Diagnosis

How do you define Iron Deficiency Anaemia?

IDA occurs in 2-5% of adult men and postmenopausal women

in the developed world, and is a common cause of referral to
gastroenterologists (4-13% of referrals).
While menstrual blood loss is the most common cause of IDA
in premenopausal women, blood loss from the GI tract is the
most common cause in adult men and postmenopausal
women.
The World Health Organization defines anaemia as a
haemoglobin (Hb) concentration below 13 g/dl in men over 15
years of age, below 12 g/dl in non-pregnant women over 15
years of age, and below 11 g/dl in pregnant women.
The serum markers of iron deficiency include low ferritin, low
transferrin saturation, low iron, raised total iron-binding
capacity, raised red cell zinc protoporphyrin, and increased
serum transferrin receptor (sTfR). Serum ferritin is the most
powerful test for iron deficiency in the absence of
inflammation.
The cut-off concentration of ferritin that is diagnostic varies
between 12 and 15 mg/l.16 17 This only holds for patients
without coexistent inflammatory disease. Where there is
inflammatory disease, a concentration of 50 mg/l or even
more may still be consistent with iron deficiency.

Assessment
How should I assess a person with iron deficiency anaemia?
The assessment should aim to determine whether there is an
underlying cause of the iron deficiency anaemia, and whether the
person has any complications, through history, examination, and
appropriate investigations.
History
What history should I take at initial assessment?
Ask about:
Diet (to identify poor iron intake).
Drug history (for example the use of aspirin, nonsteroidal antiinflammatory drugs, selective serotonin reuptake inhibitors,
clopidogrel, or corticosteroids).
History of overt bleeding or blood donation.
Menstrual history (if appropriate).
History of recent illness which might suggest underlying
gastrointestinal bleeding.
Gastrointestinal symptoms (including altered bowel habit).

Weight loss.
Travel history (increased risk of hookworm in travellers to the
tropics).
Family history of:
Iron deficiency anaemia (which may indicate inherited
disorders of iron absorption).
Haematological disorders (for example thalassaemia).
Bleeding disorders and telangiectasia.
If the anaemia is severe, ask about specific cardiac symptoms
(for example angina, palpitations, and ankle swelling).

Examination
What should I look for on examination?

To determine whether there is an underlying cause for the

anaemia, and whether the person has developed
complications:
Examine the abdomen for abdominal masses, organomegaly,
lymphadenopathy, and other features of intra-abdominal
disease.
If there is a history of rectal bleeding and/or tenesmus,
perform a rectal examination.
Examine the cardiovascular system and chest for signs of
heart failure.
If heavy menstrual bleeding is thought to be the cause of iron
deficiency anaemia, see the CKS topic on Menorrhagia.

How does Iron Deficiency Anaemia present?

Symptoms
What are the symptoms?
Symptoms associated with iron deficiency anaemia will

depend on how quickly the anaemia develops.

o

People with chronic, slow blood loss may be able to

tolerate very low levels of haemoglobin with few symptoms.
Symptoms commonly include fatigue, dyspnoea, and

palpitations.
Less common symptoms include:

Headache.

Tinnitus.

Taste disturbance.

Pruritus.

Pica (abnormal dietary cravings, for example for ice or

clay).

Sore tongue.

Dysphagia (in association with oesophageal web which

occurs in Patterson-Brown-Kelly or Plummer-Vinson syndromes).
Impairment of body temperature regulation (in pregnant

women).
Serious symptoms such as angina, marked ankle oedema, or

dyspnoea at rest are unlikely at haemoglobin concentrations of

more than 7 g/100 mL unless there is additional heart or lung
pathology. Angina may occur if there is pre-existing coronary
artery disease.
Symptoms of iron deficiency may occur without anaemia.

These symptoms include fatigue, hair loss, lack of concentration,

and irritability.
Signs
What are the signs?
There may be no signs, even if the person has severe

anaemia.

Pallor may be observed even with mild anaemia.

Less commonly, the following signs may be observed:

o

Atrophic glossitis.

Angular cheilosis (ulceration of the corners of the

mouth).

Nail changes, such as longitudinal ridging and

koilonychia (spoon-shaped nails).

Tachycardia, murmurs, cardiac enlargement, and heart

failure may occur if anaemia is severe (haemoglobin less

than 8 g/100 mL).

Investigations
What investigations should I consider prior to treatment?
Confirm the diagnosis of iron deficiency anaemia, if this has
not already been done. Ideally, the likely cause should be
documented (for example menstruation or frequent blood
donation).

