HAEMATOLOGY

Iron def. Sideroblastic, Chronic disease, Megaloblastic anaemia

Dr. PRIYANKA SACHDEV , MD

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Dr. PRIYANKA SACHDEV

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Hematology is the study of the various
cells and components of the blood→

1. RBC
2. WBC
3. Platelets
Dr. PRIYANKA SACHDEV
•Circulating blood normally contains 3
main types of mature blood cells—

1. The red cells (erythrocytes)

2. The white cells (leucocytes)
3. The platelets (thrombocytes)
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 HAEMATOPOIESIS

•Haematopoiesis is production of formed

elements of the blood.

•Normally, it takes place in the bone

marrow.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
HAEMATOPOIETIC ORGANS

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
•Ratio of myeloid to erythroid (M:E ratio)
is 3 : 1

•Ratio of fat cells to erythroid cells is 4: 1

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 HSC

Lymphoid stem cells Myeloid (trilineage) stem cells

Prolymphocyte

Granulocyte-monocyte p. Erythroid p Megakaryocytes

T, B and NK cells Neutrophils RBC Platelet

Eosinophils
Basophils
Monocytes
Dr. PRIYANKA SACHDEV
 RBC
Dr. PRIYANKA SACHDEV
 ERYTHROPOIESIS
•Erythropoiesis is production of mature
erythrocytes of the peripheral blood
from HSC which takes place in the bone
marrow.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
• The following stages of development occur within the bone marrow
sequentially →

• 1) Pluripotent hematopoietic stem cell

• 2) Multipotent stem cell
• 3) Unipotent stem cell
• 4) Pronormoblast
• 5) Early normoblast / Basophilic erythroblast
• 6) Intermediate normoblast / Polychromatic erythroblast
• 7) Late normoblast / Orthochromatic erythroblast
• 8) Reticulocyte
Dr. PRIYANKA SACHDEV
ERYTHROID SERIES

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
ERYTHROID SERIES

Dr. PRIYANKA SACHDEV

During maturation following changes take place : -

• i) Reduction in cell size

• ii) Cytoplasm changes from bosophilic to acidophilic.
• iii) Nucleus disappears at reticulocyte stage because it is
extruded in late normoblast stage
• iv) Hemoglobin appears at intermediate normoblast stage
• v) Mitosis occurs upto the stage of intermediate normoblast and
mitosis is most active at this stage. Late normoblast is not
capable of mitotic division.

Dr. PRIYANKA SACHDEV

ERYTHROID SERIES

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Morphology of
RBC

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
•The hemoglobin of red cells is located
peripherally, leaving an area of central
pallor equal to approximately 30-35% of
diameter of the cells ( Central 1/3rd pallor)

•The lifespan of red cells is 120 + 30 days.

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 VARIATIONS IN SIZE
•RBC of normal size → Normocytic

•When red cell diameter is greater than 9 μm

they are referred as macrocytes

•When red cell diameter is less than 6 μm

they are referred as microcytes
Dr. PRIYANKA SACHDEV
 REMEMBER
•On smear size of RBC is compared with
small lymphocyte

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 VARIATIONS IN COLOUR

•RBC with normal hemoglobin content (color) (

Central 1/3rd pallor) → Normochromic

•When area of central pollar is greater than

50% of diameter, it is referred as hypochromic

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
•Variation is size of RBCs is know as
anisocytosis

•Variation in shape of RBCs is know as

poikilocytosis

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
ANAEMIA
 ANAEMIA

•Anemia is defined as a reduction of the total

circulating red cell mass below normal limits

•In practice, the measurement of red cell mass is

not easy, and anemia is usually diagnosed
based on a reduction in hemoglobin
concentration
Dr. PRIYANKA SACHDEV
•Anaemia is defined as reduced
haemoglobin concentration in blood
below the lower limit of the normal
range for the age and sex of the
individual.

Dr. PRIYANKA SACHDEV

•The lower extreme of the normal
haemoglobin is taken as →

➢13.0 g/dl for males

➢11.5 g/dl for females
➢15 g/dl for newborns
Dr. PRIYANKA SACHDEV
 CLASSIFICATION OF ANAEMIAS

1. MORHOLOGICAL CLASSIFICATION

2. PATHOPHYSIOLOGICAL CLASSIFICATION

Dr. PRIYANKA SACHDEV

MORHOLOGICAL CLASSIFICATION

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 MORPHOLOGIC CLASSIFICATION
1. Microcytic, hypochromic
• MCV, MCH, MCHC are all reduced e.g. in iron deficiency anaemia
and in certain non iron deficient anaemias (sideroblastic anaemia,
thalassaemia, anaemia of chronic disorders).

2. Normocytic, normochromic
• MCV, MCH, MCHC are all normal e.g. after acute blood loss,
haemolytic anaemias, bone marrow failure, anaemia of chronic
disorders.

3. Macrocytic, normochromic
• MCV is raised e.g. in megaloblastic anaemia due to deficiency of
vitamin B12 or folic acid.
Dr. PRIYANKA SACHDEV
 CLASSIFICATION OF ANAEMIAS

1. MORHOLOGICAL CLASSIFICATION

2. PATHOPHYSIOLOGICAL CLASSIFICATION

Dr. PRIYANKA SACHDEV

 PATHOPHYSIOLOGICAL/
ETIOLOGICAL CLASSIFICATION

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
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Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
IRON DEFICIENCY ANAEMIA

Dr. PRIYANKA SACHDEV

 OVERVIEW
•Introduction
•Normal iron metabolism
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment
Dr. PRIYANKA SACHDEV
 Introduction

•It is the most common cause of anemia

worldwide and in India

• Its prevalence is higher in the developing

countries.

