Anemia is defined as a reduction of the total

Objectives

 Anemia: Definition & epidemiology

 Iron deficiency anemia (IDA)

 Definition

 Iron in body

 Causes of IDA

 How to diagnose IDA by:

1. History (symptoms)

2. Examination (signs)

3. Investigation

 Management

 prevention

ANAEMIA



Anemia is defined as a reduction of the total

circulating red cell mass below normal limits.



Anemia reduces the oxygen-

carrying capacity of the blood,

leading to tissue hypoxia.

WHO CRITERIA FOR ANEMIA



Adult Male - Hb < 13g/dl



Adult female - Hb < 12g/dl



Children <12 yrs - Hb < 11 g/dl



Pregnant female - Hb < 11g/dl

• Nutritional or non – Nutritional

• Etiological classification

• Morphological classification

Classification of anemia

Anemia can be classified as:



Nutritional: iron, vitamin B12, or folic acid.



Non-nutritional: due to decreased

development of RBC precursors,

blood loss, decreased formation, or

increased destruction of RBCs.

Also Anemia can be classified by using two basic approaches:



Etiology (mechanism): the causes of erythrocyte and hemoglobin depletion



Morphology: the characteristic

changes (size, shape, and color)

in the erythrocytes

Morphological classification

 Microcytic hypochromic anemia –

 Iron deficiency anemia

 Thalassemia

 Sideroblastic anemia

 Lead poisoning

 Normocytic anemia –

 Acute hemorrhage

 Anemia of chronic disorder

 Macrocytic anemia –

 Vit B12 def, folic acid def, pernicious anemia, anemia of alcoholism

Causes of Anemia (etiological classification)

I. Decreased production of Red Cells

A. Disturbance of proliferation and differentiation of stem cells (aplastic anemia, tumor infiltration)

B. Disturbance of proliferation and maturation of erythroblasts

1. Defective DNA synthesis (megaloblastic anemia)

1.

Defective hemoglobin synthesis

a) Deficient in heme synthesis (iron deficiency anemia)

b) Deficient in globin synthesis

(thalassemia)

Decreased production of Red Cells (contd..)

B. Bone marrow suppression (drugs, chemotherapy, irradiation).

C. Low levels of trophic hormones which stimulate RBC production, such as erythropoeitin (anemia

Causes of Anemia

II. Increased RBC destruction (Hemolytic anemia)

• Inherited hemolytic anemias (eg,

hereditary spherocytosis, sickle cell disease, thalassemia major)

• Acquired hemolytic anemias

(autoimmune hemolytic anemia,

thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, malaria)

Causes of Anemia

III. ^{Blood loss}

 Acute / chronic blood loss (hemorrhagic)

• Obvious bleeding (trauma, melena, hematemesis, menometrorrhagia)

• Occult bleeding (slowly bleeding ulcer or carcinoma).

• Induced bleeding (repeated diagnostic testing, hemodialysis losses, excessive blood donation)

Anemia distribution

•Most common nutritional disorder worldwide

•Most common single cause of anemia worldwide,

accounting for about half of all anemia cases.

•Prevalence higher in developing country

Iron deficiency anemia is -

IDA Epidemiology

 IDA prevalence in India – 35 - 45% (among childrens)

 56% adolescent girls & 30% 0f boys are anemic in India

Anemia Preschool children

Pregnant female

Non -

pregnant Global

burden

47.4% 41.8% 30.2%

SE Asia 65.5% 48.5% 45.7%

India 74.3% 49.7% 52%

Definition



Iron deficiency is defined as a

decreased total iron body content.



Iron deficiency anemia occurs when iron deficiency is sufficiently severe to diminish erythropoiesis and cause the development of anemia.



Iron deficiency without anemia are

more common

Iron in the body



Stored in two form –



Hemosiderin – brown pigment in RE cells in BM, spleen & liver.

+ve prussian blue reaction



Ferritin – serum ferritin level

reflect the iron store

Functions of Iron

1. Formulation of hemoglobin

2. Binding O2 to RBC and transport

3. Formulation of cytochrome myoglobin

4. Regulation of Body temperature

5. Muscle activity

6. Catecholamine metabolism

7. Immune system

8. Brain Development & function

9. Thyroid function

 Heme iron vs non heme iron

 About 20% of heme iron is absorbable

 In contrast only 1% to 2% of non-heme iron

 The total body iron content is normally

about 2 gm in women and as high as 6 gm in men (≈ 4 gm)

 About 80% of the functional iron is found in hemoglobin;

 Rest in myoglobin and iron-

containing enzymes such as catalase and the cytochromes contain the

rest.

 The storage pool represented by hemosiderin and ferritin contains about 15% to 20% of total body iron.

