IRON DEFICIENCY ANEMIA

Manish Jain
Objectives
• Understand the basic physiology of iron absorption,
transport and storage

• Understand the causes of iron deficiency and the

compensatory responses

• Understand modalities of treatment of iron deficiency

and anemia
 Red Blood Cell Production
• RBC production (erythropoiesis) takes place in the bone
marrow under the control of the hormone erythropoietin.

• Erythroblasts require
folate and vitamin B12
for proliferation during
their differentiation.

• Vitamin C stimulates
the release of iron
from storage in ferritin
deposits
 Requirements for Red Blood Cell
Production
• Erythropoeitin
• Proteins, required for globin synthesis
• Iron
• Vitamin B12 and folic acid
• Vitamin B6
• Vitamin C
 Iron Distribution
Mostly within the cardiovascular system, liver and blood:

Red blood cells 1.8 g

RES macrophages 0.6 g
Liver 1.0 g
Bone marrow 0.3 g
Muscles (myoglobin) 0.3 g
Other tissues 0.1 g
Bound to transport protein
Transferrin 0.003 g
 The Normal Hemoglobin Structure

•Consists of four protein

subunits:
• Two subunits of beta-globin
• Two subunits of alpha-globin.

•Each of the four protein

subunits carries an iron-
containing molecule called
heme.
 The Normal Hemoglobin Structure

•Heme molecules are

necessary for red blood cells
to pick up oxygen in the lungs
and deliver it to cells
throughout the body

•The HBB gene, located on

chromosome 11, provides
instructions for making a
protein called beta-globin.
 Hemoglobin in RBC
Heme is a
porphyrin
ring containing
an iron atom

Each Hb
molecule
can bind 4
oxygen
molecules
at heme site
About 70 percent of our body's iron is found in the red blood cells called hemoglobin
Schechter BLOOD, 15 NOVEMBER 2008
VOLUME 112, NUMBER 10
 Iron Requirements

• Most dietary iron is nonheme form, <5% bioavailability

• < 10% dietary iron is heme form, >25% bioavailability

Blood loss at delivery not included.
 Iron source
• Food sources supply: 10 -
25 mg / day

• Richest sources of heme

iron - calf meat, seafood.

• Dietary sources of nonheme

iron - nuts, beans,
vegetables, and grains.

• Absorbed in the brush

border of the upper small
intestine
Iron Absorption
Enhanced by
• Vitamin C
• Lactose
• gastric acid

Inhibited by
• Tannins
• Polyphenols
• systemic inflammation
 Iron Absorption
• Once the food is consumed and digested, dietary iron is
mainly absorbed in the duodenum and proximal jejunum.

• Heam iron is
absorbed
more
efficiently
than non-
haem iron-
Fe3+ to Fe2
 Iron Absorption
• Iron it is either stored in the enterocyte as ferritin

• Exported from the enterocyte via ferroportin transporter as

ferrous iron which is immediately oxidized to Fe3+

• Fe3+ is picked up
by transferrin to be
transported to cells
expressing
transferrin
receptors
Rate of Iron Absorption
Depends on

• Total iron stores

• The extent to which the bone marrow is producing
new red blood cells
• The concentration of hemoglobin in the blood,
• The oxygen content of the blood.
 The iron cycle
Most cycling iron comes
from the spleen, where
RBCs are destroyed by
splenic macrophages;

The iron is recycled to the

bone marrow via
transferrin
Iron Losses
• Iron is closely conserved in humans
<0.05% of iron is lost per day normally

1. Very small amounts in urine, bile and sweat

2. Cells shed from skin, intestinal and urinary tracts

3. Menstrual blood loss

4. Pregnancy and lactation

Iron Losses
Other causes of iron loss
• Blood donation
• Use of anti-inflammatory drugs that cause bleeding
from the gastric mucosa
• GI disease with associated bleeding

• Humans have NO other physiologic means to excrete

excess iron
 Pathogenesis of Iron Deficiency
• Inadequate iron absorption
• Diet low in heme iron

• Poor bioavailability (Antacid therapy or high gastric pH)

• Gastrointestinal disease (IBD) or surgery

• Excessive cow’s milk intake in infants (bovine milk has

a higher concentration of calcium, which competes with
iron for absorption)

• Excess dietary tannin or phytates

Pathogenesis of Iron Deficiency
 Pathogenesis of Iron Deficiency
• Blood loss
• Blood in the feces (Ulcer, tumor, haemorrhoids, chronic
infection),
• Traumatic or surgical losses

• Failure to meet increased requirements

• Rapid growth in infancy and adolescence
• Menstruation, pregnancy

Infestation with parasitic worms

Hookworms, Whipworms - suck 0.03- 0.2 ml of blood per
worm /day)
Risk factors for IDA

• Demographic – Elderly, Teenager, Female

• Dietary – low Iron, low Vit C, excess phytate, tea coffee

• Social and physical – poverty, alcohol abuse, GIT ds

 Symptoms of iron deficiency with
or without anaemia
• Shortness of breath
• Fatigue
• Reduced physical performance
• Increased susceptibility for
infections
• Pale skin colour, hair loss and
brittle nails
 Symptoms of iron deficiency with
or without anaemia
• Iron-deficiency anemia can
cause:
• Brittle nails

• cracks in the sides of the

mouth
Iron Deficiency is the most common cause of
Anemia

• What is Anemia?