Dr. PRIYANKA SACHDEV

 OVERVIEW
•Introduction
•Normal iron metabolism
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment
Dr. PRIYANKA SACHDEV
 Normal iron metabolism

A)Absorption
B)Transport and storage

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 A) Iron absorption
•Iron is absorbed from upper small intestine
mainly duodenum
• In diet iron occurs in two forms
1. Haeme iron (animal products)
2. Inorganic (non-haeme) iron (vegetables)

•Haem iron is better absorbed (20%)than

inorganic iron (1-2%) but the major fraction of
diet is inorganic iron.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Nonheme iron
•Nonheme iron is mostly in the Fe3+ (ferric)
state

•Must first be reduced to Fe2+ (ferrous) iron in

gastric acid

•Fe2+ iron is then transported across the apical

membrane by divalent metal transporter 1
(DMT1)
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Heme iron
•Heme iron is moved across the apical
membrane into the cytoplasm through
Heme transporters

•Here, it is metabolized to release Fe2+

iron, which enters a common pool with
nonheme Fe2+ iron.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Fe2+ iron is transported from the cytoplasm across the
basolateral enterocyte membrane by ferroportin

This process is coupled to the oxidation of Fe2+ iron to

Fe3+ iron, which is carried out by the iron oxidases
hephaestin and ceruloplasmin

Newly absorbed Fe3+ iron binds rapidly to the plasma

protein transferrin

Dr. PRIYANKA SACHDEV

 Newly absorbed Fe3+ iron binds rapidly to the plasma
protein transferrin

Transferrin delivers iron to red cell progenitors in the

marrow
Each molecule of transferrin can transport two molecules
of iron to the desired areas

Extra iron is stored in liver in the form of feritin

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Regulation of iron absorption
•Iron absorption is regulated by hepcidin

•Hepcidin is synthesized and released

from the liver in response to increases in
intrahepatic iron levels.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Hepcidin binds to ferroportin

Degrade it

Inhibits iron transfer from the enterocyte to plasma

Iron becomes trapped within duodenal cells

Iron is lost as these cells are sloughed.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
1. When the body is replete with iron → high hepcidin
levels → inhibit iron absorption into the blood

2. When body iron stores is low → hepcidin synthesis

falls → facilitates iron absorption into the blood

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 REMEMBER

•Iron is transported is blood in combination

with a glycoprotein transferrin.
•Iron is stored as ferritin or haemosiderin.

• Ferritin is a complex of iron and apoferritin

(iron + apoferritin = ferritin)
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 OVERVIEW
•Introduction
•Normal iron metabolism
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment
Dr. PRIYANKA SACHDEV
 ETIOLOGY

1. Increased blood loss

2. Increased requirement
3. Inadequate dietary intake
4. Decreased absorption

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 OVERVIEW
•Introduction
•Normal iron metabolism
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment
Dr. PRIYANKA SACHDEV
 PATHOGENESIS
•Iron deficiency anaemia develops when
the supply of iron is inadequate for the
requirement of haemoglobin synthesis.

Dr. PRIYANKA SACHDEV

• Initially, negative iron balance is covered by mobilisation from the
tissue stores so as to maintain haemoglobin synthesis.

• Progressive depletion of these reserves first lowers serum iron and

transferrin saturation levels without producing anemia

• In this early stage there is increased erythroid activity in the bone

marrow

• It is only after the tissue stores of iron are exhausted that the supply of
iron to the marrow becomes insufficient for haemoglobin formation
• Thus a state of iron deficiency anaemia develops.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Stages of anaemia- 3 stages:

•1. Storage iron depletion occurs during which

iron reserves are lost without compromise of the
iron supply for Erythropoiesis
•2. Iron deficient erythropoiesis during which the
erythroid iron supply is reduced without the
development of anaemia.
•3. Frank iron deficiency anaemia when the red
cells become microcytic and hypochromic
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 POLLS 1

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Dr. PRIYANKA SACHDEV
B

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D

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A

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B

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A

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 OVERVIEW
•Introduction
•Normal iron metabolism
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment
Dr. PRIYANKA SACHDEV
 CLINICAL FEATURES
1.ANAEMIA
• Weakness
• Fatigue,
• Dyspnoea on exertion
• Palpitations
• Pallor of the skin, mucous membranes
and sclerae.
• Older patients may develop angina and
congestive cardiac failure.
Dr. PRIYANKA SACHDEV
2. EPITHELIAL TISSUE CHANGES
• Nails (koilonychias or spoon-shaped nails)
• Tongue (atrophic glossitis),
• Mouth (angular stomatitis),
• Oesophagus causing dysphagia from development of
thin, membranous webs at the postcricoid area
(Plummer-Vinson syndrome)

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
2. EPITHELIAL TISSUE CHANGES
• Nails (koilonychias or spoon-shaped nails)
• Tongue (atrophic glossitis),
• Mouth (angular stomatitis),
• Oesophagus causing dysphagia from development of
thin, membranous webs at the postcricoid area
(Plummer-Vinson syndrome)

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
2. EPITHELIAL TISSUE CHANGES
• Nails (koilonychias or spoon-shaped nails)
• Tongue (atrophic glossitis),
• Mouth (angular stomatitis),
• Oesophagus causing dysphagia from development of
thin, membranous webs at the postcricoid area
(Plummer-Vinson syndrome)

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 OVERVIEW
•Introduction
•Normal iron metabolism
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment
Dr. PRIYANKA SACHDEV
 LABORATORY FINDINGS

1. BLOOD PICTURE AND RED CELL INDICES

2. BONE MARROW FINDINGS

3. BIOCHEMICAL FINDINGS
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
1. BLOOD PICTURE AND RED CELL
INDICES

i) Haemoglobin
•The essential feature is a fall in
haemoglobin concentration up to a
variable degree.

Dr. PRIYANKA SACHDEV

ii) Red cells
• The red cells in the blood film are hypochromic and microcytic
• Hypochromia generally precedes microcytosis.
• Hypochromia is due to poor filling of the red cells with
haemoglobin so that there is increased central pallor.
• there is anisocytosis and poikilocytosis
• Target cells, elliptical forms and polychromatic cells are often
present
• Ring / pessary cells (central pallor occupies whole cell and only
peripheral rim of hemoglobin is seen).
Dr. PRIYANKA SACHDEV
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Dr. PRIYANKA SACHDEV
•When iron deficiency is associated with
severe folate or vitamin B12 deficiency, a
dimorphic blood picture occurs with dual
population of red cells—

macrocytic as well as microcytic

hypochromic
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
iii) Reticulocyte count
• The reticulocyte count is normal but may be slightly low

iv) Indices
• Diminished MCV (below 50 fl),
• Diminished MCH (below 15 pg),
• Diminished MCHC (below 20 g/dl).

