Historically, the ‘gold standard’ test for diagnosis of iron deficiency was Perls’ staining of a bone marrow aspirate. Although this test is reliable, it is rarely necessary for this indication in contemporary practice.
Evaluation of the underlying cause
It is imperative that an underlying cause of iron deficiency is rigorously explored. A thorough clinical history and examination for causes of blood loss, inadequate intake or malabsorption are required.
Men and postmenopausal women with iron deficiency require evaluation for gastrointestinal blood loss and therefore should be referred to a gastroenterologist. Faecal occult blood testing has no role in the evaluation of iron deficiency anaemia as the result, whether positive or negative, does not influence consideration of endoscopic evaluation. The need for upper or lower endoscopic evaluation will be determined by the gastroenterologist on a case by case basis.
Premenopausal women often have iron deficiency because of menstrual blood loss. A gynaecological evaluation may be required to identify causes of heavy menstrual bleeding. Endoscopic gastrointestinal evaluation should also be considered in those who are aged over 50 years or have gastrointestinal symptoms or a family history of colorectal cancer, or in whom adequate oral iron therapy has failed.
Coeliac disease, autoimmune atrophic gastritis, and Helicobacter pylori infection are present in a considerable proportion of patients with iron-refractory iron deficiency.20,21 Consequently, evaluation of tissue transglutaminase antibodies (suggesting coeliac disease), antiparietal and anti-intrinsic factor antibodies (autoimmune gastritis) and H. pylori IgG is worth considering. The diagnosis of these conditions can also be confirmed by endoscopic biopsy.
Rarely, conditions that cause chronic intravascular haemolysis can lead to iron deficiency anaemia. These include haemolysis due to mechanical heart valves, direct trauma (sometimes referred to as runners’ or march haemolysis), paroxysmal nocturnal haemoglobinuria and paroxysmal cold haemoglobinuria. The remaining causes of intravascular haemolysis generally manifest more acutely, before the consequences of iron deficiency become apparent. A haemolytic screen, including assessment of a blood film, direct antiglobulin test, measurement of lactate dehydrogenase, haptoglobin, reticulocyte count and urinary haemosiderin test will help identify haemolysis. If there is concern about haemolysis then prompt haematological referral is advisable.
Rare hereditary forms of iron deficiency anaemia exist, the most common of which is termed iron-refractory iron deficiency anaemia. This is an autosomal recessive disorder that manifests with hypochromic microcytic anaemia in the presence of a normal or elevated ferritin level and thus can be confused with anaemia of chronic disease. The diagnosis and management of patients with this form of anaemia require input from a haematologist.
In summary, the cause of iron deficiency should be established and treated in parallel with the therapeutic correction of the iron deficiency. Where necessary, specialist opinion should be obtained.
Treatment of iron deficiency
Oral iron therapy
Oral iron salts, including ferrous sulfate, ferrous fumarate and iron polymaltose, are the mainstays of oral iron replacement. Oral iron is affordable, accessible and effective. Common side effects include gastrointestinal upset, manifesting as constipation, diarrhoea, abdominal cramps, dark thick stool and an altered sense of taste. These side effects are common, occurring in up to 50% of patients who trial oral iron therapy, and compromise adherence in many cases.
Provided iron deficiency anaemia does not require rapid correction, a trial of oral therapy is an appropriate first-line strategy. A standard oral dose for adults is 100 to 200mg of elemental iron per day. Larger doses will be better tolerated if divided (e.g. 50mg elemental iron three times daily). Currently available oral iron preparations for the treatment of iron deficiency in adults are outlined in Table 1.
Practice tips for the use of oral iron preparations are summarised in Box 3. Administration on an empty stomach allows gastric acid to assist with oral iron absorption. Administration with vitamin C can further facilitate absorption. Conversely, ingestion with tea, calcium or antacids can limit absorption. A simple strategy to ameliorate gastrointestinal side effects is to try dosing with meals; although this may compromise absorption it may facilitate adherence and thus have an overall positive effect on therapy. There is some evidence to suggest that dosing every second day is at least as effective as daily dosing and potentially more effective.22 Thus, it is reasonable to decrease dose frequency in an effort to maximise tolerance and thus adherence. As previously mentioned, larger doses may be better tolerated if divided. If constipation occurs then an oral iron elixir is a useful option. It is worthwhile reassuring the patient that if oral therapy is not tolerated an iron infusion will be made available.