DR.

SAILENDRA NAYAK
ASSISTANT PROFESSOR
MEDICINE
 Learning Objectives
At the end of this briefing, you should know
• Clinical presentation of anemia.
• Definition of anemia.
• Approach to diagnosis of anemia
• Classification of anemia
• Distinct features of each type of anemia.
 Clinical presentation of anemias
• Fatigue and weakness • Menorrhagia
• Headache • Anorexia
• Tinnitus • Flatulence
• Numbness and coldness • Nausea
• Pallor • Constipation
• Dyspnea and palpitations
• Angina pectoris
• Intermittent claudication
• Hemorrhages in the
fundus of eyes
Clinical presentation of anemias
 Definition of Anemia

• Anemia is defined as a reduction in the concentration

of circulating haemoglobin below the level that is
expected for healthy persons of same age and sex in
the same environment.

6
Blood parameters (Laboratory Normal Range)
 Blood parameters (Laboratory Normal Range)

•In full term infants, hemoglobin is 18.0 ± 4.0 g/dl

•Children - 12.5 ± 1.5 g/dl
•Children(6-12 years) - 13.5 ± 2.0 g/dl
Grading of Anaemia
 Classification of Anaemias
• Morphological Classification
• Etiological Classification
• Classification based on reticulocyte response.
Morphological Classification of Anemias
 Hematocrit

• It is the fraction of whole blood composed of

red blood cells.

• Rules of Three:
– RBC X 3 = Hemoglobin
– Hemoglobin X 3 = Hematocrit

Packed cell volume (PCV) or Haematocrit (Hct)

Men - 0.40 -0.54 l/l (40-54%)
Women - 0.36 -0.46 l/l (36-46 % in non-
pregnant women
37±6 % in pregnant
women)
 Mean Corpuscular Volume

• Dividing the total volume of red cells by the

number of red cells
• Index for average size of red cells
• Normal range - 92 ± 8 fl
 Mean Corpuscular Hemoglobin
• Average amount of haemoglobin in each red
cell.
• It is expressed in picograms or pg.
• Normal range - 30± 3 pg
 Mean Corpuscular Hemoglobin Concentration

• This represents the average concentration of

haemoglobin in a given volume of packed red
cells.

• Normal range – 33 ± 2 g/dl

• MCHC raised in hereditary spherocytosis.
• Decreased in hypochromic anaemia.
 Red cell distribution width
• Variation in red cell size
• Normal range - 12.8% ± 1.2%
• Low in B-thalassemia trait
• High in iron deficiency anaemia
• Normal in anaemia of chronic disease
 Morphologic Categories of Anemia

1 2
1 Microcytic/hypochromic
2 Macrocytic/Normochromic

N.B. The nucleus of a small

lymphocyte (shown by the arrow)
is used as a reference to a
normal red cell size
3
3 Normocytic/Normochromic 17
 Macrocytic anemia
• Low/normal reticulocyte
count, macrocytosis(oval
and round)
• Elevated MCV,MCHC
• Basophilic stippling
• Howell-jolly bodies
• Cabot rings
• Pancytopenia
• Hypersegmente
d neutrophils
• Bone marrow-
megaloblastic
maturation,sieve
like
chromatin,nucle
ar-
cytoplasmic
asynchrony,maturatio
n arrest
Normocytic Normochromic anemia
with effective erythropoiesis
Etiological Classification of Anaemias
Basic Approach to a diagnosis of anemia
Evaluation of microcytic hypochromic anaemia
Evaluation of macrocytic anaemia
Evaluation of normocytic anaemia
Evaluation of haemolytic anaemia
A simplified approach to diagnosis of haemolytic
anaemias
 Reticulocyte Count
(In the Diagnosis of Anemia)
• Reticulocytes are non-
nucleated RBCs that still
contain RNA.
• Visualized by staining with
supravital dyes, including
new methylene blue or
brilliant cresyl blue.
• Useful in determining
response and potential of
bone marrow.
• Normal range is 0.5-2.5%
of all erythrocytes.
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 Fe++ deficiency anemia
• Low hemoglobin and low packed cell volume
• Low MCV,MCH and MCHC
• Microcytosis & hypochromia are hallmarks
• RDW is increased
• Serum ferritin is less than 15 micro gram/dl
• Serum iron is low,TIBC is increased and transferrin saturation is less
than 10 percent
• Free erythrocyte protoporphyrin is increased.
• Increased soluble transferrin receptor in serum
• Bone marrow-micronormoblastic,absence of stainable iron in bone
marrow on Perls Prussian blue reaction
 Megaloblastic Anemia
Mild to severe anemia,
– Increased MCV & MCH, normal MCHC
– Low RBC, HGB, WBC and PLT counts (fragile cells) due
to ineffective hematopoiesis.
– Low reticulocyte count
– Macrocytic ovalocytes and teardrops;
– Marked anisocytosis and poikilocytosis
– Schistocytes/microcytes - due to RBC breakage
upon leaving the BM
– Erythroid hyperplasia - low M:E ratio (1:1)
– Iron stores increased. 31
 Megaloblastic anemia
Howell-Jolly body

