Iron Therapy

Iron therapy is indicated only for the prevention or cure of iron deficiency. In general terms, making 25 mg of iron per day available to the bone marrow will allow an iron deficiency anaemia to respond with a rise of 1% of haemoglobin (0.15 g Hb/100 ml) per day; a reticulocyte response occurs between 4 and 12 days. An increase in the haemoglobin of at least 2 g/dl after 3 weeks of therapy is a reasonable criterion of an adequate response. Oral preparations are the treatment of choice for almost all patients due to their effectiveness, safety and low cost. Parenteral preparations should be restricted to the few patients unable to absorb or tolerate oral preparations. Red cell transfusion is necessary only in patients with severe symptomatic anaemia or where chronic blood loss exceeds the possible rate of oral or parenteral replacement.

Oral iron therapy. The goal of iron therapy is to repair the haemoglobin deficit and replenish storage iron. When oral therapy is used it is reasonable to assume that about 30% of the iron will be absorbed and to give 180 mg of elemental iron daily for 1-3 months according to the degree of anaemia. Iron stores are less easily replenished by oral therapy than by injection, and oral therapy (at lower dose) should be continued for 3-6 months after the haemoglobin concentration has returned to normal or until the serum ferritin exceeds 50 microgram/1 (or as long as blood loss continues).

Contraindications. It is illogical to give iron in the anaemia of chronic infection where utilisation of iron stores is impaired; but such patients may also have true iron deficiency. This may be difficult to diagnose without direct visualisation of stores in a bone marrow aspirate. Iron should not be given in haemolytic anaemias unless there is also haemo-globinuria, for the iron from the lysed cells remains in the body. Moreover the increased erythropoiesis associated with chronic haemolytic states stimulates increased iron absorption and adding to the iron load may cause haemosiderosis.

Iron therapy is needed in:

• Iron deficiency due to dietary lack or to chronic blood loss.

• Pregnancy. The extra iron required by mother and fetus totals 1000 mg, chiefly in the latter half of pregnancy. The fetus takes iron from the mother even if she is iron deficient. Dietary iron is seldom adequate and iron and folic acid (50-100 mg elemental iron plus folic acid 200-500 micrograms/day) should be given to pregnant women from the fourth month. Opinions differ on whether all women should receive prophylaxis or only those who can be identified as needing it. There are numerous formulations. Parents should be particularly warned not to let children get at the tablets.

• Abnormalities of the gastrointestinal tract in which the proportion of dietary iron absorbed may be reduced, i.e. in malabsorption syndromes such as coeliac disease.

• Premature babies, since they are born with low iron stores, and in babies weaned late. There is very little iron in human milk and even less in cow's milk.

• Early treatment of severe pernicious anaemia with hydroxocobalamin, as the iron stores occasionally become exhausted by the surge in red cell formation.

Oral iron preparations. There is an enormous variety of official and proprietary iron preparations. For each milligram of elemental iron taken by mouth, ferrous sulphate is as effective as more expensive preparations. It is particularly important to avoid initial overdosage with iron as the resulting symptoms may cause the patient to abandon therapy. A small dose may be given at first and increased after a few days. The objective is to give 100-200 mg of elemental iron per day in an adult (3 mg/kg in a child). Iron given on a full stomach causes less gastrointestinal upset but less is absorbed than if given between meals; however, use with food is commonly preferred to improve compliance. Commonly used preparations, given in divided doses, include:

Ferrous Sulphate Tabs, 200-600 mg/d (providing 67-195 mg/d of elemental iron) Ferrous Gluconate Tabs, 300-1200 mg daily (providing 35-140 mg/d of elemental iron) Ferrous Furmarate Tabs, 200-600 mg daily (providing 130-195 mg/d of elemental iron) Ferrous succinate and ferrous glycine sulphate are alternatives.

Choice of oral iron preparation. Oral iron is used both for therapy and for prophylaxis (pregnancy) of anaemia in people who are often feeling little if any ill-health. Because of this, the occurrence of gastrointestinal upset is particularly important as it may cause the patient to give up taking iron. The evidence as to which preparation provides best iron absorption with least adverse effects is conflicting. Gastrointestinal upset is minimal if the daily dose does not exceed 180 mg elemental iron and if iron is given with food.

A suggested course. Start a patient on ferrous sulphate taken on a full stomach once, then twice, then thrice a day. If gut intolerance occurs, stop the iron and reintroduce it with one week for each step. If this seems to cause gastrointestinal upset, try ferrous gluconate, succinate or fumarate. If simple preparations (above) are unsuccessful, and this is unlikely, then the pharmaceutically sophisticated and expensive sustained-release preparations may be tried. They release iron slowly and only after passing the pylorus, from resins, chelates (sodium iron edetate) or plastic matrices, e.g. Slow-Fe, Ferrograd, Feospan, so that iron is released in the lower rather than the upper small intestine. Patients who cannot tolerate standard forms even when taken with food may get as much iron with fewer unpleasant symptoms if they use a sustained-release formulation.

Liquid formulations are available for adults who prefer them and for small children, e.g. Ferrous

Sulphate Oral Solution, Paediatric: 5 ml contains 12 mg of elemental iron: but they stain the teeth. Polysaccharide-iron complex (Niferex): 5 ml contains 100 mg of elemental iron. There are numerous other iron preparations which can give satisfactory results.

Sustained-release and chelated forms of iron (see above) have the advantage that poisoning is less serious if a mother's supply is consumed by young children, a real hazard.

Iron therapy blackens the faeces but does not generally interfere with modern tests for occult blood (commonly needed in investigation of anaemia), though it may give a false positive with some older occult blood tests, e.g. guaiac test.

Failure of oral iron therapy is most commonly due to poor patient compliance, persistent bleeding and, as with all drug therapy, wrong diagnosis.

Adverse effects. Most patients tolerate oral iron therapy but 10-20% have symptoms that may be attributed to iron, generally gastrointestinal upset. These effects of oral iron include nausea, abdominal pain, and either constipation or diarrhoea. Upper GI effects appear to be dose-related and are best managed by ingestion of the tablet with or after food and/or reduction in the amount of iron content in each dose. This will prolong the necessary period of treatment. Diarrhoea or constipation can usually be treated symptomatically without a change in regimen.

Parenteral iron therapy

This may be required if:

• Iron cannot be absorbed from the intestine

• The patient cannot be relied on to take it or experiences intolerable gut symptoms.

Speed of haemopoietic response is not quicker than that with full doses of oral iron reliably taken and normally absorbed, for both provide as much iron as an active marrow can use, but a course of injected iron is stored and utilised over months. The ionised salts of iron given orally are unsuitable as parenteral preparations as they are powerful protein précipitants and un-ionised iron complexes are used.

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