usually a compensatory
condition
• Can result from
1.Increased erythropoietin
production
2.Increased peripheral
erythrocyte loss
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21. Giant
metamyelocyte
• Size: 10 to 15 μm
• N:C: 1:1
• Chromatin: Indented-
shaped nucleus resembling a
kidney structure, patches of
coarse chromatin in spots.
• Cytoplasm: Pale blue to
pinkish tan with moderate
specific granules.
• Differentiating
characteristics: Nuclear
indentation and condensed
chromatin with no nuclei.
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24. Megaloblastic Anemia
Metabolic function of vitamin B12 & folic acid
Homocysteine THF
Methyl B12
Methionine N-5-METHYL THF
N5, 10 methylene THF
dUMP dTMP
DNA
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Methylmalonyl
CoA
Succinyl CoA
B12
Singh T. Atlas and text of hematology. Avichal Pub-lishing Company, New Delhi. 2010;136.
28. Non-
Megaloblastic
Anemia
Macrocytic Anemia in which RBC precursors
appear normal without characteristic Nuclear
and Cytoplasmic findings of Megaloblastosis.
DNA synthesis is unimpaired
MCV is usually 100-110fl
Macrocytosis is usually mild
4/14/2024 Wintrobe MM. Wintrobe's clinical hematology. Lippincott Williams & Wilkins; 2008.
30. Non-
Megaloblastic
Anemia
1. Macrocytosis of Alcoholism:
Due to direct effect of alcohol on bone marrow
and antibodies against acetaldehyde modified
RBC protein
MCV elevation usually slight (100-110 fl)
Minimal or no anemia
Macrocytes round (not oval)
Neutrophil hypersegmentation absent
Folate stores normal
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31. Non-Megaloblastic
Anemia
2. Liver disease:
Thin macrocytes: increase surface area without
increase in volume due to excessive membrane
lipids, especially. cholesterol, but also
phospholipids.
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Spur cells
33. Diagnosis
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B12 Deficiency anemia
Peripheral blood smear
-Show large RBC’s (macro-ovalocyte)
-Hypersegmented Neutrophils
Bone Marrow Study
- Megaloblastic changes in RBC’s precursor at various stages of
differentiation .
Biochemical test
- Homocysteine Levels & Methylmalonic acid Levels are elevated
- Schilling test
Folic acid Deficiency anemia
No neurological symptoms occur as methylmalonic acid levels are
normal.
Homocysteine level are elevated
Methylmalonic acid levels are normal
34. Cases
Case 1
• 65 year old Male
• Caucasian
• C/O frequent fall
• Low Hb levels
35. Case 1
Frequent fall suggestive of neurological dysfunction
VIT B12 deficiency
Confirmed on P/S findings
Rule out low dietary intake
Pinpoint the cause of dec. absorption
• Anti intrinsic factor antibody for pernicious anemia
• Endoscopic/imaging studies for Chron’s disease
36. •50 year old , Female
•Hispasian individual
•History of chronic alcoholic consumption
•Mouth sores
•Low hb level
Case 2
37. Case 2
Based on history of alcohol use
Folate deficiency
Confirmation By P/S
Homocysteine levels
• Methyl Malonyc acid levels