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Managing iron deficiency anaemia

Iron deficiency is a common presentation in primary care and is a leading cause of anaemia. Dr Gwynne and Dr Nandi describe the symptoms, causes and treatment of iron deficiency and the importance for primary care nurses to be aware of how easy it is for this condition to develop

MVP Gwynne
MB BS BSc Hons
Staff Grade
Department of Haematology

AC Nandi
FCRP FRCPath
Consultant Haematologist
Surrey & Sussex Healthcare NHS Trust

Iron deficiency anaemia was first described in Egypt as long ago as 1500 BC. In medieval times it was known as chlorosis and, by the seventeenth century, was treated with iron salts.
Today iron deficiency is a leading cause of anaemia; between 2% and 5% of adult men and postmenopausal women in the developed world are known to have this condition.(1-3) In premenopausal women, menstrual losses and increased demands in pregnancy, coupled with losses at delivery are the main causes of iron deficiency, while gastrointestinal blood loss is the major cause in adult men and postmenopausal women.(4-8)
In total, it is estimated that 500 million people worldwide are afflicted with iron deficiency anaemia. 
   
Anaemia
The World Health Organization defines anaemia as a haemoglobin below 13 g/dl in men older than 15 and less than 12 g/dl in nonpregnant women above the same age. In pregnant women, a haemoglobin of less than 11 g/dl is considered anaemic.(4-8)
  
Iron
Most iron is found in the haemoglobin of red blood cells, myoglobin in muscles and in the serum, directly bound to proteins such as transferrin, ferritin and haemosiderin. There is also iron stored in macrophages in the spleen, bone marrow and liver.
Iron is present in vegetables and meat, but more so in meat; the average omnivorous diet contains about 10-20 mg of iron daily of which approximately 1 mg is absorbed.

Iron deficiency
There are several tests available to assess iron deficiency. Low iron, raised total iron-binding (TIBC) (and low ferritin) would indicate iron deficiency; whereas, low iron, low TIBC (and normal or raised ferritin) would suggest the so-called anaemia of chronic disorder (see Table 1).

[[nip41_table1_44]]

As iron deficiency anaemia develops, characteristic changes in the blood film occur: microcytosis - low MCV (mean cellular volume); hypochromia - low MCH (mean cell haemoglobin) and MCHC (mean cell haemoglobin concentration); anisocytosis (variable red blood cell size); pencil cells; and target cells. There may be an increase in the platelet count; the reason for this is not known, but may indicate a chronic blood loss, eg, occult gastrointestinal bleeding.
The symptoms of anaemia vary greatly and can seem very nonspecific: 

  • Tiredness.
  • Shortness of breath on exertion.
  • Worsening angina.
  • Palpitations.

Poor concentration in children has also been noted. With increasing anaemia the signs of pallor (especially in the conjunctiva), nail changes, eg, koilonychia (see Figure 1) angular stomatitis, glossitis (see Figure 2) and alopecia may occur.

[[nip41_fig12_46]]

A curious manifestation of iron deficiency is pica, which is a craving to eat unusual substances, eg, clay, ice, coal or even soil. The reason for this is unknown.

A summary of the causes of iron deficiency
Chronic blood loss

  • Menorrhagia.
  • Repeated pregnancies in close succession.
  • Peptic ulceration.
  • Angiodysplasia.
  • Aspirin.
  • Carcinoma of the stomach or bowel.
  • Piles.
  • Inflammatory bowel disease.
  • Diverticulitis.
  • Haematuria (rarely).
  • Clotting problems or warfarin therapy.

Increased iron demands

  • Prematurity.
  • Growth spurts.
  • Pregnancy.
  • Chronic renal failure patients on erythropoietin and/or dialysis.

Iron-poor diet    

  • Vegetarianism/veganism.
  • Poor general diet.

Malabsorption

  • Gluten-induced enteropathy.
  • Coeliac disease.
  • Gut infestation, eg, hookworm (globally the commonest cause of iron deficiency).
  • Total/partial gastrectomy.

Management of iron deficiency anaemia
The first and most important step is to look for the cause of the deficiency and to eliminate this. Treatment can then be started.

