Iron deficiency anaemia

Published in MedicineWise News

Date published: About this date

Clinical content may change after this date. This information is not intended as a substitute for medical advice from a qualified health professional. Health professionals should rely on their own expertise and enquiries when providing medical advice or treatment.

Iron deficiency anaemia affects people of all ages in the developed and developing world.1 It can occur at all stages of life: Australian population groups at increased risk include women of childbearing age (particularly those who are pregnant) and children. This News discusses causes, investigation and management of iron deficiency anaemia. Management includes identifying and addressing the underlying cause(s), and correcting iron deficiency with effective iron therapy including dose and duration.

Always establish the cause(s) of iron deficiency anaemia

Establishing the cause(s) of iron deficiency anaemia is essential so that serious disease is not overlooked (e.g. gastric or colon cancer) as well as to prevent further iron imbalance and provide appropriate therapy. Likely causes vary according to factors such as age, co-morbidities and medicines use.2,3 Causes may be physiologic (e.g. increased iron demand because of pregnancy) or pathologic (e.g. increased iron loss because of bleeding, decreased iron absorption because of coeliac disease) (Box 1). Consider referral to a gastroenterologist to investigate suspected gastrointestinal blood loss: this is the most common cause of iron deficiency anaemia in men and postmenopausal women.4-6

Box 1: Some common causes of iron deficiency anaemia4,7

Increased iron demand
Increased iron demand
Decreased iron intake/absorbtion
Rapid growth (e.g. infant, adolescent)
Pregnancy
Erythropoietin therapy
Gastrointestinal blood loss:
  • drug therapy (e.g. aspirin, NSAID)
  • cancer (e.g. colon, gastric)
  • gastric ulcer
  • infection (e.g. hookworm)
  • angiodysplasia
Non-gastrointestinal blood loss:
  • menstrual
  • blood donation
Malabsorption resulting from
  • disease (e.g. coeliac disease)
  • surgery (e.g. post-gastrectomy)
  • inflammation
Hypochlorhydria/achlorhydria (e.g. long
term proton pump inhibitor therapy)
Inadequate diet (e.g. vegan)

Investigating possible iron deficiency anaemia

When investigating possible iron deficiency anaemia, start with a full history and examination. Assess the patient's symptoms and signs, diet, medicines and other possible causes of iron deficiency anaemia (see Box 1).4,8 Other possible causes of hypochromic microcytic anaemia (low haemoglobin, low mean cell haemoglobin [MCH] and low mean cell volume [MCV]4) to consider include thalassaemia, anaemia of chronic disease and sideroblastic anaemia.7

Low serum ferritinA— not low serum iron — is the most useful marker of early iron deficiency. Serum ferritin most accurately reflects the body's iron stores and a low level can be seen before serum iron is affected.9 However, be aware that serum ferritin is an acute phase reactant and may be normal or high with iron deficiency in infective, inflammatory, malignant or hepatic diseases.2 Iron studiesB measuring serum ferritin, iron and transferrinC in combination reduce the likelihood of an incorrect diagnosis. A low serum iron with a high transferrin can indicate iron deficiency anaemia. However, be aware that a low serum iron and transferrin may be caused by inflammation or other diseases.9 Interpreting iron studies can be complex and expert advice may be needed.

A. MBS item 66593: measures serum ferritin.
B. MBS item 66596: measures serum ferritin, iron and transferrin/iron binding capacity.
C. Indirectly measured by total iron binding capacity.

The ins and outs of oral iron

Oral iron is first line therapy for most people with iron deficiency anaemia provided that the dose and duration are adequate. Doses differ for adults and children (Box 2). There are more than 100 oral preparations containing iron available over the counter in Australia but few contain enough iron to treat iron deficiency anaemia (Table 1). Remind people that small children can overdose on even a small amount of an iron preparation and to store iron in a locked cabinet out of a reach and sight of children.2,6

Oral iron is absorbed poorly but more completely on an empty stomach 1 hour before or 2 hours after food.2,7 However, if oral iron upsets the stomach it can be taken with or shortly after food.2 Other ways to minimise stomach upset are to start at a low dose and gradually increase as tolerated (e.g. start with alternate daily dosing then increase to daily or twice daily dosing) or give smaller, more frequent doses (e.g. use oral liquid in divided doses).