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
v) Leucocytes
• The total and differential white cell counts are usually
normal

vi) Platelets
• Platelet count is usually normal

Dr. PRIYANKA SACHDEV

 LABORATORY FINDINGS

1. BLOOD PICTURE AND RED CELL INDICES

2. BONE MARROW FINDINGS

3. BIOCHEMICAL FINDINGS
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 2. BONE MARROW FINDINGS

i) Marrow cellularity

• The marrow cellularity is increased due to erythroid

hyperplasia

• Myeloid-erythroid ratio decreased

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
ii) Erythropoiesis

• There is normoblastic erythropoiesis with predominance of

small normoblasts. (micronormoblast)

• The cytoplasmic maturation lags behind nuclear maturation

(the late normoblasts have pyknotic nucleus but persisting
polychromatic cytoplasm)

• (compared from megaloblastic anaemia in which the nuclear

maturation lags behind).
Dr. PRIYANKA SACHDEV
ERYTHROID SERIES

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
iii) Other cells → Myeloid, lymphoid and megakaryocytic cells
are normal in number and morphology.

iv) Marrow iron

• Iron staining (Prussian blue reaction) on bone marrow aspirate
smear shows deficient iron stores and absence of siderotic iron
granules

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 LABORATORY FINDINGS

1. BLOOD PICTURE AND RED CELL INDICES

2. BONE MARROW FINDINGS

3. BIOCHEMICAL FINDINGS
Dr. PRIYANKA SACHDEV
 3. BIOCHEMICAL FINDINGS

i) The serum iron level

•It is low
•Normal 40-140 μg/dl
•It is under 50 μg/dl.
•When serum iron falls below 15 μg/dl,
marrow iron stores are absent.
Dr. PRIYANKA SACHDEV
ii) Serum ferritin level

•Normal 30-250 ng/ml

•It is very low
•Indicating poor tissue iron stores.
Dr. PRIYANKA SACHDEV
•iii) Total iron binding capacity (TIBC)
and Transferrin saturation

• Total iron binding capacity (TIBC) is high

•Transferrin saturation to low below 15%.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
iv) Serum transferrin receptor protein

• This is normally present on developing erythroid cells

• It is raised in iron deficiency
• (normal level 4-9 μg/L as determined by immunoassay).

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 OVERVIEW
•Introduction
•Normal iron metabolism
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment
Dr. PRIYANKA SACHDEV
 Differential diagnosis of microcytic
hypochromic anemia

1. Iron deficiency anemia

2. Anemia of chronic disease
3. Thalassemia
4. Sideroblastic anemia
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
There are some indices which help to differentiate thalassemia minor from
iron deficiency anemia

Dr. PRIYANKA SACHDEV

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In iron deficiency anaemia, values of the following are
decreased EXCEPT

• a) M.C.V. (Mean corpuscular Volume).

• b) serum iron
• c) mean Corpuscular Haemoglobin
• d) total iron binding capacity

Dr. PRIYANKA SACHDEV

D

Dr. PRIYANKA SACHDEV

The commonest cause of microcystic hypochromic
anaemia is

• a) thallassemia
• b) megaloblastic anaemia.
• c) iron deficiency anaemia
• d) sideroblastic anaemia

Dr. PRIYANKA SACHDEV

C

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
A

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Dr. PRIYANKA SACHDEV
D

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C

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B

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 OVERVIEW
•Introduction
•Normal iron metabolism
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment
Dr. PRIYANKA SACHDEV
 TREATMENT

2 essential principles:

1. Correction of disorder causing the

anemia
2. Correction of iron deficiency.
Dr. PRIYANKA SACHDEV
1. CORRECTION OF THE DISORDER

1.CORRECTION OF THE DISORDER

•Thorough check-up and investigations.

•Appropriate surgical, medical or
preventive measures are instituted to
correct the cause of blood loss.
Dr. PRIYANKA SACHDEV
 2. CORRECTION OF IRON
DEFICIENCY
1. Oral therapy
2. Parenteral therapy

Dr. PRIYANKA SACHDEV

 1. Oral therapy
•Oral iron salts such as

1. Ferrous sulfate
2. Ferrous fumarate
3. Ferrous gluconate

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
• Optimal absorption is obtained by giving iron fasting, but
if side-effects occur (e.g. nausea, abdominal discomfort,
diarrhoea). So given with food

• Oral iron therapy is continued long enough, both to

correct the anaemia and to replenish the body iron
stores.

• The response to oral iron therapy is observed by

reticulocytosis which begins to appear in 3-4 days with a
peak in about 10 days.

Dr. PRIYANKA SACHDEV

 2. CORRECTION OF IRON
DEFICIENCY
1. Oral therapy
2. Parenteral therapy

Dr. PRIYANKA SACHDEV

 2. Parenteral therapy
Indications→

•a) Intolerance to oral iron therapy

•b) In GIT disorders such as malabsorption
•c) Post-operative cases
•d) Cases requiring a rapid replenishment of iron
stores e.g. in women with severe anaemia a few
weeks before expected date of delivery.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
•Parenteral iron therapy is hazardous and
expensive when compared with oral
administration.

•The haematological response to parenteral

iron therapy is no faster than the
administration of adequate dose of oral iron
but the stores are replenished much faster.
Dr. PRIYANKA SACHDEV
•Common preparation is iron dextran which
may be given as a single intramuscular
injection, or as intravenous infusion after
dilution with dextrose or saline.

Dr. PRIYANKA SACHDEV

• Before giving the parenteral iron, total dose is calculated
by a simple formula→
By multiplying the grams of haemoglobin below normal
with 250 (250 mg of elemental iron is required for each
gram of deficit haemoglobin), plus an additional 500 mg is
added for building up iron stores.

(Grams of haemoglobin X 250) + 500 mg

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 RESPONSE TO THERAPY
1. The earliest response to iron therapy is
marked improvement in subjective
symptoms e.g. decrease in fatigue, lassitude
and other nonspecific symptoms.

2. The earliest hematological evidence of

improvement is increase in reticulocytes
Dr. PRIYANKA SACHDEV
 OVERVIEW
•Introduction
•Normal iron metabolism
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment
Dr. PRIYANKA SACHDEV
 POLLS 3

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Dr. PRIYANKA SACHDEV
B

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PATHOPHYSIOLOGICAL
CLASSIFICATION

Dr. PRIYANKA SACHDEV

SIDEROBLASTIC ANAEMIA

Dr. PRIYANKA SACHDEV

 OVERVIEW
•Introduction
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment Dr. PRIYANKA SACHDEV
 Introduction
•Sideroblastic anemia is a type of anemia in
which the body has adequate amount of iron
but is unable to corporate it into hemoglobin.

•Siderocytes and sideroblasts are erythrocytes

and normoblasts respectively which contain
cytoplasmic granules of iron
Dr. PRIYANKA SACHDEV
 Headings
•Introduction
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment Dr. PRIYANKA SACHDEV
 ETIOLOGY
•The basis defect is a failure to completely form
heme molecules, whose biosynthesis takes
place partly in the mitochondria.

