Iron deficiency anaemia (IDA) and other

hypochromic microcytic anaemias

Dr Chandima Kulathilake
Senior Lecturer/Consultant Haematologist
Dept of Pathology

Contents

 Iron distribution, absorption & transport

 Causes of IDA
 Diagnosis –clinical & laboratory
 Management of IDA
 D/D IDA(other hypochromic microcytic anaemias)

Iron deficiency is the most common cause of anaemia in every country of the world. This is
because the body has a limited ability to absorb iron in the duodenum.

Distribution of body iron

Human body has 3-4g of iron which is distributed as follows:

1. 65% - Haemoglobin
Iron is attached to the protoporphyrin ring and makes the haem component.
2. 30% - ferritin and haemosiderin
These are body iron stores which are in ferric form in macrophages mainly in bone
marrow, liver and spleen.

3. 3.5% - Myoglobin
Iron is also present in muscle as myoglobin
4. 0.5% - Haem enzymes
Most cells in the body have iron containing enzymes. eg.Cytochromes
5. 0.1% - transferrin bound iron

This is the carrier protein of iron. It delivers iron to tissues with transferrin receptors such as
erytrhoblasts (red cell precursors)in bone marrow.

Iron absorption
Iron is absorbed in the duodenum & upper jejunum. The average western diet contains about 10-
15mg of iron from which only 5-10 % (1-1.5mg) is usually absorbed. This amount is equal to the
usual daily loss of iron.
In a adult male the loss is usually 0.5-1mg and in a menstruating female it is 1-2mg per day.
The absorption may be increased to 20-30% in iron deficiency and pregnancy.
Iron absorption is increased by - Fe2+ form, reducing substances eg Acid & vit C, Haem iron(in
red meat and fish)
reduced by – Phytates,Oxalates,Fe3+ ,Tea, alkali(antacids), infection

Causes of Iron deficiency

1. Chronic blood loss-Mainly gastrointestinal & uterine

Eg.peptic ulcer,oesophageal varices,carcinoma of stomach/ colon.

This is the leading cause of IDA esp in developed countries. IDA may be the first presentation in
an elderly male with an underlying hidden colonic carcinoma.

2. Inadequate intake - poor diet

This is the common cause in developing countries
3. Malabsorption - Gastrectomy, Coeliac disease
Tropical sprue, Worm infestation
4. Increased demand - Prematurity, Growth, pregnancy

Clinical features

Patients present with general symptoms and signs of anaemia.eg SOB on exertion
In addition, following features may be seen.
 - painless glossitis -red, smooth tongue,but not sore or painful as in megaloblastic
anaemia
- angular stomatitis –fissuring of corners of mouth
- koilonychia –brittle, spoon shaped nails with ridges
- pica –abnormal dietary cravings eg.eating raw rice
- Poor cognitive function in children

Haematological findings

 FBC/Red cell indices

Haemoglobin less than that is appropriate for age and sex of the individual
As, this is a hypochromic microcytic anaemia, the MCV and MCH are invariably low.
MCH < 27 pg (NR 27-32)
MCV < 80 fL (NR 80-95)

In addition,following 02 indices also show changes,low MCHC and high RDW.

MCHC < 30 g/dL (NR-30-35)

RDW > 14% (Normal <14%)
(As red cells show size variation in IDA,RDW increases.)

 Blood film- Hypochromic microcytic cells

Pencil shaped poikilocytes
(poikilocyte is a cell with abnormal shape)

 Reticulocyte count is low in relation to the degree of anaemia. As this is a deficiency

state, marrow cannot produce new cells.
 Platelet count is moderately increased esp. when there is a chronic blood loss (reactive
response by bone marrow)

 Serum ferritin-low in IDA

A small fraction of body ferritin (iron stores) circulates in serum and this concentration correlates
with the iron stores. So, when iron stores are deficient in IDA, serum ferritin also goes down.
Serum ferritin is raised as an acute phase reactant in acute inflammatory conditions. Therefore,
testing serum ferritin is better avoided during an acute illness even though IDA is suspected, as
you cannot interpret it correctly.

 Serum iron studies

1.Total Iron Binding Capacity(TIBC)

This is the binding capacity of transferrin with Fe. We do not measure the amount of transferrin
directly in a person, instead we indirectly measure the binding capacity. In IDA as a measure of
binding more and more available little amount of iron, transferrin synthesis by the liver goes up.
So, TIBC is increased than in a normal person

2. Serum iron
This is the amount of iron bound to transferrin. This is low in IDA

3.Transferrin saturation%
Serum iron is expressed as a percentage fraction of transferrin. This is low in IDA

So, the report of iron status in a patient with IDA is as follows:

 TIBC(Total Iron Binding Capacity)

 Transferrin saturation(%)

 Serum iron (Transferrin bound Fe)

 TIBC

19

A Normal

B Iron deficiency

C Anaemia of chronic

ds

D Iron overload

TIBC
Serum
iron
  Bone marrow iron stores– depleted in IDA
Bone marrow iron can be visualized by staining a bone marrow smear with perls stain.
(haemosiderin deposits appear blue).
Bone marrow examination to assess iron stores is not essential for diagnosis except
in complicated cases.