Box 2: Usual elemental iron doses for treating iron deficiency anaemia2,6

Oral doses

Adult: 100–210 mg daily in divided doses

Child: 2–3 mg/kg up to 7 mg/kg (maximum 210 mg) daily in divided doses

Table 1: Iron preparations used for treating iron deficiency anaemia2,10

Dose form
Elemental iron
Iron saltD
Combined with
Brand name
PBS general
benefit
CR tablet
105 mg
dried ferrous sulfate 325 mg

Ferro-Gradumet

CR tablet
80 mg
dried ferrous sulfate 250 mg
folic acid 300 microgram
FGF

CR tablet
105 mg
dried ferrous sulfate 325 mg
ascorbic acid 500 mg
Ferrograd C

Capsule
87.4 mg
dried ferrous sulfate 270 mg
folic acid 300 microgram
Fefol

Tablet
100 mg
ferrous fumarate 310 mg
folic acid 350 microgram
Ferro-F

Oral liquid
6 mg/mL
ferrous sulfate 30 mg/mL

Ferro-Liquid

InjectionE
20 mg/mL
iron sucrose (5 mL ampoule)

Venofer
Injection
50 mg/mL
iron polymaltose (2 mL ampoule)

Ferrosig
Ferrum H
 
D. 1 mg elemental iron is approximately equivalent to: ferrous fumarate 3 mg, dried ferrous sulfate 3 mg, ferrous sulfate (non-dried, heptahydrate) 5 mg.
E. See Specific indications for parenteral iron or the PBS website for more information.

Duration of oral iron therapy

The two goals of iron therapy are to correct iron deficiency anaemia and to replenish iron stores.7 Correcting iron deficiency anaemia takes 2–4 months if appropriate doses of iron are used and the underlying cause is managed.8 Confirm initial response to iron therapy by checking haemoglobin, usually after 2–4 weeks.2,5,8 Haemoglobin should rise 20 g/L over 3–4 weeks.2 Haemoglobin should be normal at 2–4 months.5 If there is no change in haemoglobin: assess and manage adherence to and tolerance of iron therapy, review the diagnosis and consider the possibility of ongoing problems (e.g. bleeding).2,5 Consider seeking specialist advice if there is no likely cause for a lack of response.5 Replenishing iron stores takes longer than correcting iron deficiency anaemia.3 Recommendations vary but it is reasonable to continue iron for another 3–6 months after haemoglobin is normal.2,4,5,8

Adverse effects of oral iron

Common adverse effects of oral iron may lead to poor adherence. These include dose related gastrointestinal effects (e.g. abdominal pain, nausea, vomiting, constipation and diarrhoea) and black discolouration of faeces.2,6 The oral liquid may cause black discolouration of teeth: this can be prevented by diluting with water and drinking through a straw.2

Oral iron can cause drug interactions

Iron can form poorly soluble complexes with other drugs causing reduced absorption (Table 2). Advise people to avoid taking iron with tea or coffee because tannins can reduce absorption, apparently because of complex formation.11

Table 2: Some drug interactions with oral iron2,11

Drug and its effect
How to manage the interaction
Iron absorption is reduced by:  

antacids

separate dosage times by as long as possible

calcium (e.g. in dairy products such as milk) separate dosage times by several hours
Iron reduces the absorption of:
 

oral bisphosphonates (e.g. alendronate, clodronate, etidronate, ibandronic acid, risedronate, tiludronate)

do not take iron within 2 hours of taking an oral bisphosphonate

levodopa, carbidopa separate dosage times by as long as possible
methyldopa separate dosage times by 2 hours; monitor BP and adjust methyldopa dose if necessary
thyroid hormones (e.g. liothyronine, thyroxine)
separate dosage times by 4–5 hours
Iron absorption is reduced and iron reduces the absorption of:
 

oral quinolones (e.g. ciprofloxacin, moxifloxacin, norfloxacin)

take quinolone at least 2 hours before iron

tetracyclines (e.g. doxycycline, minocycline) separate dosage times by as long as possible (at least 2 hours)

