Case study 66 report:

Iron-deficiency
anaemia

January 2011

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 Inside
Case study 66: Iron-deficiency anaemia

Scenario and questions page 3

Summary of results page 4

Results in detail

Additional questions to aid diagnosis page 6

Investigations for confirming iron-deficiency anaemia page 7

Drug therapy for iron-deficiency anaemia page 8

Maximising oral iron absorption page 10

Indications for parenteral iron therapy page 11

Commentaries

Emeritus Professor Jack Metz page 12

Dr Pamela Burgar page 14

References page 16

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2
Case study 66
Iron-deficiency anaemia
Scenario
Mariah is a 17-year-old student who has recently migrated to Australia from Malta with her parents.
She comes to you complaining of general fatigue and occasional dizziness.
Mariah has no significant past medical history and is not on any regular medicines. She does not
drink alcohol or smoke. Her parents are both healthy.
On examination, she has strong peripheral pulses, and her cardiovascular system examination is
2
normal. BP is 115/75 mmHg, pulse 90 / minute, and BMI 19.5 kg/m . Mariah has pale skin,
conjunctiva and nail beds. Given her clinical symptoms, age and the findings on physical
examination, you suspect that Mariah may have iron deficiency anaemia.

1. To assist you in establishing a diagnosis of iron-deficiency anaemia, what additional

questions would you ask Mariah?
_____________________________________________________________________________________

2 a) Would you recommend any investigations to assist you in confirming Mariah’s iron-
deficiency anaemia?
yes (please specify) _________________________________________________________________
no, why not? _____________________________________________________________________

b) The most reliable marker of early iron deficiency is: _____________________________________

3 a) Would you recommend drug therapy for Mariah?

yes no

Why/why not? _______________________________________________________________________

b) If yes, specify
Medication Dose Frequency Durationi
____________________________ ___________________ __________________ ______________

4. Regardless of your answer in Q3, if Mariah were to be prescribed oral iron, list 2 strategies or
tips you would recommend for Mariah to maximise iron absorption.
_______________________________________________________________________________________

5. When is parenteral iron therapy indicated for iron-deficiency anaemia?

i) ___________________________________________________________________________________
ii) ____________________________________________________________________________________
iii) ____________________________________________________________________________________

3
Summary of results
At the time of publication, 718 responses had been received from doctors, and 200 of these have been
compiled for feedback.

Case synopsis

Mariah is a 17-year-old student who has recently migrated to Australia from Malta with her parents.
She comes to you complaining of general fatigue and occasional dizziness
Mariah has no significant past medical history and is not on any regular medicines. She does not
drink alcohol or smoke. Her parents are both healthy.
(See page 3 for more details).

Questions to aid in diagnosis of iron-deficiency anaemia

• Two most common questions respondents would ask Mariah to assist in establishing diagnosis of iron-
deficiency anaemia were about her menstrual history (32.3%) and her diet (31.3%)
• Less frequently asked questions were about Mariah’s family history (13.3%), GIT problems (10.5%)
and blood loss (10.5%).
• Some respondents would ask whether Mariah is pregnant, has infection, is depressed, has
haemorrhoids or recently donated blood.

Investigations to confirm diagnosis

• Investigations that respondents would recommend for confirming a diagnosis of iron-deficiency
anaemia varied. The most often mentioned were:
— full blood count (38.6(%)
— iron studies (35.7%).
• Other investigations mentioned by respondents were:
— haemoglobin H inclusion (8%), serum ferritin (6.3%) and vit B12/folate level (4.9%).
• Small number of respondents would recommend screening for coeliac disease (1.9%), and check
trasferrin saturation (1.5%) and occult blood (1.1%).

The most reliable marker of early iron deficiency

• Almost all respondents (94.1%) consider ferritin level as the most reliable marker of early iron
deficiency.
• Other tests chosen by small number of participants were
— transferrin saturation (1.5%)
— MCHC (1%)
— FBC (1%).