Oral therapy
Oral therapy is the preferred option and a standard dose of 200 mg ferrous sulphate TDS is usually sufficient. In children the treatment is weight-related, and 3 mg/kg (usually in liquid form) is recommended. Other oral iron salts are available, eg, ferrous fumarate and can be as effective.
Gastrointestinal side-effects may occur in 10-20% of patients experiencing nausea, constipation, diarrhoea or epigastric discomfort. These tend to be dose-related and may be improved by reducing the dose.
Enteric coated or slow release preparations are not advised as these bypass the duodenum before the iron is released.
Factors promoting the absorption of iron include vitamin C (eg, orange juice). Tea has the opposite effect as do alkali preparations and phytates found in nuts, cereals, legumes and seeds.
In compliant patients a rise in the Hb of 2 g/dl would be expected within three weeks. Treatment should continue for three to six months and the ferritin levels should return to normal levels.
There are a number of other products on the market, which anecdotally have also shown to be of benefit to patients unable to tolerate conventional iron supplements. These include Spatone and Floradix, natural iron supplements that are widely available from health shops or via the internet. These appear to be well tolerated especially in pregnant women as they do not cause constipation or gastrointestinal upset. However, there are no clinical trials to support their use.
Once the cause is removed (ongoing blood loss, malabsorption etc), failure to respond may be due to noncompliance, or comorbidities such as renal failure, liver disease or malignancy.

Parenteral iron therapy
If an oral therapy is not appropriate or unsuccessful, eg, malabsorption, then parenteral iron may be required.

Intramuscular iron
Over recent years, intramuscular (IM) iron has not been commonly used in the UK as there has been no licensed product available. However, Cosmofer [Vitaline] is now licensed to be given intramuscularly as a series of undiluted injections at a dose of 2 ml each time. If the patient is fairly active, these can be administered daily until the whole dose is received; in bedridden or inactive patients the frequency of injections should be reduced to once or twice weekly. As with the intravenous administration, a test dose beforehand is recommended (see below). The injection can be painful, but is useful in patients unable to comply with an intravenous procedure or where venous access is difficult. It might also prove useful in patients unable to attend hospitals for the intravenous form. In cases where IM iron is used, unexposed areas of skin are preferred (eg, the upper outer quadrant of the buttock), and it is given as a deep intramuscular injection. The Z-track technique, where the skin is displaced prior to injection, should be employed and a few seconds should be allowed before withdrawing the needle to allow the muscle to accommodate the injection volume. To reduce leakage along the injection track, the patient is encouraged not to rub the site. This minimises staining, which if it does occur will happen on a site not usually seen in public.

Intravenous iron
There are two main intravenous preparations, Venofer [Syner-Med] and Cosmofer, both of which are ferric hydroxide complexes providing 20 mg/ml and 50 mg/ml of iron respectively. There is a risk of anaphylaxis with both products and so a small test dose under medical supervision is recommended. Flushing, nausea, shivering and urticaria can occur as milder allergic reactions, but in the more extreme cases, bronchospasm, and syncope can occur.
There are also a number of delayed reactions, but these are usually much less severe and can include arthralgia, fever and lymphadenopathy which can last for several days.

Case study 1: A case of iron deficiency
Mrs L is a 62-year-old nurse with long standing ulcerative colitis and polymyalgia rheumatica.
Due to her inflammatory bowel disease, she is unable to absorb adequate oral iron and also has gastrointestinal side-effects. At presentation, her results were as follows:

  • Haemoglobin, 13.1 g/dl (normal).
  • MCV, 94 fl (normal).
  • Ferritin, 9 mcg/l (normal range 15-150 mcg).
  • Serum iron, 11 microµmol/l (normal range 11-28 mcg/l).

In spite of her normal haemoglobin, Mrs L felt excessively tired and so was offered an infusion of iron. Using the chart, the Cosmofer dose was calculated based on the patient's weight and baseline Hb. An initial test dose of 25 mg of iron was infused as a test dose over 30 minutes, and then after an interval of one hour, during which time no adverse reaction was seen, the remainder of the dose was given.
A little over a month later, the haemoglobin had increased to 14.8 g/dl and the ferritin levels to 106 mcg/l. The serum iron rose to just above the lower limits of normal to 14 µmol/l and the patient felt much better expressing higher levels of energy.
As this is an ongoing problem, Mrs L has been seen a number of times since. It is worth noting, however, that along with many other patients, not all of the criteria for iron deficiency were fulfilled and she never became anaemic.