Teardrop
Schistocyte

Blood NRBC Blood

Macrocytic Ovalocytes
Stippled RBC &
Cabot Ring

Giant Platelet
Pap bodies Hypersegmented Neutrophil >5
lobes
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 Test
•
s
Folate and B12 levels
• Schilling test may be useful to establish
etiology of B12 deficiency
– Assesses radioactive B12 absorption with and
without exogenous IF
• Other tests if pernicious anemia is
suspected
– Anti- parietal cell antibodies, anti-IF
antibodies
– Secondary causes of poor absorption should be
sought (gastritis, ileal problems, etc.)
 Anemia of chronic disease
• Normocytic anemia with ineffective erythropoiesis
(reduced reticulocyte count)
• Normochromic
• Results from
– Chronic inflammation (e.g. rheumatologic disease):
Cytokines released by inflammatory cells cause
macrophages to accumulate iron and not transfer it to
plasma or developing red cells (iron block anemia)
– Inflammation
– malignancy
• Bone marrow suppression (EPO is elevated)
 Anemia of chronic disease
• Decreased serum iron,decreased total iron
binding capacity and normal or raised ferritin
• Increased marrow storage iron
• ESR is high
 Normochromic, normocytic anemia with
effective erythropoiesis
INCREASED reticulocyte count

• Acute blood loss

– Very acutely, with hypovolemia,
may have normal blood counts,
will become anemic with
volume replenishment
• Hemolytic anemia
– Increased reticulocyte
production cannot keep pace
with loss of RBCs peripherally.

• Response to specific therapy

in
nutritional anemias
 Aplastic anemia
• Pancytopenia caused by bone marrow
failure…decreased production of all cell
lines and replacement of marrow with
fat.
• Inherited- Fanconis anaemia, Dyskeratosis
congenita
• Acquired - Idiopathic,drugs like
NSAIDs,chloramphenicol,benzene,parvo
virus,hepatitis and EB virus.
 Hemolytic anemia
• Abnormality intrinsic to red cells-
1. Hereditary spherocytosis
2. Thalassamia
3. Sickle cell anaemia
4. Glucose -6-phosphate dehydrogenase
deficiency

• Abnormality extrinsic to red cells-

1. Immune
2. Mechanical etc
Evaluation of haemolytic anaemia
 Hereditary spherocytosis
• Inherited defect in the red cell membrane
cytoskeleton (spectrin, ankyrin or band 3)
leading to the formation of spherocytic red
cells.

• Autosomal dominant

• Mild to moderate anaemia

• Intermittent jaundice

• Splenomegaly

• Pigment gall stones

• Peripheral smear-microspherocytes

• Screening test-osmotic fragility

 Thalassemia

• Decreased or absent globin

chains
• Alpha and beta
thalassemias
• Microcytic
hypochromic,target
cells,basophilic stippling
• Reticulocytosis
• Hb F elevated in
electrophoresis
 Sickle cell anaemia

• Presence of Hb S
• Point mutation in 6th place of beta
chain
• Substitution of valine for glutamic acid
• On deoxygenation,sickle cells are
formed
• Chronic hemolytic anaemia,vaso-
occlusive crisis
• Aplastic crisis
• Hemolytic crisis
• Infections
 Sickle cell anaemia
• Sickling test is positive.
• Solubility test is positive.
• Electrophoresis shows HbS.
• In sickle cell trait, electrophoresis shows 60
percent of Hb A and 40 percent Hb S
 Glucose-6-phosphate dehydrogenase
deficiency
• X linked disorder
• Reduced activity of G6PD
• Inability to remove H2O2
• Accumulated H2O2 leads to
oxidation of hemoglobin
with precipitation of globin
chains
• Heinz bodies
• Red cells with heinz bodies
destroyed in
spleen(extravascular
hemolysis)
 Glucose-6-phosphate dehydrogenase
deficiency

• Asymptomatic
• Neonatal jaundice
• Acute hemolytic anaemia
• Chronic hemolytic anaemia
• On peripheral smear-
polychromasia,fragmented red
cells,spherocytes,bite cells,half
ghost cells
• Biochemical-increased
bilirubin,hemoglobinemia and
hemoglobinuria
 Glucose-6-phosphate dehydrogenase
deficiency
• Screening tests-fluorescent spot
test,methemoglobin reduction test and dye
decolorisation test
 Immune hemolytic anaemia
• Warm antibody-persons over 50 years,mild
jaundice and splenomegaly,red cells coated
with IgG,spherocytes.Seen in autoimmune
disorders,lymphoma
• Cold antibody-acrocyanosis,IgM.Seen in
cold agglutinin disease, Paroxysmal cold
hemoglobinuria (PCH)
 Coomb’s test
• Detects presence of either antibody on RBC or
of antibody in serum
• Helpful in determining if a hemolytic anemia is
immune-mediated
 SUMMARY
• Microcytic hypochromic anaemia-iron
deficiency
• Macrocytic hyperchromic-megaloblastic
anaemia
• Normochromic normocytic-hemolytic
anaemia
• Pancytopenia-megaloblastic and aplastic
anemias