4
Drug therapy for iron-deficiency anaemia
• 82.3% of respondents would recommend drug therapy for Mariah.
• Reasons for recommending drug therapy included:
— if test results confirmed diagnosis of iron-deficiency anaemia (43.7%)
— Mariah’s symptoms (19.8%)
— for faster improvement ((6.6%)
— to replenish irons stores ((6.0%)
— drug therapy is the first-line treatment for iron-deficiency anaemia (1.2%).
• Reasons for not recommending drug therapy included:
— Diagnosis is not established (8.4%)
— No test results available (7.2%).
• Ferrograd C (41.7%) was the preferred choice of drug for Mariah.
• Most respondents (89.1%) would recommend once-daily frequency of taking medicine.
• The most commonly recommended dose of all medicines mentioned by 61.5% of respondents was
1 tablet.

Maximising oral iron absorption

• To maximise iron absorption, 36% of respondents recommended taking medicine on an empty
stomach, taking it with food (1%), avoiding tea, coffee or milk (21.5%) and taking it with vitamin C
(16.8%).
• Other recommendations were:
— lower dose of medication or take two divided doses (13%)
— take medicine with orange juice (5.7%)
— modify diet (did not specify) (2.8%)
— do not take with other medications (2.1%).

Parenteral iron therapy

• Adverse effects (29.8%) and GIT problems (23.3%) were the most common indications for parenteral
iron therapy suggested by participants.
• Other indications for parenteral iron therapy were high iron need and poor adherence to oral therapy
(14.6% and 13.1% of respondents, respectively).
• Failure of other therapy (9.9%), severe anaemia (6%) and other (3.3%) were also mentioned as
indications for parenteral iron therapy.

5
Results in detail
Additional questions to aid diagnosis
Respondents were asked to list additional questions they would ask Mariah to establish a diagnosis of
iron-deficiency anaemia. Table 1 summarises the responses.

Table 1: Additional questions

% of respondents
Questions (n = 200)*
Menstrual history 32.3
Diet 31.3
Family history 13.3
GIT problems 10.5
Blood loss 7.1
Pregnancy 2.0
Other medications 2.0
Other 1.6
* Respondents may have more than one response

Practice points
• Iron-deficiency anaemia may be due to physiological demands (growing children, pregnant women);
however, the underlying causes should be sought.
• The common causes of iron-deficiency anaemia include:3,6
— blood loss such as gastrointestinal in postmenopausal women and men, menstrual in
premenopausal women
— iron-deficiency anaemia due to malabsorption of iron may be caused by impaired gastric acid
secretion (including use of PPI) and intestinal problems (eg coeliac disease)
— iron deficiency anaemia may be caused by inadequate dietary iron intake (eg vegetarians) or
increased iron demand (eg pregnancy)
— other causes of iron deficiency anaemia that should be considered are: inflammation, thalassaemia,
blood donation.
• In establishing a diagnosis of iron-deficiency anaemia, a history of any of the following can be helpful5:
— the patient’s symptoms, including extreme fatigue, weakness, shortness of breath, headache,
dizziness or light-headedness, cold hands and feet, inflammation or soreness of tongue, brittle nails,
arrhythmia, unusual cravings for non-nutritive substances, such as ice, dirt or pure starch
— Diet, family history, heavy menstrual periods in premenopausal women, pregnancy, blood in urine
or stools, history of ulcer, uterine fibroid, colon polyp, colorectal cancer, recent blood donation
more than once
— the patient’s medications, including NSAIDs, PPIs, vitamins, supplements.

6
Investigations for confirming iron-deficiency anaemia
Respondents were asked if they would recommend any investigations to confirm a diagnosis of iron-
deficiency anaemia for Mariah. Table 2 summarises the responses.

Table 2: Investigations to assist in confirming iron-deficiency anaemia

% of respondents
Investigations (n = 200)*
FBC 38.6
Iron studies 35.7
HbH 8.0
Serum ferritin 6.3
B12/Folate 4.9
Coeliac screen 1.9
Transferrin saturation 1.5
Occult blood 1.3
ESR 1.1
Other 0.8
* Respondents may have more than one response

Respondents were asked to identify the most reliable marker for early iron-deficiency anaemia. Table 3
summarises the responses.