Screen all people with iron deficiency anaemia for coeliac

disease using coeliac serology (presence of anti-endomysial

antibody or tissue transglutaminase antibody). If positive,
refer for further investigations. See the CKS topic on Coeliac
disease.
It is usually unnecessary to further investigate the following

groups of people prior to treatment:

Otherwise healthy young people in whom the history clearly

suggests a cause (for example regular blood donors).

Menstruating young women with no history of gastrointestinal

symptoms or family history of colorectal cancer.

Pregnant women investigations (to determine an underlying
cause or the presence of complications) are not usually
needed if anaemia develops during pregnancy unless the
anaemia is severe, the history and examination suggest an
alternative cause of iron deficiency (for example inflammatory
bowel disease), or there is no response to iron
supplementation.

A full blood count is routinely done in pregnancy and may

show low levels of Hb, mean cell volume, mean cell Hb, and
mean cell Hb concentration; a blood film may confirm the
presence of microcytic hypochromic red cells and
characteristic 'pencil cells'; however:

o Hypochromic indices may also occur in

haemoglobinopathies and thalassaemia [Baker,
2000; Youart, 2006; Pavord et al, 2012].
o In pregnancy, a physiological reduction in Hb
concentration occurs, which does not represent
anaemia. There is an increase in red cell mass and
plasma volume; the plasma volume increases more than
the red cell mass, causing a relative Hb reduction in a
peripheral blood sample [Baker, 2000; Letsky, 2003].
o Normal pregnancy is also associated with a slight
increase in mean cell volume (by approximately
4 femtolitres) and for milder cases of iron deficiency, the
mean cell volume may not fall below the normal range
[Letsky, 2003; Pavord et al, 2012].

There is a lack of agreement on the Hb level for the diagnosis

of anaemia during pregnancy [Letsky, 2003]

Test the urine for blood.

Refer for upper and lower gastrointestinal (GI) investigations.

For information on when to refer for upper and lower GI

investigations, see Referral or seeking specialist advice.
Consider stool examination to detect parasites, if appropriate

from the person's travel history.

If there is a poor response to empirical iron treatment, or

recurrence of anaemia without an obvious cause, seek

specialist advice regarding further assessment and
investigation.
If the person has already had normal upper and lower

gastrointestinal investigations for iron deficiency anaemia and

the anaemia persists or recurs, consider testing for
Helicobacter pylori, and eradicate if present.
See the CKS topic on Menorrhagia for information on
appropriate investigations if a woman has heavy menstrual
bleeding.

The WHO defines anaemia as Hb level less than

11 g/100 mL throughout pregnancy (this is the most widely
used definition worldwide) [WHO et al, 2001].

A UK guideline on the management of iron deficiency in

pregnancy states that Hb level of 11 g/100 mL or more appears
adequate in the first trimester, and a level of 10.5 g/100 mL
appears adequate in the second and third trimesters [Pavord et
al, 2012].
If results show a low haemoglobin and low mean cell volume

(microcytic anaemia):
o

For a non-pregnant person, check the ferritin level

(see Interpreting ferritin levels in a non-pregnant person)

For a pregnant woman, consider checking ferritin

levels but be aware that results may be less reliable in
pregnancy (see Interpreting ferritin levels in pregnancy).

KEY POINT levels differ

If the diagnosis of iron deficiency anaemia is in doubt despite

serum ferritin results, diagnostic trials of iron treatment can be

considered in premenopausal women with a history of
menorrhagia, or pregnant women (if there is no suspicion of
Coeliac disease).
o

A diagnostic trial of iron treatment should not be

used for men and postmenopausal women as they are
more at risk of occult gastrointestinal bleeding and
malignancy.

It is less clear in which groups of people vitamin B12 and

folate levels should also be checked, and when this should be
done.

When should I refer or seek specialist advice?

For people of any age who present with:

Iron deficiency anaemia with dyspepsia refer urgently

(within 2 weeks) for endoscopy.

Iron deficiency anaemia without dyspepsia recognize

the possibility of gastrointestinal cancer and consider urgent

referral for further investigations.

In all cases, both upper and lower gastrointestinal

investigations are recommended, unless the upper
gastrointestinal endoscopy detects gastric cancer or coeliac
disease (in which case lower gastrointestinal investigations
are not necessary).
For men of any age with unexplained iron deficiency

anaemia and a haemoglobin level of 11 g/100 mL or below

refer urgently (within 2 weeks) for upper and lower
gastrointestinal investigations.
For women who are not menstruating, with

unexplained iron deficiency anaemia and a haemoglobin

level of 10 g/100 mL or below refer urgently (within 2
weeks) for upper and lower gastrointestinal investigations.
People with unexplained iron deficiency anaemia who

do not fulfil these criteria for urgent referral will still require
referral for upper and lower gastrointestinal investigation. The
urgency of this will require clinical judgement, based on the
haemoglobin level and clinical findings.
Other situations in which specialist expertise is

required include:
o

If coeliac serology is positive refer to

gastroenterology.