•The iron enters into the mitochondria, but

cannot be utilized to synthesize heme.

•So iron, accumulates in mitochrondria giving a

ringed appearance Ringed sideroblast (seen by
peal’s stain)
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
HAEMOGLOBIN SYNTHESIS

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
SIDEROBLASTS

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 OVERVIEW
•Introduction
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment Dr. PRIYANKA SACHDEV
PATHOGENESIS

Dr. PRIYANKA SACHDEV

 TYPES OF SIDEROBLASTIC
ANAEMIAS
I. HEREDITARY SIDEROBLASTIC ANAEMIA

II. ACQUIRED SIDEROBLASTIC ANAEMIA

Dr. PRIYANKA SACHDEV

 I. HEREDITARY SIDEROBLASTIC
ANAEMIA

•A rare X-linked disorder associated with

defective enzyme activity of
aminolevulinic acid (ALA) synthetase
required for haem synthesis.

Dr. PRIYANKA SACHDEV

HAEMOGLOBIN SYNTHESIS

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
II. ACQUIRED SIDEROBLASTIC ANAEMIA

• i) Hematological : Mylofibrosis , myelodysplasia , acute leukemia,

lymphoma, myeloma, polycythemia vera.

• ii) Substances /drugs : Lead , INH , chloramphenicol, penicillamine,

alcohol , deficiency of pyridoxine.

• iii) Others : Collagen vascular diseases like SLE, porphyria, iron overload ,
RA, myxedema, hereditary (X-linked recessive).

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 OVERVIEW
•Introduction
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment Dr. PRIYANKA SACHDEV
 LABORATORY FINDINGS
1. BLOOD PICTURE AND RED CELL INDICES

2. BONE MARROW FINDINGS

3. BIOCHEMICAL FINDINGS
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 1. BLOOD PICTURE AND RED
CELL INDICES
i) Haemoglobin
•The essential feature is a fall in haemoglobin
concentration up to a variable degree.

ii) Blood picture

•The blood picture shows hypochromic
anaemia which may be microcytic, or there
may be some normocytic red cells as well
(dimorphic).
Dr. PRIYANKA SACHDEV
iii) Absolute values
•Absolute values (MCV, MCH and MCHC)
are reduced in hereditary type but MCV is
often raised in acquired type.

iv) Reticulocyte count

•The reticulocyte count is generally low.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 2. Bone marrow

i) Marrow cellularity

•The marrow cellularity is increased due to

erythroid hyperplasia

•Myeloid-erythroid ratio decreased

Dr. PRIYANKA SACHDEV
ii) Erythropoisis → Bone marrow examination shows
erythroid hyperplasia with usually macronormoblastic
erythropoiesis.

• iii) Marrow iron

• Marrow iron stores are raised
• Pathognomonic ring sideroblasts are present.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 3. Biochemical findings
i. Serum iron is usually raised with almost
complete saturation of TIBC.

ii. Serum ferritin levels are raised

iii. Transferrin saturation is increased

iv. Total iron binding capacity (TIBC) is normal

33%
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 OVERVIEW
•Introduction
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment
Dr. PRIYANKA SACHDEV
Differential diagnosis of microcytic
hypochromic anemia

1. Iron deficiency anemia

2. Anemia of chronic disease
3. Thalassemia
4. Sideroblastic anemia
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 OVERVIEW
•Introduction
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment Dr. PRIYANKA SACHDEV
 TREATMENT
1. Focussed on removal of the offending
agent.
2. No definite treatment is available for
hereditary and idiopathic types of
3. However, pyridoxine is administered
routinely to all cases of sideroblastic
anaemia (200 mg per day for 2-3 months).
4. Blood transfusions and other supportive
therapy are indicated in all patients.
Dr. PRIYANKA SACHDEV
 OVERVIEW
•Introduction
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment Dr. PRIYANKA SACHDEV
PATHOPHYSIOLOGICAL
CLASSIFICATION

Dr. PRIYANKA SACHDEV

POLLS 4

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PATHOPHYSIOLOGICAL
CLASSIFICATION

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ANAEMIA OF CHRONIC DISORDERS

Dr. PRIYANKA SACHDEV

 OVERVIEW
•Introduction
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment Dr. PRIYANKA SACHDEV
 Introduction
•In patients of a variety of chronic systemic
diseases in which anaemia develops secondary to
a disease process but there is no actual invasion
of the bone marrow.

•The severity of anaemia is usually directly related

to the primary disease process.
•The anaemia is corrected only if the primary
disease is alleviated

Dr. PRIYANKA SACHDEV

 OVERVIEW
•Introduction
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment Dr. PRIYANKA SACHDEV
ETIOLOGY

Dr. PRIYANKA SACHDEV

 OVERVIEW
•Introduction
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment Dr. PRIYANKA SACHDEV
PATHOGENESIS

Dr. PRIYANKA SACHDEV

 CHRONIC DISORDERS

Proinflammatory cytokines (IL 6, IFN, IL-1, TNF)

Decreased synthesis of erythropoietin Increased synthesis of hepicidin

E. precursors do not proliferate Inhibits ferroportin

Defective erytheopoisis reduces the transfer of iron from

storage pool to E. precursors

Increased stores of iron

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 OVERVIEW
•Introduction
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment Dr. PRIYANKA SACHDEV
 LABORATORY FINDINGS
1. BLOOD PICTURE AND RED CELL
INDICES

2. BONE MARROW FINDINGS

3. BIOCHEMICAL FINDINGS
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 1. BLOOD PICTURE AND RED
CELL INDICES
i) Haemoglobin
•The essential feature is a fall in haemoglobin
concentration up to a variable degree.

ii) Blood picture

•generally normocytic normochromic but may
have slight microcytosis and hypochromia
Dr. PRIYANKA SACHDEV
iii) Absolute values
• MCHC is slightly low.

iv) Reticulocyte count

• The reticulocyte count is generally low.