Table 3: The most reliable marker of early iron-deficiency anaemia

% of respondents
Investigations (n = 200)
Ferritin 94.1
Transferrin saturation 1.5
MCHC 1.0
FBC 0.5
Other* 2.5

* Other included iron studies, MCV, HbH

Practice points
• Serum ferritin — not serum iron — is the most sensitive marker of early iron deficiency and is the
preferred initial diagnostic test.1,2, 7,9,10 Serum ferritin level correlates with total body iron stores and a
low level can be seen before serum iron is affected.9,10
• Assess the state of the iron stores by considering together the serum ferritin, iron and transferrin
(indirectly measured by total iron binding capacity).8
• Iron studies are useful for investigating blood loss, anaemia or fatigue, dietary assessments and
monitoring the efficacy of iron therapy.1
• Other than iron deficiency, other conditions that should be considered in the differential diagnosis of a
hypochromic microcytic anaemia include the thalassemias, anaemia in chronic inflammation and
sideroblastic anaemia.8

7
Drug therapy for iron-deficiency anaemia
82.3% of respondents would recommend drug therapy for Mariah, whereas 17.7% would not. Table 4
summarises the reasons.

Table 4: Reasons for recommending or not recommending drug therapy

% of respondents
Reasons for recommending drug therapy (n = 200)*
If results show iron deficiency 43.7
Symptomatic 19.8
For faster improvement 6.6
To replenish iron stores 6.0
First line 1.2
Other 0.02

% of respondents
Reasons for not recommending drug therapy (n = 200)
Diagnosis not established 8.4
No test results 7.2

* Respondents may have more than one response

Respondents were asked to specify the medication, and its dose, frequency and duration if they would
recommend iron therapy to Mariah. Tables 5 and 6 summarises the responses.

Table 5: Recommended medicines

Medication % of respondents
(n = 200)
Ferrograd C 41.7
Ferro-Gradumet 25.2
Ferro-F 16.0
Iron supplements 6.7
Fefol 4.9
Ferrous sulphate 3.7
FGF 1.8

Table 6: Frequency of medication

Frequency % of respondents
(n = 200)
Daily 89.1
Twice daily 10.9

8
The recommended dosage of medicines varied. It ranged from half to two tablets or 100–500 mg.

Table 7: Recommended duration of therapy

Duration of therapy % of respondents
(n = 200)
2-4 months 59.5
3-6 months 19.0
1-2 months 9.2
>6 months 8.5
2-4 weeks 2.0
Other 2.0

Practice points
• The goal of therapy in iron-deficiency anaemia is not only to treat the anaemia, but also to provide
stores of at least 0.5–1.0 g of iron.8 However, guidelines vary in their recommendations for the
duration of iron therapy after the anaemia has been corrected: 3–4 months3,5,6, 4–6 months4 or
6–12 months.8
• Oral iron therapy is first line for most cases of iron-deficiency anaemia (pregnant women, growing
children and adolescents, patients with infrequent episodes of bleeding, and those with inadequate
dietary intake of iron). It is safer, more convenient and less expensive when compared with parenteral
iron therapy.7
• There are more than 100 preparations containing oral iron available over-the-counter in Australia but
only few contain enough elemental iron to treat iron-deficiency anaemia.5
• To reduce dose-related gastrointestinal adverse effects (abdominal pain, nausea, vomiting,
constipation and diarrhoea) and black discolouration of faeces, recommendations are to start oral iron
therapy at a low dose and gradually increase, or give in smaller doses more often. This strategy may
lead to better adherence to oral iron therapy.5,11
• Controlled-release oral iron preparations have fewer gastrointestinal adverse effects, but may also have
lower bioavailability.14,15
• Haemoglobin is expected to rise 1–2 g/L daily or 20 g/L over 3–4 weeks on oral iron therapy.5
• Haemoglobin should be monitored for response to oral iron therapy (after 2–4 week initially, then
after 2–4 months).4 The absence of a response may be due to poor absorption, noncompliance (which
is common), or coexisting problems.5,8
• Increasing dietary intake alone is inadequate to treat iron deficiency anaemia; however, dietary advice
should be part of the treatment plan.
• Absorption of haem iron (animal sources) is better than non-haem iron (cereal and vegetable sources).
Vitamin C enhances absorption of non-haem iron whereas calcium and products containing tannin
inhibit.14

9
Maximising oral iron absorption
Respondents were asked to list two strategies they would recommend for Mariah to maximise oral iron
absorption. Table 8 summarises the responses.

