Iron deficiency anaemia
Published in MedicineWise News
Date published: About this date
- Investigate possible iron deficiency anaemia
- The ins and outs of oral iron
- Specific indications for parenteral iron
- People at risk of iron deficiency anaemia
- Encourage adequate dietary intake
- Case study 66: Iron deficiency anaemia
- Gastroenterology Society - for consumer information on dietary iron
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)
Gastrointestinal blood loss:
Malabsorption resulting from
term proton pump inhibitor therapy)
Inadequate diet (e.g. vegan)
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.
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
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
||dried ferrous sulfate 325 mg
||dried ferrous sulfate 250 mg
||folic acid 300 microgram
||dried ferrous sulfate 325 mg
||ascorbic acid 500 mg
||dried ferrous sulfate 270 mg
||folic acid 300 microgram
||ferrous fumarate 310 mg
||folic acid 350 microgram
||ferrous sulfate 30 mg/mL
||iron sucrose (5 mL ampoule)
||iron polymaltose (2 mL ampoule)
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:|
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.
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
|lean red meat
||lean casserole beef
||lean baked thigh fillet
|Non-haem iron sources|
|grains and cereals
|leafy green vegetables
||mixed canned beans
Associate Professor Anthony Dodds
Director, Haematology and Bone Marrow Transplantation
St Vincent’s Hospital, Sydney
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.
- World Health Organization. Worldwide prevalence of anaemia 1993–2005: WHO Global Database on Anaemia. Geneva: WHO Press, 2008. (accessed 21 May 2010).
- Australian Medicines Handbook. Adelaide: Australian Medicines Handbook Pty Ltd, 2010.
- Clark SF. Iron deficiency anaemia. Nutr Clin Pract 2008;23:128–41.
- Goddard AF, James MW, Mcintyre AS, et al. Guidelines for the management of iron deficiency anaemia. Loughborough: British Society of Gastroenterology, 2005. (accessed 8 February 2010).
- Sowerby Centre for Health Informatics at Newcastle (SCHIN). Anaemia - iron deficiency. Clinical Knowledge Summaries. Newcastle upon Tyne, UK: National Institute for Health and Clincal Excellence, 2009. (accessed 24 February 2010).
- Gastrointestinal Writing Group. Therapeutic Guidelines: Gastrointestinal, Version 4 Updated March 2010 [eTG complete CD-ROM]. Melbourne: Therapeutic Guidelines Ltd, 2006.
- Fauci AS, Kasper DL, Longo DL, et al, eds. Harrison's Principles of Internal Medicine. 17th edn. New York: McGraw-Hill, 2008.
- Guidelines and Protocols Advisory Committee. Investigation and management of iron deficiency. Victoria: British Columbia Medical Association, 2004. (accessed 2 June 2010).
- Firkin F, Rush B. Interpretation of biochemical tests for iron deficiency: diagnostic difficulties related to limitations of individual tests. Aust Prescr 1997;20:74–6.
- Department of Health and Ageing. PBS for Health Professionals. Canberra, 2010. (accessed 8 June 2010).
- Baxter K, ed. Stockley's Drug Interactions. 8th edn. London: Pharmaceutical Press, 2008.
- Royal Australian and New Zealand College of Obstetricians and Gynaecologists. C-Obs25: Vitamin and mineral supplements in pregnancy. RANZCOG college statement. Melbourne: RANZCOG, 2008. (accessed 12 August 2010).
- Sachdev HPS, Gera T, Nestel P. Effect of iron supplementation on physical growth in children: a systematic review of randomised controlled trials. Public Health Nutr 2006;9:904–20.
- Martins S, Logan S, Gilbert RE. Iron therapy for improving psychomotor development and cognitive function in children under the age of three with iron deficiency anaemia. Cochrane Database Syst Rev 2001: CD001444.
- Guralnik JM, Eisenstaedt RS, Ferrucci L, et al. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood 2004;104:2263–8.
- Woods JL, Walker KZ, Juliano-Burns S, et al. Malnutrition on the menu: nutritional status of institutionalised elderly Australians in low-level care. J Nutr Health Aging 2009;13:693–8.
- Andres E, Federici L, Serraj K, et al. Update of nutritient-deficiency anaemia in elderly patients. European J Intern Med 2008;19:488–93.
- National Health and Medical Research Council. Nutrient reference values for Australia and New Zealand Including recommended dietary intakes. Canberra: Department of Health and Ageing, 2006. (accessed 24 February 2010).
- Food Standards Australia and New Zealand. NUTTAB 2006: Australian Food Composition Tables. Canberra: FSANZ, 2006. (accessed 8 July 2010).