ANEMIA AND ITS

PRACTICAL ASPECTS
ANEMIA AND ITS PRACTICAL
ASPECTS

PRESENTED BY
21. Himanjyoti Nath
22.Himraj Saharia
23.Hrishita Deka
PRESENTED BY- 24.Hritick Shyam Saikia
25.Jagmita Bhuyan
ROLL NO.- 21-26
26. Jahid Jeherul Islam
ANEMIA
 Defination :
Anemia is defined as reduced haemoglobin
concentration in blood below the lower limit of the
normal range for the age and sex of the individual.

REFERNCE RANGE FOR

MALE:
CLASSIFICATION OF ANEMIA

Widely accepted classification are based on two criteria:

 Pathophysiologic Classification
 Morphologic Classification
PATHOLOGIC CLASSIFICATION

1. Anemia due to blood loss

2. Anemia due to impaired red cell formation
3. Anemia due to increased red cell destruction
(Haemolytic Anemias)
MORPHOLOGIC
CLASSIFICATION :
MICROCYTIC ANEMIA

• Microcytic anemia is defined as the presence of small,

often hypochromic, red blood cell in a peripheral blood
smear and is usually characterized by a low mean
corpuscular volume{MCV}.
Types of Anemia Microcytic hypochromic
Size of RBC Smaller than normal
Central palor More than 1/3
Mean corpuscular volume Reduced {less than 80 fl}
Mean corpuscular haemoglobin conc. Reduced {less than 30 g/dl}
Examples Iron deficiency Anemia,
thalassemia
TYPES OF MICROCYTIC ANEMIA :

1. Iron deficiency Anemia

2. Thalassemia
3. Anemia of chronic disease
4. Sideroblastic Anemia
  IRON DEFICIENCY ANEMIA
• Deficiency of iron is the most common nutritional disorder in
the world and result in clinical signs and symptoms that are
mostly related to inadequate haemoglobin synthesis.
• The underlined iron deficiency differ somewhat in various
population groups and can be best considered in the context to
normal iron metabolism.
• Stages of iron deficiency anemia in sequence :

Absence of iron stores

decreased serum ferritin

decreased serum iron

increased TIBC

decreased iron saturation

microcytic hypochromic anemia

 CAUSES OF IRON DEFICIENCY
ANEMIA
• Iron deficiency anemia develops when the supply of iron is
inadequate for the requirement of Hb synthesis.
• The development of iron deficiency depends upon the
following factors –
1. Increased blood loss
2. Increased requirements
3. Inadequate dietary intake
4. Decreased intestinal absorption
 CLINICAL FEATURES
• As already mentioned, IDA is much more common in-
 women in between the age of 20-45 years
At period of active growth of infancy
Childhood and adolescence
More frequent in premature infants
  LAB FINDINGS
Peripheral blood:-
 Hemoglobin and haematocrit {PCV} decreased
 MCV < 80 fL {Normal 82-100 fL }
 MCH < 25 pg {Normal 27-32pg}
 MCHC < 27 g/dL {Normal 31-36 g/dL}
 RDW increased .It is the earliest sign of iron deficiency anemia.
Peripheral Smear :-
RBCs :- Microcytic and hypochromic. Severe anemia shows RING
cells.
Moderate Anisocytosis and Poikilocytosis with PENCIL cells.
WBCs: Normal
Platelets: Normal
Reticulocyte count: Low for the degree of anemia
Bone Marrow:
 Cellutarity: moderately hypercellular
Erythropoiesis: hyperplasia and micronormoblastic maturation
Megakaryopoiesis: Normal
SERUM IRON PROFILE
LAB FINDINGS IN IDA
PHYSICAL FINDINGS

• Decreased tissue enzymes causes characteristics

epithelial changes of IDA
Chronic atrophic gastritis
Koilonychia {spoon nails}
TREATMENT
• PRINCIPLES OF TREATMENT
• The management of IDA consists of two essential
priciples-
1) Correction of disorder
2) Correction of the disorder- Lack of iron is corrected
with iron therapy as under:
• 1)ORAL THERAPY-By administration of oral salts such as
ferrous sulphate , ferrous fumarate, ferrous glucanate and
polysaccharide iron
• 2) PARENTERAL THERAPY-Indicated by the following
types-
a)Intolerance of oral iron therapy
b)In GIT disorder such as malabsoption
c)Post operative cases
A common preparation for parenteral iron therapy is
IRON DEXTRAN which may be given as single IM injection
, or as IV infusion after dilution with DEXTRAN or saline.
APLASTIC ANEMIA