Iron

balance

is maintained largely by

regulating

absorption

of dietary

iron in the

proximal

duodenum

LIP

e^- Fe³⁺

ferritin

e^-

Tf

Fe³⁺ Fe³⁺

Fe²⁺

HO DMT1

Fe²⁺ IREG1 Hp

Fe²⁺

Dcytb

Fe³⁺

Gut lumen

Plasma

Duodenal iron transport

heme HCP1

IREG-1

ferroporetin

e^- Red

Oxi

IRON METABOLISM

Promoters and inhibitors of non-heme iron absorption



Promoters:

Ascorbic acid Meat

Citric Acid

Some spices

-carotene Alcohol



Inhibitors:

Phytic acid Polyphenols Tannins

Calcium



Fe is transported in plasma by an iron- binding glycoprotein called transferrin



In normal individuals, transferrin is about one third saturated with iron,



Iron is always transported in ferric form



Stored in Liver, spleen etc. as Ferritin

or Haemosiderin



Since plasma ferritin is derived largely from the storage pool of

body iron, its levels correlate well with body iron stores. In iron

deficiency, serum ferritin is always below 12 µg/l, whereas in iron

overload values approaching 5000

µg/l can be seen

Transportation of iron

TfR

Diet

1-Poor intake 2-Vegetarians

Malabsorption of iron

 chronic diseases

1. celiac syndrome

2. atrophic gastritis

3. Helicobacter pylori

gastritis



Gastrectomy



surgical

removal of the proximal small bowel



Prolonged achlorhydria



Congenital iron

deficiency

Increased demand

 Growing adolescents

 Pregnancy and lactation

Blood Loss



Major cause … overt or occult



Chronic blood loss from

1.

Heavy Menstruation

2.

history of bleeding (hematuria, hematemesis, hemoptysis,

Hematochezia )

 Hemorrhoids

 Hookworm infestation

From erosion

associated with :

 peptic ulcer

 Non steroidal anti

inflammatory drugs

 neoplastic disease

Iatrogenic Blood loss

1. repeated blood donations

2. post-operative blood loss

3. repeated and massive blood drawing in

complicated

medical condition

Clinical Features

 Symptoms depend on how rapidly the anaemia develops.

 In cases of chronic, slow blood loss,

adaptation to tolerate extremely low Hb concentrations even upto 7.0 g/dL, with remarkably few symptoms.

 lethargy and dyspnoea common

symptoms. Unusual symptoms are

headaches, tinnitus and taste disturbance.

 Pica - eating of dirt, chalk, soap, etc.,

On Examination

 Pallor

 Nail changes such as koilonychia (spoon-shaped nails) may result in brittle, flattened nails.

 Angular stomatitis, in which painful cracks appear at the angle of the

mouth, sometimes accompanied by glossitis.

Pallor

koilonychia

Angular Stomatitis

Glossitis or Inflammation of the tongue in which papillae are lost and the surface appears smooth,

Other Clinical Features:



Oesophageal and pharyngeal webs, (uncommon especially in middle aged female presenting with dysphagia).

- Due to, reduction in Iron

containing enzymes in the

epithelial and GI tract.

 Esophageal webs appear together with microcytic-hypochromic

anemia and atrophic glossitis to complete the triad of major

findings in the rare

Plummer- Vinson syndrome

 Tachycardia and cardiac failure may occur with severe anemia irrespective of cause.

Investigation

 CBC

1. Low HGB

2. Low MCV

3. Low MCH

4. Low MCHC

5. High/normal platelet

6. Normal WBC

7. Low reti count

Peripheral smear

 microcytic and hypochromic red blood cells

 Platelets usually normal/high

 anisocytosis and poikilocytosis

 target cells and pencil cells

Target cells

Pencil cells

Iron profile

 Serum ferritin - Deplete first diagnostic of Iron deficiency

 Serum iron - Decrease

 Total iron-binding capacity (TIBC) - Increase

 Transferrin saturation % ⁼

(Serum iron/TIBC ) x 100 -- decreased

**So low serum Fe, low ferritin, high

TIBC (including elevated transferrin level and reduction in transferrin saturation

<15%) – Hall mark of IDA

Reference range Iron profile

(Practical Hematology – Dacie & Lewis)

Male Female

Serum Iron 13 – 32 µmol/l (0.7 – 1.8 mg/l)

13 – 32 µmol/l (0.7 – 1.8 mg/l) TIBC 45 – 70 µmol/l

(2.5 – 4.0 mg/l )

45 – 70 µmol/l (2.5 – 4.0 mg/l ) Transferrin 1.2 – 2.0 g/l 1.2 – 2.0 g/l

Serum ferritin 20 – 300 µg/l 15 – 150 µg/l

% saturation Tf 20 – 50% 20 – 50 %

Note - 1 mg of transferrin bind with 1.4 µg iron

Bone marrow aspirate

the "gold standard" test for estimating iron stores

 Erthroid hyperplasia with micronormoblast

 Iron depletion

Micronormoblast – basophilic

cytoplasm with fraying of cytoplasm

border

( a) Normal bone marrow showing plentiful iron in

macrophages (Perls stain) with iron

granules in

erythroblasts (insets).

(b) Iron deficiency:

bone marrow

showing absence of stainable iron

(Perls stain).

Stages of iron deficiency

•Low ferritin

•Absent bone marrow iron

Depleted iron stores asymptomatic

Stage 1

•Low transferrin saturation

•Low serum iron

•Raised serum transferrin

•Normal hemoglobin Latent iron

deficiency Stage

2

•Low hemoglobin

•Low hematocrit Iron deficiency

anemia Stage

3

Management

1. Treatment of the cause

2. Iron replacement

 Oral iron

 Parenteral iron

the hematological response to parenteral iron treatment is not faster than the response to oral iron

 Blood transfusion

Prevention

The Centers for Disease Control and Prevention (CDC) has developed new guidelines for

preventing and controlling iron deficiency based upon age and sex

1. For girls ages 12 to 18 and nonpregnant women of childbearing age screening every 5 to 10

years, annual screens for women with risk

factors for iron deficiency. A positive test should be repeated to confirm

2. Pregnant women should begin taking oral iron at the first prenatal visit as primary prevention

3. Men and postmenopausal women do not need routine screening for iron deficiency