• Reduction of the red blood cell (RBC) volume or

hemoglobin concentration below reference level
for the age and sex of the individual
 Prevalence of iron deficiency Anemia

Countries Industrialised (%) Developing (%)

Children (0-4 years) 20.1 39.0
Children (5-14 years) 5.9 48.1
Pregnant women 22.7 52.0
Women in
10.3 42.3
reproductive age
Men (15-59 years) 4.3 30.0
Seniors 12.0 45.2
Features of Iron Deficiency Anemia
• Depends on the degree and the rate of
development of anemia
• Symptoms common to all anemias:

• Fatigability, weakness, dizziness, irritability

Tests for Iron Deficiency
• Red cell indices- MCV (Mean corpuscular volume-
measurement of the average size of RBC) and MCH
(mean corpuscular hemoglobin, amount of hemoglobin
per red blood cell)

• Serum ferritin
• Serum iron/ transferrin- iron saturation
• Bone marrow iron stain (Prussian blue)
Tests for Iron Deficiency
• Prussian blue
• Potassium ferrocyanide in
the staining solution
combines with the ferric iron
forming the Prussian blue
pigment
 Iron replacement strategies
• Dietary iron
• Oral iron- ferrous salts, 4–6mg/kg of elemental iron

Most patients are

treated initially with
oral iron unless
there is an
absorptive problem
 Iron replacement strategies
• FeSo4 BID

• TID is very constipating and causes gastric distress;

commonest cause for noncompliance
Iron replacement strategies

• Dietary iron+ Oral iron

• Parenteral iron- I.V. iron is no longer
‘dangerous. The newer formulations such as
iron sucrose, LMW iron dextran and ferric
gluconate have minimal risks of infusion
reactions
• Blood transfusion- In very severe cases
Oral iron therapy
• Advantages
: cheap
: easy to administer

• Disadvantages
:poorly absorbed (max 5-10 mg/day)
:GI side-effects common
:compliance often poor
:absorption limited if ferritin elevated
:absorption reduced in inflammation
 Limitations of oral iron therapies

May be • Accelerated erythropoiesis can increase

inadequate demand for iron beyond the amount supplied
during ESA orally
therapy
• Can affect over 50% of patients
Gastrointestinal • Can adversely affect nutritional intake
adverse events • Improved if iron tablets are taken with food,
but this decreases absorption
 Limitations of oral iron therapies
• Pill burden: usually 2 or 3 tablets per day
Compliance
• Gastrointestinal intolerance
• High oral iron doses can saturate the iron
Oxidative
transport system if the iron is rapidly
stress
released, resulting in oxidative stress
Response to oral Iron Therapy
• Increased Hb and Hct 14 - 21 d.

• Normal Hb and Hct 2 months

• Normal iron stores 4 - 5 months

 Limitations of oral iron therapies
Iron Poisoning.
• Large amounts of ferrous salts are toxic, but fatalities
are rare in adults. Most deaths occur in children,
particularly between the ages of 12 and 24 months.

• As little as 1–2 g of iron may cause death, but 2–10 g

usually is ingested in fatal cases

• All iron preparations should be kept in childproof

bottles.
 Limitations of oral iron therapies
• Iron Poisoning.
 Indications for iv iron
• Indicated for treatment of iron deficiency when oral iron
preparations are ineffective or cannot be used.

• Failure of oral iron due to g.i intolerance

• Failure of oral iron due to absorption issues
H pylori infection, autoimmune gastritis, gastric bypass
surgery, inflammatory bowel disease
• Heavy ongoing menstrual blood losses
Advantages for iv iron
• Comparative clinical trials show a faster and
more prolonged response with IV iron than with
oral iron.

• IV iron is more effective, better tolerated and

improves quality of life to a greater extent than
oral iron.

• Concerns regarding allergic reactions.

Parenteral iron
• HMW Iron dextran (not routinely used anymore due to a
much poorer safety profile in comparison to newer iron
preparations)
• Iron sucrose, LMW Iron dextran
• Ferric carboxymaltose, Ferric Gluconate, Ferumoxytol
 Blood Transfusion
Guidelines for Clinical Use of Red Cell Transfusions

• INDICATED where Hb level < 7g/dl

• NOT INDICATED where Hb level > 10g/dl

• UNCLEAR where Hb level is 7-10 g/dl

– Symptomatic
Blood transfusion
• Expensive
• Supply limitations
• Risks unique to transfusion
 Risks associated with transfusion
Category Risk per components
issued
Total risk of death 1 in 125,000
Total risk of major morbidity 1 in 19,157
Risk of death from TACO 1 in 227,273
Risk of major morbidity from TACO 1 in 81,3000

Transfusion-associated circulatory overload (TACO) is a common transfusion reaction in

which pulmonary edema develops primarily due to volume excess or circulatory overload
 Risks associated with transfusion

Category Risk of infected

donation entering
blood supply
HBV (Hepatitis B Virus) 1 in 1.3 million
HCV (Hepatitis C Virus) 1 in 28.6 million
HIV (Human Immunodeficiency 1 in 7.1 million
Virus)
Summary of treatment options
In Conclusion….
• IDA is a highly prevalent, but easily treatable condition
• Oral iron therapies are mostly equivalent in efficacy
• Infusion reaction rates are very low in iv iron products
other than HMW dextran
• Costs and indication for therapy are important to help
decide the best iv iron replacement product for a
patient.
THANK YOU!!