If the person has profound anaemia with signs of heart

failure admit to hospital.

If a woman with menorrhagia has iron deficiency

anaemia that has failed to respond to treatment refer to a

gynaecologist (urgency of referral should reflect clinical

judgement).
If a person is unable to tolerate, or is not responding to,

oral iron treatment seek specialist advice.

If a person who has initially responded to iron treatment

develops anaemia again without an obvious underlying cause

seek specialist advice regarding further assessment and
investigation.

Differential diagnosis
What else might it be?
The differential diagnosis of microcytic anaemia includes:

Thalassaemia.

Sideroblastic anaemias.

Anaemia of chronic disease.

Lead poisoning (rare in adults).

Thalassaemia and sideroblastic anaemia are both associated

with an accumulation of iron, so tests will show an increase in

serum iron and ferritin, and a low total iron-binding capacity.

For people with thalassaemia trait (alpha or beta), the mean

cell volume, mean cell haemoglobin, and mean cell haemoglobin
concentration are all reduced and are very low for the degree of
anaemia.

MANAGEMENT
Treating iron deficiency anaemia
How should I treat iron deficiency anaemia?

Address underlying causes as necessary (for example treat

menorrhagia or stop nonsteroidal anti-inflammatory drugs, if

possible).
Treat with oral ferrous sulphate 200 mg tablets two or three

times a day.
o

If ferrous sulphate is not tolerated, consider oral ferrous

fumarate tablets or ferrous gluconate tablets.

Do not wait for investigations to be carried out before

prescribing iron supplements.
If dietary deficiency of iron is thought to be a contributory

cause of iron deficiency anaemia, advise the person to maintain

an adequate balanced intake of iron-rich foods (for example dark
green vegetables, iron-fortified bread, meat, apricots, prunes, and
raisins) and consider referral to a Idietitian.
Monitor the person to ensure that there is an adequate

response to iron treatment.

Iron supplements
The aim of treatment is to restore haemoglobin levels and red

cell indices to normal, and to replenish iron stores [Goddard et al,

2011].
Dose-related adverse effects from taking an iron supplement

are commonly experienced. It may be good practice to

recommend ferrous sulphate 200 mg (65 mg elemental iron
content) twice a day until the clinical response is assessed after
24 weeks, and thereafter:

If well tolerated, increase to three times a day.

If poorly tolerated, reduce to once a day.

Alternatively, if ferrous sulphate is not tolerated then the

person may prefer taking a different iron preparation such as

ferrous gluconate [BNF 64, 2012].

Ferrous gluconate 300 mg tablets may be better

tolerated than ferrous sulphate as there is less elemental iron

content per tablet than ferrous sulphate.
Ferrous fumarate tablets contain more elemental iron

per tablet than ferrous sulphate and is therefore likely to be no

better tolerated.
See Iron content in different iron salts.

Iron absorption may be [Heath and Fairweather-Tait,

2002; Killip et al, 2007]:

Increased if a person has a high intake of fish, or red or

white meat.
Reduced if a person has a high intake of phytate (for

example from wholegrain cereals), polyphenols (for example

from tea and coffee), calcium (for example from dairy
products), or if the person is taking medication that raises the
gastric pH (for example antacids and proton pump inhibitors).
Monitoring during treatment
What monitoring is recommended for someone being
treated for iron deficiency anaemia?
Recheck haemoglobin levels (full blood count) after 24 weeks

to assess the person's response to iron treatment. The

haemoglobin concentration should rise by about 2 g/100 mL over
34 weeks.
If there is a lack of response, see Inadequate benefit

from initial iron treatment.

If there is a response, check the full blood count at 2

4 months to ensure that the haemoglobin level has returned to

normal.

Once haemoglobin concentration and red cell indices are

normal:

Continue iron treatment for 3 months to aid

replenishment of iron stores, and then stop.

Then monitor the person's full blood count every

3 months for 1 year.

Recheck after a further year, and again if symptoms of

anaemia develop subsequently.

If haemoglobin or red cell indices drop below normal,

give additional iron.

Consider an ongoing prophylactic dose in people who are at

particular risk of iron deficiency anaemia.