MACROCYTIC ANAEMIA: ETIO-PATHOGENESIS
&
LAB DIAGNOSIS OF MACROCYTIC ANAEMIA
Dr. Tasnim Rahman
Associate Professor
Dept. of Pathology
Gazi Medical College, Khulna
MACROCYTIC ANAEMIA
MACROCYTIC ANAEMIA :
Macrocytic anaemia is defined as an anaemia, in which the red blood cells
are abnormally large (MCV of RBC is increased, >96 fl and the size of RBC
is greater than 8µm).
Normal MCV of RBC: 76-96fl
Normal diameter of RBC: 6-8µm (7.5µm)
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CLASSIFICATION OF MACROCYTIC ANAEMIA
MACROCYTIC ANAEMIA
Normoblastic Megaloblastic
macrocytic macrocytic
anaemia anaemia
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MACROCYTIC ANAEMIA
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MACROCYTIC ANAEMIA
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Morphological appearances of megaloblasts:
•
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Cell are larger compared to normoblast.
Nuclear size and amount of cytoplasm are increased in
megaloblasts.
• The nuclear chromatin of megaloblasts is sieve-like or stippled.
Chromatin clumping is less marked as cell matures.
• Howell – Jolly bodies are common.
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Morphological appearances of megaloblasts:
•
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The nuclear maturation ( progressive condensation of nuclear
chromatin ) falls behind cytoplasmic maturation. This is known as
nuclear–cytoplasmic asynchrony.
• The maturation of the nucleus lags behind that of cytoplasm.
• Mitotic activity is increased.
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Megaloblastic Anaemia
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Megaloblastic anaemias are a group of disorder characterized
by a macrocytic blood picture and megaloblastic erythropoiesis
due to deficiency of vitamin B12 and folic acid.
The macrocyte in this condition is usually “oval” - Hence
they are also called as MACRO OVALOCYTE.
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Pathogenesis of megalblastic anemia :
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B12 deficiency prevents conversion of methyl THF to THF.
Cell deprived of THF → decrease tetrahydrofolate polyglutamate coenzyme→
defective synthesis of DNA→ defect in nuclear maturation → Megaloblast .
Folate deficiency inhibits thymidylate synthesis→ decrease synthesis of Dtmp
(deoxythymidine monophosphate ) → Defective synthesis of DNA.
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CAUSES OF MEGALOBLASTIC
ANAEMIA
1. Vitamin B12 deficiency
2. Folate deficiency
3. Abnormalities of vitamin B12 or folate metabolism
4. Other defects of DNA synthesis
(e.g. congenital and acquired enzyme defieciency)
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Causes of vitamin b12 deficiency
1. Inadequate intake
2. Impaired absorption
a. Gastric causes:
• Pernicious anaemia
• Total or partial gastrectomy
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Causes of vitamin b12 deficiency
2. Impaired absorption
b. Intestinal cause
• Coeliac disease
• Tropical sprue
• Ileal resection and Crohn’s disease
• Fish tape worm infestation ( Diphyllobothrium
latum)
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Vitamin b12 deficiency :
There are three cardinal clinical features of vitamin B12
deficiency of whatever causes:
I. Macrocytic megaloblastic anaemia
II. Glossitis
III. Peripheral neuropathy and subacute combined
degeneration of spinal cord
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CAUSES OF FOLATE
DEFICIENCY
1. Inadequate intake
2. Impaired absorption
Coeliac disease
Tropical sprue
3. Increased demand
Pregnancy and lactation, puerperium
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Causes of normoblastic
Normoblastic macrocytic
macrocytic anaemia:
anaemia: Haemolytic anaemia
It is a disorder Post haemorrhagic anaemia
Alcoholism
characterized by a Liver disease
Aplastic anaemia
macrocytic blood picture but
Hypothyroidism
normoblastic erythropoiesis. Pregnancy
Smoking
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Pernicious anaemia
It may be defined as a chronic disorder of
middle and old age characterized by failure of
secretion of intrinsic factor due to gastric
atrophy.
