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“The future belongs to

those who believe in the


beauty of their
dreams.”
–Eleanor Roosevelt
“No doubt knowledge is
valuable..”,
but above it are power,
goodness & most important
Character”
HEMATOLOGY

Anemia
Dr. Venkatesh M. Shashidhar
Associate Professor of Pathology
Fiji School of Medicine
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Normal Blood Cells:

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Blood Smear - Normal

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Haemopoiesis:

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Steps in Erythropoisis

Early Intermediate Late

Proerythroblast Polychromatophilic Reticulocyte


(Pronormoblast) Normoblast
Basophilic Orthochromatophilic Erythrocyte
Normoblast Normoblast

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RBC disorders (Anemias) :

“Anemia is decreased red cell


mass affecting tissue
oxygenation”
• Practical - Low Hb* or Low Hematocrit*

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C.B.C
• Haemoglobin - 15±2.5, 14 ±2.5 - g/dl
• PCV - 0.47 ±0.07, 0.42 ±0.05 - l/l (%)
– Haematocrit, effective RBC volume - better
• RBC count - 5.5 ±1, 4.8 ± 1 x1012/l
• MCHC - Hb/PCV - 30-36 - g/dl
– Hb synthesis within RBC
• MCH - Hb/RBC - 29.5 ± 2.5 pg/l
– Average Hb in RBC
• MCV - PCV/RBC 85 ± 8 - fl

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Mechanism of Anemia :
• Decreased Production:
– Nutrient Deficiency.
• Iron, B12/Folate
– Hemopoietic cell damage:
• Aplastic, Hypoplastic – Neoplasms, radiation,
drugs
• Increased loss / destruction:
– Blood loss anemias - parasites, bleeding
– Hemolytic anemias – Autoimmune,
mechanical, drugs, parasites.
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Iron Deficiency Anemia:

• Most abundant metal but most common


deficiency..!
• Common in developing world,
• Parasitic Worm infestation + Malnutrition
• Chronic blood loss  only Iron Deficiency
• not other deficiency….. Why ?

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Iron Metabolism
• Limited absorption* and no proper excretory mech*.
• Recycling of iron – dead cells to new cells
• 1mg/day  3-6G body  1mg/day
• 10% of the 10 to 20 mg of dietary iron.
• Iron is absorbed in Jejunum.
• Stored as Ferritin & Hemosiderin.
• Laboratory tests:
• Serum iron(1mg/l)
• Serum iron binding capacity (3mg)
• Serum ferritin (>20ug)
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Transferrin

✹Transport Protein For Iron In Blood


✹Fully Saturated Transferrin = TIBC
300 - 350ug/dl Fe
✹Normal Transferrin - 1/3 Filled With Iron
100 - 120ug/dl Fe (Serum Iron)
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IDA - Etiology

• Blood loss
– Bleeding – Parasites, Gynecologic, ulcers…
• Increased need
– Pregnancy, children
• Poor diet / poor absorption
– Malnutrition (greens & meat),
malabsorption, intestinal surgery, gastric
atrophy.

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IDA - Pathogenesis:
• Decreased Iron stores
• Decreased Hb Synthesis
• Delayed maturation of erythroblasts
(cytoplasmic)
• Decreased cytoplasm, more division
(microcytes)
• Decreased hb content (hypochromia)
• Anemia.
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Microcytic Anemia (IDA)
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Clinical Features:
• General features of Anemia
– Pallor, Weakness, Lethargy,
– Breathlessness on exertion
– Palpitations  heart failure  pedal edema
• Special features in IDA:
– Angular cheilitis, atrophic glossitis,
– Oesophageal atrophy/web  dysphagia,
– Koilonychia, brittle nails, gastric atrophy.
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Angular cheilitis

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Angular cheilitis & Glossitis

…Why?

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Koilonychia in Iron def.

…Why?

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Koilonychia in Iron def.

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Hypochromic Microcytic RBC

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Iron Deficiency Anemia:

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IDA on Treatment :

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“Seeing much, suffering much and


studying much are the three
pillars of learning.”
–Benjamin Disraeli

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Megaloblastic anemia:

• Vitamin B12/Folic acid deficiency


• Second most common type of anemia.
• Multi System disease – All organs with
increased cell division.
• Macrocytic anemia, pancytopenia.
• Pernicious anaemia –
– autoimmune, Gastric atrophy, VitB12 def.