Dr. PRIYANKA SACHDEV

 2.Bone marrow
i) Marrow cellularity

•The marrow cellularity is increased due to

erythroid hyperplasia
•Myeloid-erythroid ratio decreased

ii) Erythropoisis → Normal erythroid maturation

iii) Bone marrow iron →Increased

Dr. PRIYANKA SACHDEV
 3.Biochemical findings
i. Serum iron is characteristically reduced

ii. Serum ferritin levels are increased in these

patients and is the most distinguishing feature
between true iron-deficiency anaemia and
anaemia of chronic diseases

iii. Transferrin percentage saturation decrease

iv. TIBC is normal or decreases

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 4. Others
Other plasma proteins
•Plasma proteins called ‘Acute phase
reactants’ are raised
•Include gamma-globulin, C3, haptoglobin,
a1-antitrypsin and fibrinogen.
• Elevation of these proteins is responsible
for raised ESR
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 OVERVIEW
•Introduction
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment Dr. PRIYANKA SACHDEV
Differential diagnosis of microcytic
hypochromic anemia

1. Iron deficiency anemia

2. Anemia of chronic disease
3. Thalassemia
4. Sideroblastic anemia
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 OVERVIEW
•Introduction
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Differential diagnosis
•Treatment Dr. PRIYANKA SACHDEV
 Treatment
•Treat underlying cause

Dr. PRIYANKA SACHDEV

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PATHOPHYSIOLOGICAL
CLASSIFICATION

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Dr. PRIYANKA SACHDEV
MEGALOBLASTIC ANAEMIAS— VITAMIN
B12
AND FOLATE DEFICIENCY

Dr. PRIYANKA SACHDEV

 Introduction
•The megaloblastic anaemias are disorders
caused by impaired DNA synthesis

•Vit B12 and folic acid are required for DNA

synthesis.

•So megaloblastic anaemia is due to deficiency

of vit. B12 and folic acid
Dr. PRIYANKA SACHDEV
 OVERVIEW
• Introduction
• Normal B12 and folic acid absorption
• Etiology
• Pathogenesis
• Clinical features
• Lab diagnosis
• Differential diagnosis
• Treatment
Dr. PRIYANKA SACHDEV
Vit. B12 and folic acid absorption

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 OVERVIEW
• Introduction
• Normal B12 and folic acid absorption
• Etiology
• Pathogenesis
• Clinical features
• Lab diagnosis
• Differential diagnosis
• Treatment
Dr. PRIYANKA SACHDEV
ETIOLOGY

Dr. PRIYANKA SACHDEV

 Vitamin B12 deficiency
1. Decrease intake: Inadequate diet,
vegetarianism.
2. Impaired absorption: Intrinsic factor
deficiency (pernicious anemia, gastrectomy),
intestinal diseases (crohn'sdisease , ileitis, ileal
resection, lymphoma, systemic sclerosis), fish
tapeworm infestation (D. latum), blind loop
syndrome (bacterial overgrowth), diverticuli
of bowel, chronic pancreatitis
3. Increased requirment: Pregnancy,
hyperthyroidism, disseminated cancer.
Dr. PRIYANKA SACHDEV
 Folate deficiency
1. Decrease intake: Inadequate diet, alcoholism ,
infancy.
2. Impaired absorption: Malabsorption state,
intestinal diseases.
3. Increased requirment: Pregnancy, infancy,
disseminated cancer.
4. Others: Hemodialysis, antifolate drugs
(methotrexate, phenobarbitone, phenytoin,
trimethoprim , primidone, triametrene,
azathioprinem).
Dr. PRIYANKA SACHDEV
 Rare causes

•Hereditary orotic aciduria,

hypothyroidism, Di-Gueglielmo
syndrome, congenital dyserythropoietic
anemia, thiamine and pyridoxine
deficiency

Dr. PRIYANKA SACHDEV

 OVERVIEW
• Introduction
• Normal B12 and folic acid absorption
• Etiology
• Pathogenesis
• Clinical features
• Lab diagnosis
• Differential diagnosis
• Treatment
Dr. PRIYANKA SACHDEV
 Pathogenesis
•Vit B12 and folic acid are required for
DNA synthesis.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Inadequate DNA synthesis

Defective nuclear maturation

So cytoplasmic maturation proceeds in advance of nuclear maturation

OR
maturation of the nucleus is lag behind to that of the cytoplasm

Nuclear/Cytoplasmic asynchrony

Formation of megaloblasts and macrocytes

Dr. PRIYANKA SACHDEV
ERYTHROID SERIES

Dr. PRIYANKA SACHDEV

 REMEMBER

•Vit. B12 is also involved in the conversion of

methylmalonyl CoA to succinyl CoA which is
required for the formation of normal
neuronal lipids.

•So, deficiency of vitamin B12 (but not of

folic acid) results in neurological features.
Dr. PRIYANKA SACHDEV
• In the haematopoietic precursors in the bone marrow in which the
maturation of the nucleus is lag behind to that of the cytoplasm.

• Since cell division is slow but cytoplasmic development progresses

normally, the nucleated red cell precursors tend to be larger which
is termed megaloblasts.
• Megaloblasts are both morphologically and functionally abnormal

• Red cells formed from them are also abnormal in shape and size→
Macrocytosis

Dr. PRIYANKA SACHDEV

ERYTHROID SERIES

Dr. PRIYANKA SACHDEV

 OVERVIEW
• Introduction
• Normal B12 and folic acid absorption
• Etiology
• Pathogenesis
• Clinical features
• Lab diagnosis
• Differential diagnosis
• Treatment
Dr. PRIYANKA SACHDEV
 CLINICAL FEATURES
• 1. Anaemia

• 2. Glossitis → the patient has a smooth, beefy, red tongue

• 3. Neurologic manifestations (only in vit.B12 def. Not in

folate def.) →
➢Subacute combined, degeneration of the spinal cord
➢peripheral neuropathy due demyelination of the peripheral
nerves, the spinal cord and the cerebrum.
➢Signs and symptoms include numbness, paraesthesia,
weakness, ataxia, poor finger coordination and diminished
reflexes.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 OVERVIEW
• Introduction
• Normal B12 and folic acid absorption
• Etiology
• Pathogenesis
• Clinical features
• Lab diagnosis
• Differential diagnosis
• Treatment
Dr. PRIYANKA SACHDEV
 LABORATORY FINDINGS
1. BLOOD PICTURE AND RED CELL INDICES

2. BONE MARROW FINDINGS

3. BIOCHEMICAL FINDINGS

4. Special Tests for Cause of Specific Deficiency (vit

B12 or Folic acid)
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 1. BLOOD PICTURE AND RED CELL
INDICES
i) Haemoglobin → Fall below the normal
range.

Dr. PRIYANKA SACHDEV

 ii) Red cells
•Characteristic macrocytosis
•Macroovalocytes (characteristic
festure)
•Anisocytosis
•Poikilocytosis
•Tear drop cells
•Basophilic stippling , Cabott Ring,
Howell-jolly bodies. (Evidence of
defective erythropoiesis)
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
(iii) Reticulocyte count →
• Low to normal in untreated cases.