Table 8: Strategies to maximise oral iron absorption

% of respondents*
Strategies (n = 200)
Take on empty stomach 36.0
Do not take with tea, coffee, milk 21.5
Take with vitamin C 16.8
Take lower doses more often 13.0
Take with orange juice 5.7
Diet modification 2.8
Do not take with other medications 2.1
Take with food 1.0
Other 1.0

* Respondents may have more than one response

Practice points
• Patients need to be advised to avoid taking iron supplements with tea or coffee, as tannins can form
insoluble complexes with iron, reducing its absorption.12,13
• Oral iron preparations should be taken on an empty stomach, as food may inhibit iron absorption.5,8
However, if oral iron causes gastric upset, it can be taken with or shortly after food.5
• Iron can form poorly soluble complexes with other drugs, reducing absorption of both iron and the
other drugs (e.g. antacids, calcium, oral bisphosphonates, thyroid hormones).5,13

10
Indications for parenteral iron therapy
Respondents were asked to list reasons for recommending parenteral iron therapy in iron-deficiency
anaemia. Table 9 summarises the responses.

Table 9: Indications of parenteral iron therapy

% of respondents
Indications (n = 200)
Adverse effects of oral iron therapy 29.8
GIT problems 23.3
High iron need 14.6
Poor adherence 13.1
Other therapy failed 9.9
Severe anaemia 6.0
Other* 3.3
* Other included haemodialysis, drug interaction

Practice points
• Parenteral iron therapy is rarely indicated: specific indications for its use include high iron requirements
(e.g. chronic un-correctable bleeding, haemodialysis), iron malabsorption (e.g. gastric resection, coeliac
disease), intolerance of (e.g. gastrointestinal adverse effects) or poor adherence to oral iron, and
haemoglobin < 6g/dL in people who would otherwise receive a blood transfusion (e.g. those with
religious objections).2,5,7
• If parenteral iron is needed, intravenous iron is preferred because intramuscular administration is
difficult and iron is poorly absorbed from muscle.11
• Oral and parenteral iron preparations must not be prescribed together.5