 Serum transferrin receptor (sTfR )assay- Inreased.

Transferrin receptors are shed from cells into plasma and this can be measured. In IDA
these receptors are increased in cells to grab more iron from transferrin so that shedded
amount will be increased in the serum. This is a very sensitive indicator of IDA.
(Not available in SL)

Once iron deficiency is confirmed underlying cause should be investigated.

 Investigation of a cause
1. Dietary history
2. Source of bleeding
Stool AOC ,occult blood
Endoscopy, Colonoscopy
Ultrasound scan

Management
1. Correction of underlying cause
2. Fe replacement
Iron is given to correct the anaemia and replenish iron stores
 Oral iron peparations
Best preparation is FeSO4 which contains elemental iron 67mg in each 200mg tab.
Usually elemental iron 100-200mg/daily is given in treatment. (1tab bd or tds)
Usu.06 months Rx needed to correct anaemia and replenish body stores
This is best given on an empty stomach, but if side effects occur (nausea,epigastric
pain,diarrhoea)it may be given with food.
Lower iron preparations such as Fe fumarate & Fe gluconate may also be used when side
effects cannot be tolerated with ferrous sulphate.
Slow release iron preparations should not be used, as iron is released beyond duodenum
and will not be absorped much.

 Parenteral preparations
Iron- Sucrose preparations have less side effects.
They replace iron stores reliably and faster, but no rapid haematological response occurs
than oral.
Risk of anaphylaxis is present.
 Parenteral iron is indicated only in special situations
Malabsorption
With erythropoietin Rx
late pregnancy (to replenish iron stores rapidly)
Chronic haemodialysis
When oral iron is impractical

 Monitoring Rx response
Retic count – Starts to rise in 3rd day of treatment. Peak in 7-10 days
Hb rise by 2g/dL every 3 weeks

 Failure to respond to oral Fe Rx

• Poor compliance
• Continuing blood loss –menorrhagia or GIT loss
• Wrong diagnosis –another type of hypochromic microcytic anaemia such as thalassaemia
trait
• Malabsorption
• Underlying malignancy/Chronic inflammatory ds where the cause of anaemia is
Anaemia of chronic disorder

D/D There are 04 other types of hypochromic microcytic anaemias

• Anaemia of Chronic Disorder (ACD)

This occurs in a variety of chronic inflammatory (TB, Rheumatoid arthritis,SLE) and
malignant diseases. This is an important category in adult practice. Anaemia is hypochromic
microcytic or may be normochromic normocytic anaemia

Pathogenesis
Due to inflammation, cytokines such as interleukin-1 and 6,TNF are increased in blood.
They induce synthesis of hepcidin from liver.Hepcidin is an iron regulatory hormone and an
acute phase protein.
Hepcidin causes,
 Decreased release of iron from macrophages(iron stores) & decreased absorption
from gut.
In addition due to cytokines, there is an inadequate erythropoietin response to anaemia and
reduced red cell life span in ACD.

Iron studies show ,

a)normal or raised s.ferritin (as marrow iron stores are increased)
b) low serum iron
 c) low TIBC- in any chronic inflammatory condition protein synthesis is
reduced,therefore transferrin level goes down.
d) % saturation –low normal value

Management
ACD does not respond to iron Rx. So, iron should not be given for months and months.This
applies to a patient with an acute illness as well.Same pathogenesis will operate in an acute
illness and iron will not be absorped.
Rx of the underlying ds will correct anaemia. Erythropoietin treatment will improve anaemia in
some cases.

 Thalassaemia trait (Thalassaemia carrier)

Usually they have mild anaemia with low MCV & MCH. This an important category in
paediatric practice, when you handle a child with hypochromic microcytic anaemia.

Unlike in iron deficiency,in FBC they have normal MCHC &RDW, but raised RBC count.
( RBC count >5.5 x1012/L)

Iron studies are normal

Diagnosis is confirmed by High Performance Liquid Chromatography(HPLC) or Hb
electrophoresis, where there is in elevated Hb A2 fraction (3.5-7%) in beta thalassaemia trait.
Genetic studies are needed in alfa thalassaemia trait

 Sideroblastic anaemia
There is a defect in haem synthesis, and erythroblasts with iron granules arranged in a ring
appear in the marrow.They are known as ring sideroblasts.

Serum iron is raised, TIBC is normal,and serum ferritin is increased.

 Lead Poisoning

Lead inhibits both haem and globin synthesis and cause hypochromic microcytic anaemia.
As it also interferes with RNA breakdown,denatured RNA accumulates in RBC giving the
appearance of basophilic stippling.
 Basophilic stippling

Laboratory Iron Anaemia Thal Sideroblastic

Measure deficiency of trait anaemia
chronic
disorder
Serum iron Reduced Reduced Normal High

TIBC increased reduced Normal Normal

Serum Reduced Normal/ Normal High

ferritin Raised
Bone Absent present present present
marrow
iron
sTfR Increased Normal Variable Normal
/low
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