(iv)Absolute values
• Elevated MCV (above 120 fl) proportionate to the severity of
macrocytosis,
• Elevated MCH (above 50 pg)
• Normal or reduced MCHC (because hemoglobin content in the cell
is increased proportiante to increase in the size of RBC)

Dr. PRIYANKA SACHDEV

ERYTHROID SERIES

Dr. PRIYANKA SACHDEV

(v) Leucocytes
• The total white blood cell count may be reduced.
• Presence of characteristic hypersegmented neutrophils (having
more than 5 nuclear lobes) → First manifestation of megaloblastic
anemia

(vi) Platelets
• Platelet count may be moderately reduced
• Bizarre forms of platelets may be seen.

• As DNA synthesis is impaired in all proliferating cells, pancytopenia

(anemia, leukopenia, thrombocytopenia) may occur.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 REMEMBER
•Earliest and characteristic finding of
megaloblastic anemia is hypersegmented
neutrophils (neutrophils with > 5 lobes).

•Diagnosis is made even if a single neutrophil

with > 6 lobes is seen or > 5% neutrophils
with 5 lobes are seen.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 2. BONE MARROW FINDINGS

i) Marrow cellularity

•Hypercellular → erythroid hyperplasia

•Decreased myeloid-erythroid ratio.

Dr. PRIYANKA SACHDEV

 HSC

Lymphoid stem cells Myeloid (trilineage) stem cells

Prolymphocyte

Granulocyte-monocyte p. Erythroid p Megakaryocytes

T, B and NK cells Neutrophils RBC Platelet

Eosinophils
Basophils
Monocytes
Dr. PRIYANKA SACHDEV
ii) Erythropoiesis
• Erythroid hyperplasia due to characteristic megaloblastic
erythropoiesis.

• Megaloblasts are abnormal, large, nucleated erythroid precursors,

having nuclear-cytoplasmic asynchrony i.e. the nuclei are less
mature than the development of cytoplasm.

• The nuclei are large, having fine, sieve-like and open chromatin that
stains lightly, while the haemoglobinisation of the cytoplasm
proceeds normally or at a faster rate → NUCLEAR maturation lags
behind that of cytoplasm

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
ERYTHROID SERIES

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
iii) Marrow iron
•Prussian blue staining for iron in the
marrow shows an increase in the
number and size of iron granules in the
erythroid precursors

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 3. BIOCHEMICAL FINDINGS

•i) The serum iron and ferritin may be

normal or elevated

•ii) Rise in serum unconjugated bilirubin

and LDH as a result of ineffective
erythropoiesis ie. Erythroid precursors
proliferate in bone marrow, but die before
Dr. PRIYANKA SACHDEV
 4. Special Tests for Cause of
Specific Deficiency

1.Test for vitamin B12 deficiency

2. Test for folate deficiency

Dr. PRIYANKA SACHDEV

TESTS FOR VITAMIN B12 DEFICIENCY

• The normal range of vitamin B12 in

serum is 280-1000 pg/ml

•Values less than 100 pg/ml indicate

clinically deficient stage. Traditional
Dr. PRIYANKA SACHDEV
3 tests→

1.Serum vitamin B12 assay

2. Schilling (24-hour urinary excretion)
test
3. serum enzyme levels
Dr. PRIYANKA SACHDEV
 1.SERUM VITAMIN B12 ASSAY
Assay of vitamin B12 in blood can be
done by 2 methods—

•Microbiological assay
•Radioassay.

Dr. PRIYANKA SACHDEV

 2. SCHILLING TEST (24-HOUR
URINARY EXCRETION TEST)
•Schilling test is done to detect vitamin
B12 deficiency as well as to distinguish
and detect lack of IF and malabsorption
syndrome.

•Radioisotope used for labeling B12 is

either 58Co or 57Co.
Dr. PRIYANKA SACHDEV
 Vitamin B12 deficiency
1. Decrease intake: Inadequate diet,
vegetarianism.
2. Impaired absorption: Intrinsic factor
deficiency (pernicious anemia, gastrectomy),
intestinal diseases (crohn'sdisease , ileitis, ileal
resection, lymphoma, systemic sclerosis), fish
tapeworm infestation (D. latum), blind loop
syndrome (bacterial overgrowth), diverticuli of
bowel, chronic pancreatitis
3. Increased requirment: Pregnancy,
hyperthyroidism, disseminated cancer.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
•3 stages:

Dr. PRIYANKA SACHDEV

 Stage I: Without IF
1. The patient after an overnight fasting is
administered oral dose of 1 mg of radioactively
labelled vitamin B12 (‘hot’ B12)

2. 1 mg of unlabelled vitamin B12 (‘cold’ B12) is given

by intramuscular route; this ‘cold’ B12 will saturate
the serum as well as the tissue binding sites.

3. The patient is kept fasting for a further period of 2

hours, following which urinary excretion of B12 is
estimated
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Interpretation
➢In normal individuals, 24-hour urinary
excretion is >10% of the oral dose of ‘hot’
B12.

➢Patients with B12 deficiency excrete lower

quantity < 10% of ‘hot’ B12 which is further
confirmed by repeating the test as in stage
II given below.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Stage II: With IF

1. If the 24-hour urinary excretion of

‘hot’ B12 is low, the test is repeated
using the same procedure as in stage I
but in addition high oral dose of IF is
administered along with ‘hot’ B12
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Interpretation
➢If the 24-hour urinary excretion of ‘hot’
B12 is now normal (>10% of the oral
dose of ‘hot’ B12 ) → the low value in
first stage of the test was due to IF
deficiency (i.e. pernicious anaemia)

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Stage III: Test for
malabsorption of vitamin B12

1. In conditions causing malabsorption,

the test is repeated after a course of
treatment with antibiotics or anti-
inflammatory drugs.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 Interpretation
➢If the 24-hour urinary excretion of ‘hot’
B12 is now normal (>10% of the oral
dose of ‘hot’ B12 ) → the low value in
first stage of the test was due to
malabsorption

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 3.SERUM ENZYME LEVELS

• Another way of distinguishing whether megaloblastic

anaemia is due to cobalamine or folate is by serum
determination of
1. Methylmalonic acid
2. Homocysteine

➢ In cobalamine deficiency →Both are elevated

➢In folate deficiency → only elevation of
homocysteine and not of methylmalonic acid.
Dr. PRIYANKA SACHDEV
 4. Special Tests for Cause of
Specific Deficiency

1.Test for vitamin B12 deficiency

2. Test for folate deficiency

Dr. PRIYANKA SACHDEV

 TESTS FOR FOLATE DEFICIENCY

•The normal range of serum folate is 6-18

ng/ml.
• Values of 4 ng/ml or less are generally
considered to be diagnostic of folate
deficiency.

