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‘Huge advances’ in iron deficiency lead to new clinical guidance

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‘Iron deficiency is among the most common problems a GP will face in their daily practice, and yet there is definitely a view that perhaps not much has changed in the last few decades.’
 
That is Associate Professor Sant-Rayn Pasricha, who leads the World Health Organization (WHO) Collaborating Centre for Anaemia Detection and Control at the Walter and Eliza Hall Institute (WEHI).
 
He is talking to newsGP about new clinical guidance he co-authored on iron deficiency, recently published in The Lancet.
 
Associate Professor Pasricha says there have been ‘huge advances’ in the field of iron deficiency over the last decade.
 
‘But I think a lot of clinicians still just think of iron deficiency as a simple problem that you treat with iron tablets and that it’s mainly caused by nutrition deficits, and that’s it,’ he said.
 
The complexity and advances in diagnosing and managing iron deficiency have made it ‘a really exciting field’.
 
‘And [iron deficiency is] something that can be really managed a lot more efficiently than perhaps everyone appreciates,’ Associate Professor Pasricha said.
 
The authors of the paper say an underlying cause for iron deficiency should be sought ‘in all patients’ presenting with this finding.
 
Associate Professor Jason Tye-Din, a gastroenterologist at the Royal Melbourne Hospital and co-author of the paper, stresses the importance of seeking that underlying cause.
 
‘If doctors don’t take iron deficiency seriously and investigate why it is happening, serious health problems could be overlooked,’ he said.
 
‘In some cases these can be potentially life-threatening. This is something we’ve really highlighted in the review.’
 
The authors recommend screening for coeliac disease be ‘considered routinely’. Associate Professor Pasricha says that is because approximately 3% of patients with iron deficiency have coeliac disease.
 
He therefore recommends that all patients diagnosed with iron deficiency have serological testing for coeliac disease. Beyond that, it is important to consider the individual circumstances and demographics of the patient when considering the need for endoscopy.
 
Associate Professor Pasricha says the risk of gastrointestinal (GI) bleeding must be considered in postmenopausal women and men with anaemia.
 
‘And all those patients should be referred for endoscopy to exclude a serious or even malignant cause of GI bleeding,’ he said.
 
However, the need to investigate iron deficiency in premenopausal women who are still menstruating is ‘really much less clear’. Associate Professor Pasricha says premenopausal women with iron deficiency should be referred for a scope if they:

• have GI symptoms, such as abdominal pain, unexpected loss of weight, changes in bowel habits
• a family history of Gl cancer
• recurrent or refractory iron deficiency
• are not menstruating.

The paper also outlines changes that have occurred in the management of iron deficiency. Associate Professor Pasricha says these changes relate to greater understanding of the hormone hepcidin.
 
‘We now know that iron status is regulated by a hormone called hepcidin,’ he said.
 
‘Hepcidin is a master regulator that tells our body what to do with dietary iron and recycled iron, and it tells our body whether to continue to absorb iron or to block it out.’
 
Associate Professor Pasricha explains that hepcidin responds very quickly to increases in iron status.
 
‘What that means is that if you treat iron deficiency the way we used to – which is to give two to three doses of iron a day in divided, high doses – you actually wind up blocking a lot of absorption of that iron and so it’s actually quite inefficient,’ he said.
 
‘Once you understand how hepcidin is regulated, it tells you a lot about what the body is really trying to do with iron and starts opening insights into the best ways to approach diagnosis and therapy.’


Associate Professor Sant-Rayn Pasricha says there has been a rapid upsurge in the use of intravenous iron therapy to treat iron deficiency (Image: WEHI, Australia).

Associate Professor Pasricha says the most efficient way to treat mild iron deficiency is to give one dose every second day.
 
‘That would be plenty, and that’s probably going to have fewer side effects and in the long run be more efficient,’ he said.
 
Rather than turning to oral iron supplements as the mainstay of treatment for iron deficiency, Associate Professor Pasricha says intravenous (IV) iron infusions also play a significant role in management.
 
But many clinicians may still view IV iron infusions negatively due to past experience.
 
‘The older forms of iron [IV therapy] were horrendous to treat patients with,’ he said.
 
‘They were slow infusions and they carried a substantial risk of allergic reaction and introduced a really bad reputation to the treatment of iron deficiency.’
 
Associate Professor Pasricha says there are now two IV medications used in iron deficiency in Australia – ferric carboxymaltose and ferric derisomaltose – that have ‘really changed the scene’ for how this condition is treated.
 
‘These new drugs allow delivery of a very high dose of iron in just 15 minutes, which enables the total dose of iron to be replaced very fast,’ he said.
 
Associate Professor Pasricha is seeing a ‘rapid upsurge’ in the clinical use of these medications.
 
‘And I think there’s a long way to go in their use,’ he said.
 
These medications are considered second-line treatment for absolute iron deficiency, Associate Professor Pasricha said, and are useful in patients who do not tolerate or respond to oral iron therapy.
 
‘And I think they’re first-line in patients with functional iron deficiency and they’re also important in patients in whom there’s an urgent need to get their haemoglobin up; for example, in someone coming up to surgery,’ he said.
 
‘In those patients, we’d now be moving to IV iron first-line.’
 
Associate Professor Pasricha says another advance in the field of iron deficiency relates to understanding of the two main forms of the condition: absolute iron deficiency, and functional iron deficiency.
 
Absolute iron deficiency is when a person has low stores and insufficient iron in their body to make blood and supply iron to the organs.
 
‘The second form is something that we’ve come to understand better in the last few years and we call it “functional iron deficiency”,’ Associate Professor Pasricha said.
 
‘Functional iron deficiency occurs in patients with systemic inflammation and it’s the old term of “anaemia of chronic disease”.’
 
In functional iron deficiency, there is enough iron in the body but it is being locked out of the plasma because of inflammation causing an elevation in hepcidin.
 
It is now understood that inflammation causes a rise in hepcidin, which then prevents iron absorption and leads to anaemia.
 
Associate Professor Pasricha hopes the guidance outlined in this new paper will help clinicians better manage patients with iron deficiency.
 
‘We know that iron deficiency causes a large burden of disease,’ he said.
 
‘So it’s always important to think deeply about the underlying cause and develop the best management plan for these patients.’
 
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anaemia coeliac disease iron deficiency

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