Clinical Problem:

Unfortunately Fe studies continue to be badly interpreted and, subsequently, patients treated inappropriately. I see a large amount of patients who are very confused as to whether they are iron deficient – who have normal iron stores. This is bread and butter stuff so lets very quickly remove some rust.

Question 1 – Does iron deficiency cause symptoms in adults?

Wow I thought this would be an easy first question – but it is not!

There is no debate the iron deficiency ANAEMIA (IDA) causes fatigue, but there is conflicting evidence online about whether just being low in iron causes fatigue IN ADULTS.

Three small studies suggest symptoms of fatigue and, perhaps, effects on neurocognition in young women who are iron deficient (CMAJ 2012 – Link, Blood 2011 – Link, J Am College of Nutrition (Australian study published in America?) – Link)). All of these trials had less than 100 patients and some significant weaknesses.

Emedicine, however, states that patients with iron deficiency are asymptomatic – Link – (I couldn’t find a link to a reference though?)

Aside from fatigue, addressing depression risk, a larger study (MMPI) in Behavioural Medicine 1999 looked at 365 women who were iron deficient and found no link between iron deficiency and depression – Link

Question 2 – What about in children and pregnant women?

In CHILDREN there is good evidence to show decreased neurocognitive development, immune status, and exercise tolerance in children (WHO – see below).

In PREGNANCY decreased iron levels have been associated with increased perinatal risks increased perinatal mortality. This is summarised and discussed in chapter 3 of WHO document on iron deficiency 2001 – Link  – (Australian Women’s hospital guidelines suggest screening with a ferritin at booking in blood tests – Link)

For adults it is a little unclear. It would seem a group of small trials suggest improvement in fatigue, and perhaps, neurocognition with iron replacement in iron deficiency without anaemia – but obviously more research is required.

Question 3 – How do I interpret iron studies?

Here is where things can go pear shaped.

Firstly, samples should be done fasting in the morning to give more accurate and repeatable results (GESA & MJA) – Link

I love a good flow chart. Here is a great guide with on how to evaulate the patient with suspected iron deficiency in MJA Clinical Update 2010. Check out box 3 at the bottom – Link (This is our “Glancing Resource” of this Map)

Gastroenterological Society of Australia (GESA) 2011 describes the interpretation of iron studies as: “Serum ferritin concentration is the single most specific biochemical test that correlates with relative total body iron stores. Reduced ferritin is the most useful indicator of iron deficiency as there is no other condition that can produce this result.” They have a great summary article located here – Link

So step one. Does the patient have low ferritin (e.g. iron stores). If they are low, then the patient is iron deficient. End of discussion.

But, ferritin can go up in inflammation?

Question 4 – What do you do if the patient has an inflammatory condition and suspect they are iron deficient?

The Journal of Family Practice (2010) discusses evaluation of IDA in chronic inflammation and concludes that there is no good guidelines for diagnosis of IDA in chronic inflammation though marked the soluble transferrin receptor plasma level as a possible future tool – Link – Bone marrow sampling is recommended, but having seen bone marrows done (ouch…) this does seem a little extreme.

Question 5 – What is the soluble transferrin receptor plasma level?

The theory is that in iron defiency “…soluble transferrin receptor levels in plasma are elevated if there is increased iron demand due to iron deficiency (RCPA)” – Link. The Journal of Gastrointestinal Liver Disease 2009 discusses the use of soluble transferrin receptor levels in evaluation of iron deficiency further – Link

GESA’s stance is “…iron studies may be difficult to interpret in the presence of an elevated ferritin, and more specialised tests such as red cell protoporphyrin, transferrin binding receptors or even bone marrow biopsy may be required to distinguish between iron deficiency and anaemia of chronic disease” – Link

Question 6 – Can I use serum iron to diagnose iron deficiency? (My pet hate…)

Perthhaematology describes the use of serum iron as a measure of iron deficiency – “Serum iron is virtually useless in assessing iron stores” – Link

Lets just say it again. Labtests online explains – “The serum iron level varies markedly throughout the day and according to recent intake, It is not helpful and should not be used as a stand-alone test in the diagnosis of iron deficiency anaemia.” – Link

Question 7 – What about that “anaemia of chronic disease” thing?

Here is a good brief ‘back to basics’ guide on the pathophysiology of anaemia of chronic disease (ACD) on the ‘Pathology Student’ with a rather challenging slogan – Link

“The prevailing opinion is that anemia of chronic disease is an adverse consequence of systemic illness… despite management guidelines, anemia of chronic disease remains underrecognized and undertreated…. We do not believe there is sufficient evidence to support such a conclusion.” Here is a thought provoking and challenging article in Canadian Medical Associations Journal 2008 entitled – “Anemia of chronic disease: A harmful disorder or an adaptive, beneficial response?” – Link

For a more practical guide on how to diagnose and what is standard practice to do with a patient with anaemia of chronic disease we turn to Hematology American Society of Hematology Education Program 2010 – Link

Question 8 – What are the most common causes of iron deficiency and the ‘red flags’?

The best article to address this question has already been quoted above. If you haven’t yet looked at the MJA 2010 clinical update then you should! – Link

For a second opinion there is an article in Gut 2011 on management of IDA (British based) – Link

Question 9 – How do I treat iron deficiency?

A great article from the NPS talks about iron deficiency and then goes on to address the different options available in the Australian market (2010). Great stuff and very clinically useful! – Link

I think it is very important here in Australian General Practice to also mention that in Aboriginal and Torres Strait Islander populations iron deficiency is endemic – particularly in kids. It’s important to know the current guidelines on this potentially reversible issue. RACGP guidelines – Link

RCH has some great clinical guidelines and advice for replacing iron stores in children – Link

The question I have is does liquid iron actually improve gastric symptoms of taking iron supplements? Nope I can’t find any evidence of this BUT I did learn that liquid iron should be taken through a straw and diluted with water or juice to avoid the persons teeth! Can cause temporary staining otherwise! Not great resource but easy to read – Livestrong – Link

Question 10 – What can I recommend dietary wise to my vegetarian young women?

Here is a good link from myDr (by MIMS) of patient information on increasing dietary iron in a vegetarian diet – Link

Australian Doctor 2012 challenges the view that vegetarians are necessarily at increased risk of iron deficiency anyway from an article in MJA supplement! – Link

Conclusion

So after having pumped some iron I am off to have some spinach with Olive Oyl!

Cheers everyone! Rob.

PS. Don’t diagnose iron deficiency on SERUM IRON!