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Megaloblastic anemia - Etiology

• Malnutrition
• Intrinsic factor Ab - Pernicious anemia
• Gastrectomy, Ileal resection
• Inflammatory bowel disease
• Malabsorption syndromes - Sprue
• Blind loop syndrome

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Megalobl - Pathogenesis:
• Decreased Vit B12 / Folate
• Decreased DNA Synthesis
• Delayed maturation of erythroblasts (Nucleus)
• Increased cell size (macrocytes)
• Normal hb content (Normochromia)
• Decreased RBC number
• Decreased WBC number (pancytopenia)
• Anemia & Pancytopenia.

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Vitamin B12 Absorption

B12

B12 Parietal cells -


Stomach produce IF
IF

BIF
12+IF
Ileum -
IF receptors
B12
IF
B12
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Macrocytic Anemia (Meg.):

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CWM-20353-Meg.An

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Macroovalocytes & Macropoly

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Megaloblastic Anemia :

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CWM-20353-Meg.An

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“The only person who never


makes a mistake is a person who
never does anything”

- Theodore Roosevelt

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Congenital RBC Disorders:


• Membrane Disorders:
– Spherocytosis, Elliptocytosis
• Hemoglobin Disorders:
– Hemoglobinopathies - Sickle cell, HbC etc.
– Thalassemia Syndromes - α, β, δ
• Enzyme disorders:
– G6PD, PK deficiency

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Differential diagnosis of
Anemia
Low Hb=Anemia
MCV

Low Normal High


microcytic normocytic macrocytic

Measure Ferritin Measure B12 + folate

Low Normal/high Normal Low


Megaloblastic
Anemia of anemia
Iron def
chronic disease/
Anemia
Congenital Hb dis.
Reticulocyte count

Hemolytic anemia or high low Anemia of chronic disease


blood loss Renal failure
Marrow failure
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Anemia with Low MCV and Low Retics

• Differential diagnosis
• Iron deficiency (Micro Hypo - severe)
• Anemia of chronic disease (mild micro/hypo)
• Laboratory evaluation
• Iron, iron-binding capacity, and ferritin
• Blood smear – Micro/hypo, Pencil cells.

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Anemia with High MCV


• Differential diagnosis
• Megaloblastic anemia – B12, Folate
• Nonmegaloblastic anemia – No def.
• High retics – bleeding, hemolysis *
• Laboratory evaluation
• Serum B12, RBC folate levels.
• Blood film – macroovalocytes, pancytopenia
• Bone marrow – dysplasia, neoplasia.
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Anemia with Normal MCV


• Differential diagnosis
• Primary bone marrow failure
– Aplastic anemia, drugs, chemotherapy
• Secondary bone marrow failure
– Uremia, Endocrine disorders, AIDS,
– Anemia of chronic disease
• Laboratory evaluation
• Blood smear & Iron, TIBC, Ferritin.
• Bone marrow smear and iron stores
• Kidney, Thyroid & liver function tests, Cortisol levels
• Erythropoietin level
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Anemia with high Retics


• Differential diagnosis:
– Bleeding – blood loss internal/external
– Hemolysis – immune, mechanical, toxic, inf.
• Laboratory evaluation
• Blood film, nRBC, spherocytes, Parasites, Retics.
• Hemolysis – indirect Bilirubin, Haptoglobin,
• Direct and indirect Coombs test
• Hemoglobin electrophoresis, G6PD screen etc.

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Bone Marrow Cellularity:

Normal Hypercellular Hypocellular

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ß Thalassemia Major:

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Sickle Cell Disease:

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Polychromasia - Hemolytic An.

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Warm Ab IHA:

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Microangiopathic Hemolytic A.

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Thalassemia Trait:

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Thalassemia Major:

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Her. Spherocytosis:

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Hereditary Elliptocytosis:

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G6PD Deficiency Anemia:

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Causes of High Hct/polycythemia


• Relative or spurious erythrocytosis
– Hemoconcentration secondary to dehydration
– (diarrhea, diaphoresis, diuretics, deprivation of
water, emesis, ethanol, etc.)
• Absolute erythrocytosis (True ):
– Tissue hypoxia – Smoking (Co), High
altitude, Pumonary disease, respiratory def.
Cardiac shunts, High oxygen-affinity Hb.
– High EPO - Tumors eg. HCC.
– Androgen therapy
– Primary - Polycythemia vera Shashi-May 04
The only person who
never makes a mistake
is the person who never does
anything…!
- Theodore Roosevelt

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