Dr. PRIYANKA SACHDEV

•3 tests →

1.Urinary excretion of FIGLU

2.Serum folate
3.Red cell folate assay
Dr. PRIYANKA SACHDEV
 1. URINARY EXCRETION OF FIGLU

• Folic acid is required for conversion of

formiminoglutamic acid (FIGLU) to glutamic
acid in the catabolism of histidine.

•Thus, on oral administration of histidine,

urinary excretion of FIGLU is increased if folate
deficiency is present
Dr. PRIYANKA SACHDEV
 Histidine

Formiminoglutamic acid (FIGLU)

Folic acid

Glutamic acid

Dr. PRIYANKA SACHDEV

 2. SERUM FOLATE ASSAY

•The folate in serum can be estimated by

2 methods—microbiological assay and
radioassay.

Dr. PRIYANKA SACHDEV

 3. RED CELL FOLATE ASSAY

•Red cells contain 20-50 times more

folate than the serum

•Thus red cell folate assay is more

reliable indicator of tissue stores of
folate than serum folate assay.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 OVERVIEW
• Introduction
• Normal B12 and folic acid absorption
• Etiology
• Pathogenesis
• Clinical features
• Lab diagnosis
• Differential diagnosis
• Treatment
Dr. PRIYANKA SACHDEV
 TREATMENT
•Most cases of megaloblastic anaemia need
therapy with appropriate vitamin. This
includes:

1. Hydroxycobalamin as intramuscular
injection 1000 μg for 3 weeks

2. Oral folic acid 5 mg tablets daily for 4

months.
Dr. PRIYANKA SACHDEV
 Response to therapy
• Marrow begins to revert back to normal morphology within
a few hours of initiating treatment and becomes
normoblastic within 48 hours of start of treatment

• Reticulocytosis appears within 4-5 days after therapy is

started and peaks at day 7

• Haemoglobin should rise by 2-3 g/dl each fortnight

• The peripheral neuropathy may show some improvement

Dr. PRIYANKA SACHDEV

POLLS 6

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A

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Dr. PRIYANKA SACHDEV
D

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Dr. PRIYANKA SACHDEV
B

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Dr. PRIYANKA SACHDEV
A

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 A
•MCV > 100fL indicates macrocytosis

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Dr. PRIYANKA SACHDEV
D

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Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
B

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Dr. PRIYANKA SACHDEV
B

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ETIOLOGY

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Dr. PRIYANKA SACHDEV
C

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Dr. PRIYANKA SACHDEV
B

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Dr. PRIYANKA SACHDEV
C

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Dr. PRIYANKA SACHDEV
D

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Dr. PRIYANKA SACHDEV
C

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ETIOLOGY

Dr. PRIYANKA SACHDEV

 Vitamin B12 deficiency
1. Decrease intake: Inadequate diet,
vegetarianism.
2. Impaired absorption: Intrinsic factor deficiency
(pernicious anemia, gastrectomy), intestinal
diseases (crohn'sdisease , ileitis, ileal resection,
lymphoma, systemic sclerosis), fish tapeworm
infestation (D. latum), blind loop syndrome
(bacterial overgrowth), diverticuli of bowel,
chronic pancreatitis
3. Increased requirment: Pregnancy,
hyperthyroidism, disseminated cancer.
Dr. PRIYANKA SACHDEV
PERNICIOUS ANAEMIA

Dr. PRIYANKA SACHDEV

 OVERVIEW
•Introduction
•Etiopathogenesis
•Evidences
•Morphological features
•Clinical features
•Lab diagnosis
•Treatment
Dr. PRIYANKA SACHDEV
 Introduction

•Anaemia due to vitamin B12 deficiency

due to IF deficiency

•Intrinsic factor is secreted from parietal

cells of stomach.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 OVERVIEW
•Introduction
•Etiopathogenesis
•Evidences
•Morphological features
•Clinical features
•Lab diagnosis
•Treatment
Dr. PRIYANKA SACHDEV
 PATHOGENESIS
Autoantibodies against gastric parietal cells

Atrophy of gastric mucosa

Deficiency of IF

Vitamin B 12 deficiency

Pernecious anemia
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
•So pernicious anemia is megaloblastic
anemia due to vit. B12 deficiency ( due
to IF deficiency)

Dr. PRIYANKA SACHDEV

 OVERVIEW
•Introduction
•Etiopathogenesis
•Evidences
•Morphological features
•Clinical features
•Lab diagnosis
•Treatment
Dr. PRIYANKA SACHDEV
 Evidences
1.Associated with other autoimmune diseases such as
Graves’ disease, myxoedema, thyroiditis, vitiligo,
diabetes and idiopathic adrenocortical insufficiency.

2. Patients with PA have abnormal circulating

autoantibodies such as anti-parietal cell antibody
(90% cases)

3.Corticosteroids have been reported to be beneficial

Dr. PRIYANKA SACHDEV

 OVERVIEW
•Introduction
•Etiopathogenesis
•Evidences
•Morphological features
•Clinical features
•Lab diagnosis
•Treatment
Dr. PRIYANKA SACHDEV
 MORPHOLOGIC FEATURES
• The most characteristic pathologic finding in PA is
gastric atrophy

• Intestinalization of stomach (replacement of gastric

mucosa by muscus-secreting globlet cells)

• All features of megaloblastic anemia→Other changes

are secondary to vitamin B12 deficiency and include
megaloblastoid alterations in the gastric and intestinal
epithelium and neurologic abnormalities such as
peripheral neuropathy and spinal cord damage
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
•Pernicious anemia is associated with
increased risk of gastric cancer

Dr. PRIYANKA SACHDEV

 OVERVIEW
•Introduction
•Etiopathogenesis
•Evidences
•Morphological features
•Clinical features
•Lab diagnosis
•Treatment
Dr. PRIYANKA SACHDEV
 Clinical features

•Same

Dr. PRIYANKA SACHDEV

 Lab diagnosis

•Same → Schilling test

Dr. PRIYANKA SACHDEV

 TREATMENT

•1. Parenteral vitamin B12 replacement

therapy.
•2. Symptomatic and supportive therapy
such as physiotherapy for neurologic
deficits
•3.Corticosteroid therapy can improve the
gastric lesion
Dr. PRIYANKA SACHDEV
 POLLS 7

