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Megaloblastic and Other Macrocytic Anaemia: Dr. Nilukshi Perera Consultant Haematologist
Megaloblastic and Other Macrocytic Anaemia: Dr. Nilukshi Perera Consultant Haematologist
macrocytic anaemia
Dr. Nilukshi Perera
Consultant Haematologist
Requirements for Red
Blood Cell Production
Proteins, required
Erythropoietin
Proteins, required for globin synthesis
Iron
Vitamin B12 and folic acid
Vitamin B6 , B1, B2
Vitamin C , E
Thyroid hormones, estrogens and androgens
Zinc Iron
Calculation of RBC Indices
Mean corpuscular volume (MCV)=
Average RBC volume.
MCV= HCT X 10/RBC
Normal= 76-96 fl
Mean corpuscular heamoglobin
(MCH)=
Average weight of Hb in RBC.
MCH= Hb X 10/RBC
Normal= 27-32 pg
Calculation of RBC indices …….
Mean corpuscular heamoglobin
concentration (MCHC)=
Concentration of Hb in 100ml of RBCs.
MCHC= Hb X 100/Hct
Normal= 32-36 g/dL
RED CELL DISTRIBUTION WIDTH
(RDW)
Degree of Red Cell size variability in a
blood sample
Coefficient of variation of the size of
the RBCs
Expressed as %
Derived from automated instruments.
Normal: 11-15 %
MACROCYTIC ANEMIAS
Macrocytic anemias are characterized by
large RBCs with a normal hemoglobin
content.
2. Folate deficiency
Where is the defect
in the red cell in
megaloblastic
anaemia??
In the membrane,
cytoplasm or the
haemoglobin ??
Megaloblastic anemias are associated with
defective DNA synthesis and therefore,
abnormal RBC maturation in the bone
marrow (a nuclear maturation defect).
Mucosal cell
B12 absorption
Vitamin B12 and IF bind to mucosal cells
in the ileum and B12 enters.
When B12 is released from the mucosal
cell, it binds to transport proteins in the
bloodstream (transcobalamine IIII).
Type II is the primary transport protein.
Therefore a congenital deficiency in
type II can lead to a megaloblastic
anemia.
B12 is transported to the bone marrow
for use or to the liver for storage.
So ,
Everything that walks, swims or flies
contains vitamin B12. Nothing that
grows out of the ground contains
vitamin B12.
Causes of B12 Deficiency:
1. Nutritional
Especially vegans
2. Malabsorption
Gastrectomy
Ileal resection or bypass
Ileal disease (TB, lymphoma, amyloid, post-radiation, Crohn’s)
Enteropathies (protein losing, chronic diarrhea, celiac ,sprue)
Fish tapeworm (Diphyllobothrium latum) infection
Bacterial overgrowth
3. Inherited
Trans-Cbl II or IF deficiency
CAUSES OF B12 DEFICIENCY
Folic Acid
Normal daily intake 200-250g
Main foods Liver, greens, yeast
Cooking Easily destroyed
Minimal daily 100-150g
requirement & body 10-12mg (4mths supply)
stores
Absorption site Duodenum and jejunum
mechanism
Converted to methyl THF
Usual therapeutic form Folic acid
Causes of Folic Acid
Deficiency
Nutritional -old age, poverty, diet etc
Malabsorption- tropical sprue, coeliac
disease, Crohn’s disease
Excess utilization
Physiological-pregnancy, lactation, prematurity
Pathological-haemolytic anaemia,
myelofibrosis, malignant disease, inflammatory
disease
Drugs-anticonvulsants
Mixed-liver disease, alcoholism, intensive care
Megaloblastic Anaemia:
Clinical
Insidious onset of symptoms and signs of anaemia
Lemon yellow jaundice
Glossitis, angular stomatitis
Purpura
Neuropathy-subacute combined degeneration of the cord
(neuropathy affecting the peripheral sensory nerves and
posterior and lateral columns)
Deficiency during pregnancy cause nural tube defect in
baby.
Glossitis
In addition:
Tear drop poikilocytosis
The absolute reticulocyte count is decreased because of
ineffective erythropoiesis.
Pancytopenia is common.
Some NRBC when anaemia is severe.
Lab findings...............
Reticulocytopenia
Increased LDH
Mild increase of unconjugated bilirubin
Low serum B12 , serum & red cell folate levels.
PERIPHERAL SMEAR OF MEGALOBLASTIC
ANEMIA
Oval Macrocytes
Hypersegmented neutrophil
Oval macrocytes
Hypersegmented
neutrophil
Bone marrow
Hypercellular
Dyserythropoiesis
Giant metamyelocytes
Normal Megaloblastic
erythropoiesis erythropoiesis
Megaloblastic marrow Megaloblastic
erythroblast
Giant
metamyelocyte
Megaloblastic Anemia – Bone
Marrow
Megaloblastic anaemia
The bone marrow will show
hypercellularity, yet there are decreased
numbers of all cell types in the
peripheral blood because ineffective
hematopoiesis is occurring and many
cells are dying prematurely in the bone
marrow.
Pernicious anaemia
B12 deficiency due to autoimmune gastric atrophy.
Result in loss of intrinsic factor production.
Incidence increase after 40yrs
Associated with other autoimmune problems
(vitiligo, myxoedema, Hashimoto’s disease, thyrotoxicosis,
Addison’s disease etc)
Associated with blue eyes, early greying and blood group A.
Female>Male
Increased risk of gastric cancer
Diagnose with Schilling Test by using radioactive Vit B12 & IF
antibody levels
Manage with life long parenteral Vit B12 therapy
Pernicious Anemia
(PA)
Early graying
of hair
Blue eyes
Pernicious Anemia
Vitiligo
PA