ANEMIA

Dr. Mansour Aljabry

Head of Flow cytometry unit
Assistant professor & Consultant Hematologists
Hemoglobin??
 Hemoglobin structure

Globin chain

O2
O2 β α
⁺⁺Fe ⁺⁺Fe Haem

⁺⁺Fe Prophyrin ring

Iron atom ⁺⁺Fe
α β O2
O2

Dr. Aljabry
 Hemoglobin

• Hemoglobin is the protein molecule in RBC that carries O2

from the lungs to the body's tissues and returns carbon CO2
from the tissues back to the lungs.
• Hemoglobin maintains the shape of RBC also.
 Hematopoiesis

Hematopoietic stem cell:

Myeloid SC Erythroid Precursors
1- Self renewal
2- Cell differentiation

Erythropoietin
Transcriptional GATA1
Factor
 Erythropoiesis

The “Bone Marrow” is the major site with the need of:
Folic acid – Iron “Ferrous” – Vit B12 – Erythropoietin -Amino acids
minerals - other regulatory factors

Basophilic Intermediate Late

Erythroblast Reticulocyte Erythrocyte
Normoblast Normoblast Normoblast

+ ++ +++ ++ + -
Synthesis of
6 Hemoglobin 6
 Normal Ranges
HCT
Female Male Indices
11.5-15.5 13.5-17.5 Hemoglobin(g/dL)
36-48 40-52 Hematocrit (PCV) (%)
3.9-5.6 4.5-6.5 Red Cell Count (×10¹²)
80-95 Mean Cell Volume (MCV) (fL)
30-35 Mean Cell Hemoglobin (MCH)
(pg)

Hb MCV MCH

Microcytic
Hypochromic

Normocytic

Macrocytic Normochromic
 ANEMIA

• An (without) -aemia (blood)

• Reduction of Hb concentration below the normal
range for the age and gender
• Leading to decreased O2 carrying capacity of
blood and thus O2 availability to tissues (hypoxia)
 Clinical Features

Presence or absence of clinical feature depends on:

1-Speed of onset :
Rapidly progressive anemia causes more symptoms than slow onset
anemia due to lack of compensatory mechanisms:
(cardiovascular system, BM &O2 dissociation curve

2-Severity:
• Mild anemia :no symptoms usually
• Symptoms appear if Hb less than 9g/dL

3- Age:
• Elderly tolerate anemia less than young patients
 Clinical Features
General features of anemia-1

• Weakness
• Headache
• Pallor Related to anemia
• Lethargy
• Dizziness
• Palpitation (tachycardia)
• Related to compensatory
Angina
mechanism
• Cardiac failure

2-Specific features

Specific signs are associated with particular types of anemia :

 Spoon nail with iron deficiency,
 Leg ulcers with sickle cell anemia
 Jaundice with hemolytic anemia
 bone deformities in thalassemia major
Classification of
Anemia
 Hemoglobin DNA RBC count

Prophyrin DNA Blood loss

synthesis
Iron Hemolysis
Globin chain RBC production

Acute
bleeding
Thalassemia Megaloblastic Autoimmune BM failure:
anemia: Enzymopathy -Chemotherapy
Iron def. Membranopathy -Aplastic anemia
anemia -B12 def.
Mechanical -Malignancy
Sidroblastic -Folate def. Anemia of chronic
Sickle cell anemia
anemia MDS disease

Hypochromic Macrocytic Normocytic

microcytic anemia normochromic
anemia anemia
 Iron Deficiency Anemia

• Iron is among the abundant minerals on earth (6%).

• Iron deficiency is the most common disorder( 24%). !
• Limited absorption ability :
1-Only 5-10% of taken iron will be absorbed
2- Inorganic iron can not be absorbed easily.

