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Diagnosing and treating iron deficiency

David I Gozzard
FRCP FRCPPath MBA
Condultant Haematologist and Medical Director Conwy and Denbighshire NHS Trust Bodelwyddan North wales

The World Health Organization defines anaemia as a haemoglobin level below 13g/dl in adult males, below 12g/dl in nonpregnant adult females and less than 11g/dl in pregnant females. But recent evidence on quality of life in anaemic patients suggests that a fall in haemoglobin to between 11g/dl and 12g/dl is the likely point for the development of symptoms.(1) Thus patients may have mild iron deficiency without symptoms and be clinically invisible to the health services.
Most adults have enough iron in their body to form a four-inch nail - three-quarters of this iron is in the blood as haemoglobin, the other quarter as iron stored in the tissues for use in red blood cell production. A significant proportion of the adult female population may have no iron stores, and this can go undetected until blood loss precipitates anaemia. Even treatment of the condition may not take into account the necessity for the replacement of iron stores and may place patients at risk of relapse of anaemia consequent upon blood loss (see Figure 1). However, the attention to agreed guidelines and judicious use of the laboratory services will generally result in timely diagnosis and optimal treatment.

Clinical presentation
Iron deficiency arises due to blood loss - generally heavy menstrual loss in females of reproductive age, occult blood loss from the gastrointestinal tract or urinary tract in other patients. A poor diet is not an acceptable primary cause of iron deficiency, although the development of iron deficiency in transfusion donors may be related to this cause.

[[NIP29_fig1_58]]

Tiredness is a common symptom seen in today's medical practice, and this alone should prompt the practitioner to ask about other possible symptoms suggestive of anaemia - easy fatigability, palpitations, irritability and pica (a change in diet or craving for unsuitable, often non-nutritive material). The most extreme case of pica I observed was a young woman with iron deficiency who ate 60 packs of ice cream wafers a day, ceasing when her iron deficiency was treated! Pallor is a very subjective sign for the diagnosis of anaemia, but conjunctival pallor should always prompt for consideration of the diagnosis. Occasionally a patient will be seen who has the unusual nail abnormalities of koilinychia - "spooned nails" (see Figure 2).

[[NIP29_fig2_58]]

The degree of anaemia that an individual can tolerate is dependent on their age, the rate of development of the anaemia and comorbidities. The most extreme anaemia from my laboratory was a 36-year-old female with heavy menstrual bleeding who walked into her GP practice with a haemoglobin of 1.8g/dl! Elderly patients with several medical conditions might tolerate only a slight fall in haemoglobin before the development of symptoms.

Investigation
The blood count is the first test to consider - anaemia with a low mean cell volume (MCV) should lead to a request for a serum ferritin test. This has been shown to be a reliable indicator of iron deficiency,(2) although it is subject to the acute-phase response (a nonspecific rise in a variety of serum proteins, including serum ferritin), producing a falsely elevated result in patients with infection, inflammation or neoplasia. In this group of patients iron deficiency can be inferred by the finding of a serum ferritin level

Treatment
First treat the cause of the iron deficiency. The anaemia itself should respond to oral iron therapy using ferrous salts, generally aiming for 100-200mg elemental iron daily as the optimal treatment. Iron intolerance is common and related to the amount of elemental iron in the preparation.(4) Ferrous sulphate 200mg twice daily is the suggested initial therapy with a reduction to once daily if side-effects of nausea, abdominal cramps or constipation occur. Although other oral iron medications are available, there is no evidence that the reduced dose of elemental iron contained therein is any better tolerated than an equivalent dose of iron delivered using oral ferrous sulphate. Similarly, modified-release iron preparations release their iron in the lower small intestine, where the iron is not easily absorbed. Compound iron and folic acid preparations should not be used to treat iron deficiency, and iron/ascorbic acid combinations are not available on the NHS.
An interesting development has been the introduction of well-tolerated intravenous iron preparations (Venofer [Syner-Med] and Cosmofer [Vitaline]). These preparations are used when oral iron therapy is not tolerated. All intravenous preparations are capable of producing allergic reactions, and administration should be medically supervised in the first instance with rapid recourse to cardiac resuscitation if required. Providing the primary care team has robust guidelines for their use and access to medical supervision, the use of these preparations in the surgery should increase with familiarity of the treatment schedules.
Response to iron therapy is predictable (see Figure 3). Providing the bone marrow is healthy, the haemoglobin rise will average 0.1g/dl/day, so the timing of the repeat blood count to ascertain response to therapy will also determine adequacy of the response. A suboptimal response can be due to continued blood loss, malabsorption or noncompliance with therapy.

[[NIP29_fig3_61]]

Treatment should be continued for three months beyond the achievement of the maximal haemoglobin. This allows for the laying down of iron stores sufficient to call upon should the cause of the iron deficiency recur.

Role of the practice and community nurse
A well-developed guideline for the investigation and treatment of iron deficiency will have a pivotal role for  the community and practice nurse. The assessment of diet, menstrual history, gastrointestinal or urological symptoms, the ordering of laboratory diagnostic tests and the counselling of patients with regard to side-effects of therapy should be part of the patient pathway. Advising the medical staff where oral intolerance occurs and the supervision of parenteral therapy will contribute to the shift to primary care-based management.

References

  1. Ludwig H, Van Belle S, Barrett-Lee P, et al. The European Cancer Anaemia Survey (ECAS): a large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients. Eur J Cancer 2004;40:2293-306.
  2. Goddard AF, James MW, McIntyre AS, et al. Guidelines for the management of iron deficiency anaemia (British Society of Gastroenterology). Gut 2000;46 Suppl 3-4:IV1-5.
  3. Calvey HD, Castleden CM. Gastrointestinal investigations for anaemia in the elderly: a prospective study. Age Ageing 1987;16:399-404.
  4. Cox TM. Iron metabolism and its disorders. In: Warrell DA, Cox TM, Firth JD, Benz EJ Jr, editors. Oxford textbook of medicine. 4th ed. Oxford: Oxford University Press; 2003.