Specific indications for parenteral iron

Parenteral iron can usually be avoided if oral iron is increased gradually from a low starting dose, and if ongoing iron losses (e.g. blood loss) are addressed.6 If parenteral iron therapy is indicated, the intravenous route is preferred because intramuscular iron is painful, stains skin and is poorly absorbed.2,6 There are specific indications for parenteral iron therapy such as intolerance of (e.g. gastrointestinal adverse effects), poor adherence to or lack of efficacy of oral iron (despite changing dose, frequency), malabsorption (e.g. coeliac disease) or high iron need (e.g. haemodialysis, ongoing blood loss).2,3

Intravenous iron is used two ways:

  • to give the total amount of iron required (as iron polymaltose) in a single infusion to correct the haemoglobin deficit and replenish iron stores
  • as repeat small doses of iron (as iron polymaltose or iron sucrose) over a long time (e.g. haemodialysis).7

Iron polymaltose and iron sucrose are available in Australia (Table 1) and are dosed according to the unit protocol or product information. Anaphylaxis is a rare adverse effect: some people undergoing chronic haemodialysis who have had an anaphylactic reaction to iron polymaltose can access iron sucrose with a PBS authority.10

People at risk of iron deficiency anaemia

Although there are some population groups at risk, evidence to guide management is often lacking. Routine iron therapy is not recommended in pregnant women.2,12 Check haemoglobin at the first antenatal visit and then about 28 weeks gestation.12 Investigate and treat any anaemia that is detected. Iron deficiency anaemia can occur during pregnancy because of increased iron demand. Although most Australian children do not need routine iron therapy, they may be at risk of developing iron deficiency anaemia during periods of rapid growth. The effect of iron therapy to improve the associated psychomotor and cognitive abnormalities is unclear at present.13,14 About 1 in 60 community dwelling white Americans > 65 years are estimated to have iron deficiency anaemia15 and it may be more prevalent among those in hospitals or institutions.3,16 Although Australian prevalence data are lacking, chronic occult gastrointestinal blood loss and malnutrition are common causes.3,17 Treat with iron therapy when appropriate.

Encourage adequate dietary iron intake

Adequate dietary iron is important for prevention but is insufficient to treat iron deficiency anaemia. The recommended daily iron intake varies with gender and age: it is highest for pregnant and premenopausal women (27 mg and 18 mg daily respectively).18 Encourage iron intake from both haem and non-haem sources (Box 3). Consider referral to a dietitian if insufficient dietary iron intake is suspected.5 See the Gastroenterology Society website for consumer information about iron deficiency.

Box 3: Examples of iron-rich foods (mg of iron/100 g food portion)6,19

Haem iron sources
offal
lamb kidney
11 mg
lean red meat
lean casserole beef
3 mg
fish
canned tuna
1 mg
chicken
lean baked thigh fillet
1 mg
Non-haem iron sources
grains and cereals
wholemeal bread
2 mg
leafy green vegetables
English spinach
4 mg
legumes
mixed canned beans
2 mg
eggs
hard boiled
2 mg
Expert reviewer

Associate Professor Anthony Dodds

Director, Haematology and Bone Marrow Transplantation

St Vincent’s Hospital, Sydney

Reviewers

Dr James Best, General Practitioner, Sydney

A/Prof Nick Buckley, Consultant Clinical Pharmacologist and Toxicologist, University of New South Wales

Jan Donovan, Consumer Representative

Dr John Dowden, Editor, Australian Prescriber

Dr Graham Emblen, General Practitioner, Toowoomba

Deborah Norton, QUM Pharmacist, West Vic DGP

Susan Parker, Pharmacist, Sydney

Dr Jane Robertson, Senior Lecturer, Discipline of Clinical Pharmacology University of Newcastle

Simone Rossi, Managing Editor, Australian Medicines Handbook

Dr Guan Yeo, Clinical Education Consultant and General Practitioner, Berowra

Any correspondence regarding content should be directed to NPS. Declarations of conflicts of interest have been sought from all reviewers. The opinions expressed do not necessarily represent those of the reviewers.

References
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  19. Food Standards Australia and New Zealand. NUTTAB 2006: Australian Food Composition Tables. Canberra: FSANZ, 2006. (accessed 8 July 2010).