11

Commentary 1
Key points
• Adolescent females are a high-risk group for
iron deficiency due to blood loss with the
onset of menstruation, and rapid growth
with increased iron requirement, often
coupled with poor iron intake due to dieting
and food faddism.
• Establishing the diagnosis of iron-deficiency
anaemia requires a full blood count and iron
studies. A blood count alone showing
hypochromic microcytic anaemia is
inadequate, as this may be due also to
thalassaemia (common in populations
originating from Mediterranean countries)
and the anaemia of inflammation.
• Iron therapy is indicated once the diagnosis
has been established. This is usually in the
form of a single daily tablet of iron in the
ferrous form, taken with orange juice on an
empty stomach. Tea should be avoided.
• Indications for parenteral iron are limited to
patients with intolerance to oral iron, non-
compliance, iron malabsorption (e.g. coeliac
disease) or ongoing blood loss due to a non-
correctable lesion.
Additional questions
Blood loss is the most relevant question. In a
female in this age group, excessive menstrual
blood loss is most likely, but GIT conditions that
may be associated with blood loss or
malabsorption should also be considered. Diet is
important, especially the intake of iron-rich
foods such as meat. Pregnancy is relevant due to
increased iron requirement. Other medications
such as aspirin or NSAIDS are important causes
of GIT blood loss. A family history of
thalassaemia would be of help interpreting the
results of the blood count and iron studies.
Investigations
Essential investigations to confirm iron-
deficiency anaemia are full blood count and iron
studies. Serum ferritin is the most important
component of iron studies, and if low, confirms
that the anaemia is due to iron deficiency. The
other components of iron studies are of value
12
Emeritus Professor Jack Metz,
Dorevitch Pathology and Honorary Consultant,
Haematology Dept, Royal Melbourne Hospital
when the ferritin is borderline; in iron deficiency
the serum transferrin is usually raised, and
percentage saturation is low. Other tests
mentioned such as serum B12/folate and ESR
are not relevant to the diagnosis. Occult blood
and coeliac screen relate to investigation of the
cause of the iron-deficient anaemia, not
diagnosis. HbH and other tests for thalassaemia
would apply only if the ferritin was normal or
raised, or there was a family history of
thalassaemia.
Most reliable marker
The most reliable marker of early iron deficiency
is the serum ferritin, but it is not a marker of
anaemia. Depletion of iron stores precedes
anaemia, but is not always accompanied by
anaemia. Transferrin saturation alone is
unreliable, as it is calculated from the serum
iron, which is subject to fluctuations unrelated
to iron status, and is also not a marker of
anaemia. The single respondent who named the
FBE is probably the most correct, as only the FBE
can establish the presence of anaemia. MCHC is
not acceptable, as the earliest change in the FBE
would be in the MCH or MCV.
Recommending drug therapy
Drug therapy should be recommended only if
the results show iron deficiency. This is the only
response that is really acceptable. In the same
way, if the test results are not available or the
diagnosis is not established, drug therapy cannot
be recommended.
Recommended medicines, frequency
and duration of therapy
Any pharmaceutical ferrous iron preparation,
but not in liquid form, is acceptable. Nutritional
supplements containing iron are not. Frequency
is daily. Duration of therapy is usually 3-6
months, but the rate of response to therapy
varies. As iron will not go into stores until the
anaemia is corrected, therapy should continue
for 3 months after the haemoglobin value
returns to normal, so that the depleted iron
stores can be replenished.
Maximising iron absorption
To maximise iron absorption, the tablet is taken
fasting and with a liquid containing vitamin C,
such as orange juice. Tea should be avoided, as
tannins inhibit iron absorption.
13
Parenteral iron
Failure to respond to adequate oral iron therapy
due to adverse effects or poor adherence are
acceptable indications for parenteral iron. High
iron need or severe anaemia are not, as there is
no evidence that the response to parenteral iron
is faster or greater than with oral iron.