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Dr. PRIYANKA SACHDEV
B

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Dr. PRIYANKA SACHDEV
A

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PATHOPHYSIOLOGICAL
CLASSIFICATION

Dr. PRIYANKA SACHDEV

 APLASTIC ANAEMIA
•Aplastic anaemia result from aplasia of the
bone marrow

•In aplastic anaemia, there is pancytopenia i.e.

simultaneous presence of
1. Anaemia
2. Leucopenia
3. Thrombocytopenia
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
ETIOLOGY

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PATHOGENESIS

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
 Aplasia of the bone marrow

Sufficient reduction in the number of haematopoietic

pluripotent stem cells

Lower counts of all the three blood cells types

i) Red blood cells (anemia, reticulocytopenia
ii) WBCs (leukopenia/ neutropenia(PGI05))
iii) Platelets (thrombocytopenia)

PANCYTOPENIA
Dr. PRIYANKA SACHDEV
 OVERVIEW
•Introduction
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Treatment
Dr. PRIYANKA SACHDEV
 CLINICAL FEATURES
• 1. Anaemia → mild progressive weakness and fatigue.

• 2. Thrombocytopenia → Haemorrhage from various sites

due to such as from the skin, nose, gums, vagina, bowel,
and occasionally in the CNS and retina.

• 3. Leucopenia →Infections of the mouth and throat are

commonly present.

• 4. The lymph nodes, liver and spleen are generally not

enlarged.
Dr. PRIYANKA SACHDEV
 LABORATORY FINDINGS

1. BLOOD PICTURE
2. BONE MARROW PICTURE

Dr. PRIYANKA SACHDEV

 BLOOD PICTURE
i) Haemoglobin → Fall below the normal
range.

ii) Red cells → The blood picture generally

shows normocytic normochromic anaemia

iii)The reticulocyte count is reduced or zero.

Dr. PRIYANKA SACHDEV
iv) WBC → Leucopenia The absolute
granulocyte count is particularly low
(below 1500/μl) with relative
lymphocytosis.

v) Platelet → Thrombocytopenia
Dr. PRIYANKA SACHDEV
 BONE MARROW
i) Cellularity →

• A bone marrow aspirate may yield a ‘dry tap’.

• A trephine biopsy is generally essential for making the
diagnosis which reveals patchy cellular areas in a
hypocellular or aplastic marrow due to replacement by
fat.
• Haematopoietic stem cells bearing CD34 marker are
markedly reduced or absent.
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
Dr. PRIYANKA SACHDEV
 OVERVIEW
•Introduction
•Etiology
•Pathogenesis
•Clinical features
•Lab diagnosis
•Treatment
Dr. PRIYANKA SACHDEV
 PRINCIPLES OF TREATMENT
A. General management

•1. Identification and elimination of the

possible cause

•2. Supportive care consisting of blood

transfusions, platelet concentrates, and
treatment and prevention of infections
Dr. PRIYANKA SACHDEV
B. Specific treatment

1. Marrow stimulating agents such as androgen may be

administered orally.

2. Immunosuppressive therapy with agents such as

antithymocyte globulin and anti-lymphocyte serum has been
tried with 40-50% success rate.

Dr. PRIYANKA SACHDEV

3. Bone marrow transplantation

• Considered in severe cases under the age of 40 years where

the HLA and mixed culturematched donor is available.

• Complications of bone marrow transplantation such as severe

infections, graft rejection and graft-versus-host disease
(GVHD) may occur

Dr. PRIYANKA SACHDEV

 REMEMBER
•Aplastic anemia → Pancytopenia with
hypocellular bone marrow

Dr. PRIYANKA SACHDEV

 Other causes of pancytopenia
Pancytopenia with hypocellular bone
marrow:
•Aplastic anemia

Dr. PRIYANKA SACHDEV

Pancytopenia with hypercellular marrow:
• Myelodysplasia
• PNH
• Myelofibrosis
• hairy cell leukemia
• megaloblastic anemia
• bone marrow lymphoma
• SLE
• Hypersplenism
• Sarcoidosis
• alcohol
Dr. PRIYANKA SACHDEV
 MYELOPHTHISIC ANAEMIA
•Development of pancytopenia due to
infiltration of the marrow termed as
myelophthisic anaemia.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
• 1. Haematologic malignancies (e.g. leukaemia, lymphoma,
myeloma).

• 2. Metastatic deposits from non-haematologic malignancies

(e.g. cancer breast, stomach, prostate, lung, thyroid).

• 3. Advanced tuberculosis.

• 4. Primary lipid storage diseases (Gaucher’s and Niemann-

Pick’s disease).

Dr. PRIYANKA SACHDEV

ETIOLOGY

Dr. PRIYANKA SACHDEV

PURE RED CELL APLASIA (PRCA)
•Pure red cell aplasia (PRCA) is a rare
syndrome involving a selective failure in the
production of erythroid elements in the
bone marrow but with normal
granulopoiesis and megakaryocytopoiesis.

•Patients have normocytic normochromic

anaemia and reticulocytopenia with normal
WBC and platelet count.
Dr. PRIYANKA SACHDEV
CAUSES

Dr. PRIYANKA SACHDEV

1.Congenital PRCA (Blackfan-
Diamond syndrome)

•It is a rare chronic disorder detected at

birth or in early childhood.
•It occurs due to mutation in a ribosomal
RNA processing gene termed as RPS19
•The disorder is corrected by marrow
transplantation.
Dr. PRIYANKA SACHDEV
 2. Acquired PRCA
•Thymoma (most common)
•Connective tissue diseases (SLE,
rheumatoid arthritis),
•Lymphoid malignancies (lymphoma, T-
cell chronic lymphocytic leukaemia)

Dr. PRIYANKA SACHDEV

3. Chronic B19 parvovirus infections

•B19 parvovirus produces cytopathic

effects on the marrow erythroid
precursor cells and are characteristically
seen as giant pronormoblasts.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
PATHOPHYSIOLOGICAL
CLASSIFICATION

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Dr. PRIYANKA SACHDEV
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 C
• PNH is the only hemolytic anemia caused by an acquired
intrinsic defect in the cell membrane. PNH arises in the setting
of aplastic anemia and these patients are at increased risk of
developing acute myelogenous leukemia.

• Aplastic anemia may progress to PNH and MDS.

Dr. PRIYANKA SACHDEV

Dr. PRIYANKA SACHDEV
A

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D

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