Etiopathogenesis of Pernicious anaemia
Pathophysiology:
1. Autoantibody to gastric parietal cells
2. Autoantibody to IF
Two types:
– Blocking antibody: It blocks attachment of B12 to IF
– Binding antibody: It blocks B12-IF complex binding
to ileal receptor
Etiopathogenesis of Pernicious anaemia
Etiopathogenesis of Pernicious anaemia
Gastric atrophy
(Autoimmune)
Reduced intrinsic
factor secretion
Gastric juice
intrinsic factor
antibody
Failure of absorption
of dietary vitamin B
12
Deficiency of vitamin
B 12
Peripheral neuropathy and
Megaloblastic subacute combined
macrocytic anaemia Glossitis degeneration of spinal cord
Vit B 12 deficiency : Pernicious Anemia
CLINICAL FEATURES MACROCYTIC (MEGALOBLSTIC)
ANAEMIA :
Insidious onset of symptoms and signs of anaemia
Mild jaundice- lemon yellow tint
Glossitis : beefy –red tongue
Angular stomatitis
Peripheral neuropathy and subacute combined degeneration of the spinal cord
Neural tube defect-anencephaly, spina bifida
Loss of weight
Melanin pigmentation
Purpura
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CLINICAL FEATURES
Fig: Megaloblastic anaemia: a) Pallor and mild icterus b) Glossitis-the tongue is beefy red
and painful.
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LABORATORY DIAGNOSIS
1. Routine hematological examination:
Hb% - Reduced.
MCV - Increased (>96 fl and often as high as 120-140 fl in severe cases).
MCV above 125 fl are almost always associated with Vitamin B 12 or
folate deficiency and frankly megaloblastic bone marrow.
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LABORATORY DIAGNOSIS
2. Peripheral Blood Film:
RBC : Anisopoikilocytosis. Macrocytic (Macrocytes are oval in shape
in megaloblatic anemia) red blood cells, hence they are also called
as MACRO OVALOCYTES. Cell containing Howell jolly bodies,
basophilic stippling are often seen in megaloblastic anaemia. In
normoblastic macrocytic anaemia the macrocytes are round in
shape.
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LABORATORY DIAGNOSIS
2. Peripheral Blood Film:
▸ WBC : Leucopenia (neutropenia) with hypersegmented neutrophil. When
more than five percent of neutrophils have five lobes or the film shows at
least one one six-lobed cell. Hypersegmentation is an early sign of vitamin B
12 or folate deficiency and useful clue for diagnosis.
▸ Platelet : Mild thrombocytopenia may be present.
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LABORATORY DIAGNOSIS
Howel
jolly body
Hypersegment
ed neutrophils
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LABORATORY DIAGNOSIS
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LABORATORY DIAGNOSIS
Basophilic stippling
Fig: Megaloblastic anemia
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LABORATORY DIAGNOSIS
3. BONE MARROW STUDY:
▸ Cellularity : Hypercellular.
▸ M/E ratio : Decreased.
▸ Erythropoiesis : Hyperactive and megaloblastic change. There is
failure of nuclear maturation maintaining an open, fine, lacy
primitive chromatin pattern but normal hemoglobinization. Nuclear
maturation lags behind cytoplasmic maturation.
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LABORATORY DIAGNOSIS
3. BONE MARROW STUDY:
▸ Granulopoiesis : Active and large atypical granulocytes
at any stage usually metamyelocyte (Giant stab form).
▸ Megakaryopoiesis : Normal or slightly increased.
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LABORATORY DIAGNOSIS
4. Biochemical test:
▸ Serum B 12 assay
▸ Serum folate assay
▸ Red cell folate assay
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LABORATORY DIAGNOSIS
The confirmatory test of Bone marrow
megaloblastic anemia is
examination
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THANK YOU
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