With successful oral therapy, reticulocytosis will be evident after approximately 72hours, and a haemoglobin increment of 10g/L every 10 days should be expected. Ensure that the patient is vitamin B12 and folate replete to allow rapid red blood cell production. Treatment should be continued for three to six months after normalisation of haemoglobin. Another strategy is to continue until a ferritin target level of 100ng/mL (unaffected by inflammation) is reached to ensure repletion of iron stores.15,23
Parenteral iron therapy
Intravenous (IV) iron is a useful option for patients who are intolerant or unresponsive to oral iron therapy or require more rapid normalisation of iron stores and anaemia, such as before surgery or in the later stages of pregnancy. Additional uses of IV iron include treatment of functional iron deficiency seen in anaemia of chronic inflammation and chronic kidney disease, particularly when erythropoiesis-stimulating agents are being used.
Currently available IV iron preparations for the treatment of iron deficiency in adults are outlined in Table 2. They are safe, with low rates of serious adverse events and well-described methods for patient selection, risk minimisation and adverse event management.15,24-26 Historically, medical education warned of the risk of iron infusions, but this was in the era of iron dextran infusions. Ferric carboxymaltose, iron polymaltose and iron sucrose have markedly lower rates of infusion reactions.24 Headache is the most commonly reported adverse drug reaction, occurring in 3.3% of patients. Flushing and nausea reportedly occur at rates between one in 10 and one in 100, and other reactions such as fever, myalgia and arthralgia at rates between one in 100 and one in 1000.27
Practice tips for the use of IV iron preparations for the treatment of iron deficiency in adults are summarised in Box 4. Ferric carboxymaltose allows 1000mg of iron to be administered within 15 minutes and thus makes outpatient administration feasible. Specialist advice should be obtained before use of IV iron in children. In adults, doses should not exceed 1000mg per week. If more iron is required then the dose can be repeated at intervals no shorter than one week apart. Iron polymaltose and iron sucrose are alternative parenteral preparations, but ferric carboxymaltose is increasingly preferred because of its shorter infusion time.
The National Blood Authority of Australia has outlined a simplified method for calculating body iron deficit in people weighing 35kg or over, albeit with a recommendation of caution because of limited experience with its use (Table 3).28
Side effects of parenteral therapy include taste alteration, nausea, headache, hypertension, arthralgia, myalgia, fever, flushing and hypersensitivity reactions. In addition, parenteral iron can result in permanent, cosmetically significant skin staining. This can occur when intravenous doses extravasate (and the dose is delivered into the soft tissue) or when the dose is given intramuscularly. It is important that this complication is mentioned during the consent process, and it further highlights the importance of appropriate monitoring during infusion therapy. Additional complications of intramuscular iron include pain and a local inflammatory response. With the availability of well-tolerated IV preparations, the role of intramuscular iron is now limited. Iron sucrose and ferric carboxymaltose should not be given intramuscularly.
Diet alone is generally inadequate to replace iron stores in a patient with iron deficiency, but general dietary advice is useful to help management of patients with early iron deficiency and to prevent recurrence.29 Patients can be guided to more iron-rich foods, both animal based and non-haem iron.
Red blood cell transfusion
Red blood cell transfusion should be reserved for patients with iron deficiency anaemia of a severity that is not tolerated by the patient. The transfusion threshold varies from patient to patient. However, if the anaemia is of gradual onset and the patient is well compensated then both oral and IV iron can generally lead to adequate haemoglobin increments without exposing the patient to transfusion-related adverse events. For example, otherwise well women of childbearing age can generally be spared the risks of transfusion, including alloimmunisation (the formation of antibodies) that may complicate future pregnancies. In the few patients who require transfusion, the aim of transfusion should be to relieve symptoms with as few units of blood as possible, rather than to normalise the haemoglobin level. Iron replacement therapy remains a priority in patients who have received a transfusion, as the iron content of blood is insufficient to correct iron deficiency.
Infants and children
Infants, toddlers and children are all at risk of iron deficiency, owing to their high physiological need for iron for sustained growth. There is reasonable concern about a possible association between iron deficiency in childhood and long-term adverse neurocognitive outcomes and behavioural difficulties.30