Case study 2: A case of iron deficiency anaemia
The second case is a vegetarian Asian lady, Mrs V, in her late forties, who presented with a classical picture of iron deficiency anaemia:

  • Haemoglobin, 10.9 g/dl.
  • MCV, 77 fl (normal range 82-98 fl).
  • MCH, 24.8 pg (normal range 27.3-32.6 pg).

Her iron studies revealed a classical picture of low serum iron (5 µmol/l), low ferritin (2 mcg/l), TIBC 71 (normal range 41-77) and a percentage saturation of transferrin of 7% (normal range 15-51%).
Mrs V was symptomatic with these parameters, describing tiredness, shortness of breath on exertion, and occasional palpitations. She was also looking very pale and had a sore mouth.
Having excluded thalassaemia, Cosmofer was infused with the usual precautions. A month later, the readings showed a marked improvement:

  • Hb, 12.9 g/dl.
  • MCV, 85 fl.
  • MCH, 27.7 pg.
  • Serum iron, 10 µmol/l.
  • Ferritin, 111 mcg/l.
  • Saturation 22%.

As a vegetarian, iron deficiency might well be an ongoing problem especially as she was intolerant to oral preparations. In certain ethnic groups it is important to exclude thalassaemia trait as a cause for a microcytic anaemia, and it is also important to remember that strict vegetarians may have complex anaemia due to the coexistence of vitamin B12 deficiency.

Conclusion
Iron deficiency is a common disorder where the balance of available dietary iron may be less than that required to cover obligatory losses. If intake is reduced due to dietary restrictions or ill-health, or demands on iron are increased due to blood loss or pregnancy, iron deficiency anaemia will result. The primary care nurse should always be aware of how easy it is for this insidious condition to develop. Consider dietary changes such as promoting absorption with vitamin C, restricting tea at meal times, and avoiding alkali antacid medication in the first instance. Iron supplementation, if required, may need to be tailored to the individual's needs depending on the degree of deficiency, product tolerability and patient preference.

References

  1. Calvey HD, Castleden CM. Gastrointestinal investigations for anaemia in the elderly: a prospective study. Age Ageing 1987;16:399-404.
  2. Sayer JM, Long RG. A perspective on iron deficiency anaemia. Gut 1993;34:1297-9.
  3. McIntyre AS, Long RG. Prospective survey of investigations in outpatients referred with iron deficiency anaemia. Gut 1993;34:1102-7.
  4. Kepczyk T, Kadakia SC. Prospective evaluation of gastrointestinal tract in patients with iron-deficiency anemia. Dig Dis Sci 1995;40:1283-9.
  5. Rockey DC, Cello JP. Evaluation of the gastrointestinal tract in patients with iron-deficiency anemia. N Engl J Med 1993;329:1691-5.
  6. Cook IJ, Pavli P, Riley JW, et al. Gastrointestinal investigation of iron deficiency anemia. BMJ 1986;292:1380-2.
  7. Zuckerman GR, Benitez J. A prospective study of bidirectional endoscopy (colonoscopy and upper endoscopy) in the evaluation of patients with occult gastrointestinal bleeding. Am J Gastroenterol 1992;87:62-6.
  8. Hardwick RH, Armstrong CP. Synchronous upper and lower gastrointestinal endoscopy is an effective method of investigating iron-deficiency anaemia. Br J Surg 1997;84:1725-8

Further reading
British Society of Gastroenterology. Guidelines for the management of iron deficiency anaemia. London: BSG; 2000.
Hughe-Jones NC, Wickramasinghe SN, Hatton C. Lecture notes on haematology. 7th ed. Oxford: Blackwell; 2004.

Hoffbrand V, Petit JE, Moss PAH. Essential haematology.  5th ed. Oxford: Blackwell; 2006.