Commentary 2
Key points
• Iron deficiency is common
• The cause of iron deficiency should be
identified
• The decision about which investigations to be
done are largely based on a detailed history
and examination
• Many patients in general practice who
complain of tiredness have no abnormality
on laboratory testing
• Oral iron supplements are tolerated in most
people
• Many over-the-counter preparations do not
contain sufficient elemental iron for
adequate replacement.
Additional questions
This case study is quite typical of a general
practice presentation. Mariah has a number of
possible diagnoses and iron deficiency obviously
needs to be excluded, particularly as her PR is
slightly elevated and she has pale nail beds and
conjunctiva.
It would also be important to consider other
possible secondary diagnoses such as
adjustment disorder and depression, which
could be also causing general fatigue, given her
psycho-social context with her recent migration.
In taking a history, I would enquire about diet
and in particular her red meat intake.
Simply asking if she is vegetarian may not elicit
the fact she may have a very small red meat
intake. A menstrual history is also very
important. It can be quite difficult to get an
accurate history by simply asking “are your
periods heavy?”. You may need to ask quite
specifically about flooding with clots, and if she
uses tampons, and how long before she needs
to change it. Or if she uses pads, what type of
pads — ranging from liners to maternity pads.
Some women with very heavy menses cannot
use tampons as they simply bleed around them
or will need to change them every hour. In
taking a menstrual history, it should also be
possible to evaluate if pregnancy is a potential
diagnosis.
14
Dr Pamela Burgar
MBBS (WA) Dip RACOG, General Practitioner
Eaton Medical Centre,
Eaton, Western Australia
Most respondents agreed that diet and
menstrual symptoms were the most important
issues to explore. The next symptoms of
importance to ask about are gut symptoms and
specifically upper gut discomfort, bloating,
indigestion, diarrhoea and PR blood loss. Coeliac
disease can present as iron-deficiency anaemia
but you would expect to have some abnormal
gut symptoms. In an older person, one will need
to place much more relevance on their gut
symptoms due to high risk of GI bleeding
associated with iron deficiency in this age
group4. Another common cause of iron-
deficiency anaemia is blood donation, and some
enthusiastic donators will need to pause their
donations until the iron levels have corrected
themselves. It is also important to ask about
previous medical history, family history and any
medications. It is possible that Mariah's iron
deficiency has occurred due to physiological
demands of growth during childhood (other
times of high physiological demand are during
infancy and pregnancy).
Investigations
The most relevant investigations, after taking a
history and performing an examination, are full
blood count and iron studies. Doing further or
other investigations will depend on the history
and results of the initial blood tests. One of the
great things about general practice is that you
get the opportunity to investigate further at
follow-up if the initial investigations don't fully
answer the questions. Most respondents also
chose these investigations. Doing coeliac
serology, B12 levels will depend on the either
the history or the findings of the initial
investigations.
Most reliable marker
The most reliable marker of early iron deficiency
is serum ferritin, which is very useful as a single
investigation for follow-up iron deficiency;
however, iron studies will be most useful as the
initial investigation to exclude abnormalities of
iron metabolism. Serum ferritin correlates with
total body iron stores and low levels will be seen
before serum iron is affected. Given that this
young woman is from Malta, checking for
haemoglobinopathies would also be relevant.
We don't have any results in this case study so
we don’t know the severity of her iron
deficiency but given it is giving her symptoms, it
should be corrected with oral supplementation.
Dietary modification alone to include more red
meat, grains, and leafy greens will be useful if
the iron deficiency is mild and also important to
help prevent iron deficiency recurring once it has
been treated.
Recommending drug therapy
There are a range of iron supplements and
FerroGrad C is well known and was the most
popular choice of supplementation by
respondents. It is relatively expensive, however,
and is not on the PBS, whereas FGF is.
Recommended medicines, frequency
and duration of therapy
Most patients are instructed to take one tablet
daily in order to minimise side effects. If iron-
deficiency anaemia is more severe, it may be
useful to get patients to take 2 tablets per day
to speed up the replacement. Oral iron
supplementation often has side effects but these
can often be tolerated, especially if the patient is
warned of them. The most common side effects
are constipation and black stools. If patients are
given some advice in managing these side
effects, such as increasing their water and fibre
intake, they can often tolerate the iron
supplements. The side effects are also reduced
by starting with a lower dose and gradually
increasing. Some patients more rarely get gastric
irritation and occasionally diarrhoea. It is
important to warn parents of young children
15
that iron supplements are toxic to children and
they need to be kept away from children, like all
other medications.4 It is tempting for some
patients to believe that, because they are over
the counter and a supplement, they are safe.
The guidelines vary for the duration of iron
supplementation as it will depend on severity
but most will need 3-6 months of
supplementation and longer if the iron loss is
continuing. In treating the iron deficiency it is
also important to stop it recurring; eg attending
to diet or treating menorrhagia.
Maximising iron absorption
To maximise absorption, the supplement should
be taken on an empty stomach. Taking it with
vitamin C enhances the absorption of non-heam
iron; that is, non-meat sources in vegetables and
cereals.1 The tannin in tea and coffee interferes
with the iron absorption. Taking a PPI can also
decrease iron absorption due to decreased acid
in the stomach.
Parenteral iron
Parenteral iron is recommended only when oral
supplementation has failed.3 This can occur
because of side effects, non compliance or lack
of absorption. Parenteral iron is more expensive
and not without risk. The options are for
intramuscular iron injections but the patient
needs to be warned of possible rust stains. The
staining can be minimised by using only the
buttocks and giving the injection deep into the
muscle, but this is also painful. Intramuscular
iron is poorly absorbed. The other option is for
an iron infusion, which carries a small risk of
anaphylaxis. The need for parenteral iron is
increased if there are other complicated ongoing
co-morbities such as ongoing bleeding,
heamodialysis or gastric resection.
References
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