Defination- Chronic Primary haemopoietic stem cell

disorder .
• Characterised by
Pancytopenia {Anemia, neutropenia and
thrombocytopenia}
MACROCYTIC HYPOCHROMIC ANEMIA:

• Characterised by MCV> 98 fL
• RBC precursors have defective division leading to
macrocytosis.
• Associated with: 1. Liver disorders
2. Megaloblastic anemia
3. Chemotherapy drug use
4. Hypothyroidism
MEGALOBLASTIC ANEMIA:

• Defined as: Impairment of DNA synthesis that leads to

ineffective hematopoiesis and distinctive morphologic
changes, including abnormally large erythoid precursors
and red cells.
• Presence of megaloblasts in bone marrow.
CAUSES:
ANEMIA OF VIT B12 AND FOLATE
DEFICIENCY:

• Megaloblastic anemia caused by abnormal DNA

synthesis and nuclear maturation
• Vit B12 or Cobalamin is an
important dietary
requirement, produced
mainly by microbes.
Vegetarian diet contains
little of it.
• Absorption require:
Intrinsic factor.
• For Folic acid, humans are
entirely dependent on the
dietary source.
• During intestinal absorption,
they are modified into 5
methyltetrahydrofolate , the
normal transport form of
folic acid.
PATHOGENESIS OF MEGALOBLASTIC
CHANGE:

• Impaired DNA synthesis: Delayed maturation of nucleus

leading to nuclear-cytoplasmic asynchrony.
• Results in abnormally large nucleated erythroid precursors.
• Cytoplasm matures normally
• It affects all rapidly dividing cells.
• Ineffective erythropoiesis.
MEGALOBLAST:

• Large abnormal counterpart of normal normoblasts

• Shows asynchrony of nucleus and cytoplasm.
• Normal hemoglobinization.
• Ineffective erythropoiesis
• Giant metamyelocytes and band forms
• Megakaryopoiesis
 LABORATORY FINDINGS:

• Reduced HB and PCV In peripheral smear:

• Red cell indices: • RBCs: Macro-ovalocytes

(diagnostic), lack central
Increased MCV, MCH but
pallor, anisopoikilocytosis,
normal MCHC dyserythropoiesis.
• Reticulocyte count: • WBCs: Leukopenia,
Normal or low hypersegmented neutrophils.
• Platelet: Decrease in count.
Dimorphic anemia: Combined VitB12/folate and iron deficiency.
BIOCHEMICAL TESTS:

Common: For Vit B12:

• Serum bilirubin
• Serum methylmalonic acid
• Serum homocysteine
• Serum iron and ferritin • Urinary excretion of
• Plasma LDH methylmalonic acid
All characterised by an increase. • Schilling test
For folate:
• There is decrease in serum VitB12 and
folate. • FIGLU in urine shows
• Deoxyuridine suppression test. increased excretion.
PERNICIOUS ANEMIA:

• Autoimmune gastritis that impairs the production of

intrinsic factor.
• Histologically- chronic atrophis gastritis marked by loss
of parietal cells, infiltration by lymphocytes and plasma
cells.
• Autoantibodies: Type 1, 2 and 3
CLINICAL FEATURES:

• Fatigue and pallor (icterus also seen)

• Hyper pigmentation
• Atrophic glossitis
• Atrophic gastritis, achlorhydria
• VitB12 deficiency: Also shows neurological manifestations:
peripheral neuropathy and sub acute combined degeneration
(demyelination in the dorsal and lateral tracts)
APLASTIC ANEMIA

Defination- Chronic Primary haemopoietic stem cell

disorder .
• Characterised by
Pancytopenia {Anemia, neutropenia and
thrombocytopenia}
CAUSES

1) Acquired -
a)Idiopathic- Acquired defect in stem cell
Immune medated
b)Chemical agents- Cytotoxic drugs
Inorganic arsenicals
c) Idiosyncratic- Chloramphenicol
Gold salts
• Viral infections:Hepatitis Virus, cytomegalo Virus
• 2) Inherited- Fanconi anemia
Telomerase defects
CLINICAL FEATURES

• Any age of both sexes

• Insidious
• Progressive weakness, palor and Dyspnea
• Frequent infections due to neutropenia
LAB FINDINGS

• Peripharal blood-
Hb-decreased
PCV-decreased
Reticulocyte decreased
• Peripharal smear
RBC- Normocytic normochromic
WBC –decreased
Platelets- decreased
DIAGNOSIS

• Diagnosis is made with peripheral blood and bone

marrow Biopsy findings.
WHAT IS HAEMOLYTIC ANAEMIA?
• HEMOLYSIS can occur in two ways
1. INTRAVASCULAR 2.EXTRAVASCULAR
• Its Classification:
 HEREDITARY
SPHEROCYTOSIS
SEQUENCE OF HEMOLYSIS:

CLINICAL FEATURES-
1. Pallor
2. Jaundice
3. Splenomegaly
4. Aplastic Crisis
5. Pigment Gallstones
LAB FINDINGS
In Peripheral blood:
1.Spherocytosis
2. Reticulocytosis
3. Absoluete Red cell
indices : MCV
MCHC
Bone marrow findings
1. Markedly
hypercellular
2. Erythroid hyperplasia
Biochemical findings
3. Serum bilirubin:
mildly raised.
4. Urine urobilinogen:
increased.
5. Serum haptoglobin:
decreased.
Osmotic Fragility Test
Osmotic fragility is increased and there is shift
of the curve to the right

TREATMENT
SPLENECTOMY
ROLE
OF
G6PD:
GLUCOSE-6-PHOSPHATE DEHYDROGENASE
DEFICIENCY
EVENTS:
1. RBCs exposed to oxidant stress
2. H2O2 accumulation
3. RBC MEMBRANE damaged which releases Hb
4. Hb oxidised to Heinz Bodies
5. Heinz bodies removed by macrophages
6. Bite cell formed

CLINICAL FEATURES
1.Pallor
2.Jaundice
3. No splenomegaly and No gallstones
LAB FINDINGS:
Peripheral Blood
Haemoglobin: decreased.
Reticulocyte count: increased.
Peripheral smear: –
RBCs:Moderate anisopoikilocytosis
with polychromatophilia, micro
spherocytes and bite cells .
– WBCs: Mild leucocytosis.
– Platelets: Normal.
SCREENING TEST:

1. METHAEMOGLOBIN
REDUCTION TEST

2. FLUORESCENCE SPOT TEST

CONFIRMATORY
TEST:
G6PD ASSAY
PAROXYSMAL NOCTURNAL
HEMOGLOBINURIA
• Only acquired INTRACORPUSCULAR DEFECT
• PATHOGENESIS:
DIAGNOSIS:
1.Complete blood count –
Decreased Hb levels
Decreased Hematocrit
2.Ham’s acidified serum test and sucrose hemolysis test
positive.
Ham’s acidified serum test and sucrose hemolysis test:
Patient’s RBCs undergo lysis when incubated with
acidified serum (Ham test) or sugar (sucrose hemolysis
test).
3.Flow cytometry
: Detects RBC deficient in GPI-linked proteins (CD55
and CD59) and is useful for diagnosis of PNH.
TREATMENT- ECULIZUMAB, Hematopoietic Stem
cell transplantation
IMMUNE HEMOLYTIC ANEMIA
• Group of disorders characterised by production of
antibodies to red cells leading to their destruction.

(0°C to 4°C)
WARM AIHA
Spherocytes (blue arrows) with loss of central pallor, and polychyromatic cells
(one shown with black arrow) in a patient with warm autoimmune hemolytic
anemia
COLD AIHA
Low power view of a peripheral smear from a patient with cold
agglutin disease shows typical appearance of red cell agglutination 
 THALASSAEMIA

• They are a diverse group of hereditary disorders in which

there is decreased synthesis of globin polypeptide chains.
• It is a quantitative abnormality of polypeptide globin
chain synthesis.
GENETICS

• Globin chains are of four types- alpha , beta, gamma,

delta
• In normal adults the distribution of Hb is
HbA = 95-98%
HbA2=1.5-3.5%
HbF=<1% {Above 6 months}
• Two alpha globin chain- 4HbA gene on short arm of
chromosome 16
• Two beta globin chain- 2HbB gene on chromosome 11
CLASSIFICATION

• ON THE BASIS OF DELETION OF GENE

1) Alpha thalassemia
2) Beta thalassemia
1)ALPHA THALASSEMIA

• Defective synthesis of alpha globin chain

• Depending upon no of genes detected alpha thalassemia is of 4 types-

1)Hb barts hydrops foetalis { 4 genes }
2)Hb H disease {3 genes }
3) Alpha thalassemia trait {2 genes}
4)Alpha thalassemia trait carrier {1 gene }
 Hb Barts Hydrops Foetalis
 Total suppression of alpha chain
synthesis
 Gamma globin chain tetramer
 Clinical features-
Severe tissue hypoxia
Fetal
 Lab diagnosis-
Severe anemia {Hb < 6 gm/dl}
 PBS
Anisopoikilocytosis
Polychromasia
Microcytosis
Hypochromia
Basophillic stippling
Erythroblast
Target cell
 Reticulocyte count is high
 Serum bilirubin high
 Hb electrophoresis shows 60-90%
Hb barts
HbH Disease
 Impaired Alpha chain synthesis
 Gamma chain tetramer
 Clinical features-
Well compensated haemolytic anemia
Splenomegaly
Cholilithiasis
 Lab diagnosis-
Moderate anemia { Hb < 9g/dl}
 PBS
Microcytosis
Hypochromia
Basophillic stippling
Erythroblast
Target cell
 Reticulocyte count is mild
 HbH inclusion as HEINZ bodies
 Hb electrophoresis shows 2-4 %
HbH
ALPHA THALASSEMIA TRAIT