• Excess loss due to hemorrhage

 Daily absorption ≈1 mg

Macrophage (1g)
Transferrin (4mg)

Liver and muscle

Storage forms: myoglobin (650mg)
Ferritin
Haemosiderin
Bone marrow
erythroblast
(150mg)

Urine
Circulating
faeces
hemoglobin
Skin Daily loss ≈1 mg
(2.5g)
nail
hair

menstrual loss
(hemorrhage)
14 02/09/2023
 Hypoxia
IL6
Tfr2

+ve

Hepcidin
- ve

Iron for
erythropoeisis

BM macrophage
 Iron Absorption

Factor reducing absorption Factors favoring absorption

Inorganic iron Haem iron

Ferric iron Fe+++ Ferrous Iron (Fe++)

Alkalines Acid

Iron overload Iron def

Tea Pregnancy

Increased hepcidin Hemochromatosis

Precipitating agent(phenol) Solubilizing agent (Sugar)

 Iron Absorption
1-Body Iron status:
Increased demands Low iron stores high absorption
(iron def.,pregnancy..)

Iron overload Full iron stores Low absorption

2- Content and form of dietary iron

More Iron
More
Heam Iron
absorption
Ferrous Iron
3- Balance between dietary enhancers&Inhibitory factors:
Enhancers Inhibitors
Meat (haem iron) Dairy foods (calcium)
Fruit (Vitamin C) High fiber foods (phytate)
Sugar (Solubilizing agent ) Coffee &tea (polyphenoles)
Acids Anti -Acids
 Causes of IDA

1-Chronic blood loss:

• GIT Bleeding: peptic ulcer, esophageal varices , hookworm cancer
• Uterine bleeding
• Hematuria
2- Increased demands:
• Immaturity
• Growth
• Pregnancy
• EPO therapy
3-Malabsorption:
• Enteropathy
• Gastrectomy
4-Poor diet: Rare as the only cause (rule out other causes)
 Development of IDA

4 3 2 1
Iron def. Latent Pre-latent Normal
anemia

Low Low Low Normal Stores

Low Low Normal Normal MCV/MCH

Low Normal Normal Normal Hemoglobin

Signs of
anemia
 Signs and symptoms of IDA

b c
Beside symptoms and signs of anaemia +/- bleeding patients present with:
(a): Koilonychia (spoon-shaped nails)
(b): Angular stomatitis and/or glossitis
(c): Dysphagia due to pharyngeal web (Plummer-Vinson syndrome)
20
 Investigation

normal

Microcytic hypochromic anemia with:

• Anisocytosis( variation in size)
• Pokiliocytosis (variation in shape)
 Iron Studies

Normal IDA

TIBC*
high TIBC

• Serum Iron
• Serum ferritin • Low serum iron
• Transferrin • Low serum ferritin
saturation • Low transferrin
saturation

TIBC : total iron binding capacity of transferrin

 Iron Studies

Thalassemia Normal IDA

Low TIBC*

high TIBC

• High Serum Iron

• High Serum ferritin
• High Transferrin
• Low serum iron
saturation
• Low serum ferritin
• Low transferrin
saturation
 Investigation

BM Iron stain (Perl’s stain): The gold standard but invasive procedure

Normal IDA: reduced or absent iron stores

(hemosiderin)
 Treatment of IDA

• Treat the underlying cause

• Iron replacement therapy:
Oral :( Ferrous Sulphate OD for 6 months)
Intravenous:( Ferric sucrose OD for 6 months)

Hb should rise 2g/dL every 3 weeks

 PREVENTION OF IDA

• Dietary modification
Meat is better source than vegetables.

• Food fortification (with ferrous sulphate)

• GIT disturbances ,staining of teeth & metallic taste.

• Iron supplementation:
For high risk groups.
 Anemia of chronic disease

• Normochromic normocytic (usually) anemia caused by

decreased release of iron from iron stores due to raised
serum Hepcidin .
• Associated with
- Chronic infection including HIV, malaria
- Chronic inflammations
-Tissue necrosis
-Malignancy
 IL-6
Tuberculosis IL-1
SLE TNF
Carcinoma
Lymphoma
+ve

Hepcidin
- ve

no Iron for
erythropoeisis

BM macrophage
 Work-up and treatment

• Normocytic normochromic or mildly microcytic anaemia

• Low serum iron and TIBC
• Normal or high serum ferritin ( acute phase reactant)
• High haemosiderin in macrophages but low in normoblasts

Management:
Treat the underlying cause
Iron replacement +/- EPO 29