• Asymptomatic
• Lab findings-RBC is microcytic hypochromic
• Hb level is normal or mildly reduced
• MCV , MCH , MCHC slightly reduced
2)BETA THALASSEMIA

• Decreased in Beta chain synthesis

• Mutations having effect on Beta globin chain
1) Translational defect
2) Transcriptional defect
3) mRNA splicing defect
TYPES

1) Beta Thalassemia major

2) Beta Thalassemia intermediate
3) Beta Thalassemia minor
 SICKLE CELL ANEMIA
• It is a disorder of haemoglobin characterized by
production of defective Hb called Sickle Hb(HbS).
• On low oxygen tension or de-oxygenation HbS
imparts sickle shape to RBC
Characteristics features
Autosomal recessive disorder.
In HbS, there is substitution of Glutamic acid by Valine in the
6th position of Beta-globin chain of haemoglobin.
In sickle cell anemia, the RBC become rigid and sticky and
get stucked in small vessels which can slow or block blood
flow and oxygen to different parts of the body.
HbS has shorter life span.
 TYPES

oHbAA (Normal adult haemoglobin)

oHbSS (sickle cell anemia)

oHbAS (sickle cell trait)

 CLINICAL FEATURES
1. PALLOR
2. JAUNDICE
3. SPLENOMEGALY
4. DELAYED GROWTH
5. VISION PROBLEMS
 CRISIS
Periodic episode of pain called crisis are major symptoms of
sickle cell anemia.
It can be classified into 4 types
1. Sickling crisis :-
 most common
 Blockage of micro-circulation by sickle red cell produce hypoxic
injury and infarction.
 Bone : manifest as the hand-foot syndrome, dactility of bones of the
hands or feet or both.
 Lung: acute chest syndrome
2. Haemolytic crisis :-
 Rare type and presence with marked increased in haemolysis.

3. Aplastic crisis :-
 Associated with parvovirus B19
 Reticulocytopenia.

4. Sequestration crisis :-
 Usually occur in children
 Sudden trapping of blood in spleen or liver caused rapid enlargement
of the organ and drop in hematocrit leading to Hypo-volemic shock.
LAB FINDINGS
Peripheral Blood Serum finding

Hemoglobin decrease Serum Bilirubin increase

Hematocrit decrease Serum Haptoglobin reduced

ESR reduced Urine urobilinogen incresed

Reticulocyte count increase Serum iron , Serum ferritin raised

 PERIPHERAL BLOOD SMEAR FINDING
RBC
 nomcytic , normochromic to mildly
hypochromic
Moderate degree of
anisopoikilocytosis.
Sickle cell and target cell present
WBC mildly increased
Platelets mildly increased
Target cell sickle cell
DIAGNOSIS/CONFIRMATORY TEST
  SOLUBILITY TEST
• This is performed by adding the anticoagulant blood to the reducing
reagents solution ( consisting of phosphate buffer, saponin and sodium
dithionate). RBC are hemolysed and if HbS present, it will be reduced
by dithionate. HbS forms tactoid and refract light. The solution
appears turbid whereas normal Hb gives a clear solution.
  HEMOGLOBIN
ELECTROPHORESIS
• HbS is a slow moving compared to HbA and HbF.
 SICKLE CELL TRAIT
• Heterozygous state for the hemoglobin S mutaion and shows
HbA and HbS.
Clinical features:-
a. Asymptomatic
b. Normal growth and development, lifespan and life expectancy.
 Lab findings:-
a. RBC :- normocytic, normochromic with very few target cell and
mild degree of anisopoikilocytosis.
b. WBC normal, Platelets normal.
Diagnostics Test:-
A. Sickling test :- Sickling test is positive .

B. Hb electrophoresis

C. High performance Liquid Chromatography

REFERANCE

• ROBBINS AND COTRAN Textbook of PATHOLOGIC

BASIC OF DISEASE
• HARSH MOHON TEXTBOOK OF PATHOLOGY
• RAMADAS NAYAK Textbook of Pathology
• Class Notes