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My name is Fernando Florido (also known as Juan Fernando Florido Santana), a GP in the UK. In this episode, I will go through the guideline by the British Society for Haematology on the laboratory diagnosis of functional iron deficiency, focusing on what is relevant in Primary Care only.

In the last episode I covered:

·      The guideline by the British Society for Haematology on the laboratory diagnosis of iron deficiency

In the next episode, I will cover:

·      The assessment of raised ferritin

I am not giving medical advice; this video is intended for health care professionals, it is only my summary and my interpretation of the guidelines and you must use your clinical judgement.  

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The link to the new guideline by the British Society for Haematology on the laboratory diagnosis of functional iron deficiency can be found here:

·      https://onlinelibrary.wiley.com/doi/10.1111/bjh.12311

The link for the British Society for Haematology website can be found here

·      https://b-s-h.org.uk/

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Transcript

If you are listening to this podcast on YouTube, for a better experience, switch to the video version. The link is in the top right corner of the video and in the episode description.

Hello and welcome, I am Fernando, a GP in the UK. Today, we will go through the guideline by the British Society for Haematology on the laboratory diagnosis of functional iron deficiency, focusing on what is relevant in Primary Care only. A link to it is in the episode description.

If you haven’t already, I recommend that you check out the last episode where I covered the laboratory diagnosis of iron deficiency

And in the next episode, I will cover the assessment of raised ferritin. So, stay tuned for that!

Right, let’s jump into it.

Whilst the concept of functional iron deficiency—or FID—is both important and very relevant to us in Primary Care, reading the full guideline can be overwhelming. It’s full of detailed considerations more relevant to specialists and secondary care. So, instead of summarising that in its entirety, I’m just going to give you a general overview. I’ll take you through the relevant investigations, explaining each one in plain terms, and linking it back to what we need to know and do in general practice.

And first of all, what is Functional Iron Deficiency (FID)?

Functional Iron Deficiency happens when the body has enough iron stored, but can’t get it to where it’s needed — particularly, the bone marrow where red blood cells are made. This is different from true iron deficiency, but the effect is similar: not enough haemoglobin is made, leading to anaemia.

Why Does This Happen?

FID is common in long-term illnesses, like:

• Chronic inflammation (e.g. rheumatoid arthritis)
• Infections
• Cancer and
• Chronic kidney disease (CKD)

In these situations:

• The liver produces hepcidin, a hormone that blocks iron release from stores and reduces absorption from the gut.
• So, even if ferritin looks normal or high, the bone marrow can’t access the iron, so red cell production is reduced.

What Should GPs Know about functional iron deficiency?

Let’s look at a very simplified version of the Pathophysiology. And that is that

• Chronic Inflammation leads to→ ↑a rise in Hepcidin → ↓which reduces Iron transport → which in turn leads iron not reaching the Bone.
• This results in anaemia of chronic disease.
• FID can also happen when bone marrow is overstimulated (e.g., from treatment with ESA in CKD), using iron faster than it can be delivered.

When should we Suspect FID? We should suspect it clinically if there is anaemia in chronic disease (especially if it is not improving with oral iron). We should also suspect it depending on test results. And let’s now look at the list of possible tests that can be requested for functional iron deficiency, starting with the ones that we can order in Primary Care:

·      Firstly, we have MCV or Mean cell Volume and MCH or Mean Cell Haemoglobin. They tell us the average size of red blood cells and the average amount of haemoglobin in each red cell respectively.

They are useful at the time of diagnosis and for tracking trends over weeks or months. However, they don’t change quickly, so they not suitable for identifying rapid changes.

·      Then we have serum Ferritin. This one we all know well. It reflects the amount of stored iron in the body. If it’s under 15 micrograms per litre, that strongly indicates true iron deficiency. Ferritin is an acute phase reactant—it rises in inflammation and chronic disease. So, a high ferritin doesn’t exclude FID. In CKD patients, a ferritin under 100, or sometimes even 200 increases the likelihood of requiring further iron treatment. In CKD, values as high as 1200 may still be consistent with iron-restricted anaemia. But we should not use ferritin alone to guide treatment but consider it in the context of other tests too.

·      Then we have Transferrin Saturation – or TSAT which shows the percentage of transferrin that is actually carrying iron. Alone, it’s not a reliable guide for iron therapy in CKD patients but combined with ferritin and other tests it can help diagnose FID or monitor treatment. Transferrin saturation can also be influenced by inflammation, so it’s not a standalone tool.

·      Now let’s move onto more specialist markers of iron status, especially for functional iron deficiency, like %HRC – Percentage of Hypochromic Red Cells, which measures the proportion of red cells that contain less haemoglobin than they should. It’s actually the best-established lab test for detecting FID.

·      Then we have CHr – Reticulocyte Haemoglobin Content, which measures how much haemoglobin is in reticulocytes. It’s the second most established marker for FID and a value of less than 29 picograms suggests functional iron deficiency.

·      There are other truly specialist tests, which are:

o  Zinc Protoporphyrin

o  Bone Marrow Examination

o  sTfR – Soluble Transferrin Receptor

o  Serum Erythropoietin and

o  Hepcidin, which we mentioned earlier and which plays a role in the pathophysiology of functional iron deficiency

What is the typical picture of anaemia in FID?

Well, haemoglobin is usually low or normal, often showing a normocytic normochromic picture.

Ferritin will be normal or high Because being an acute-phase reactant, it’s falsely elevated in inflammation

Transferrin saturation is usually low <20% despite the high ferritin. Transferrin saturation is reduced because of iron being unavailable.

Serum iron is low, both in true iron deficiency and functional iron deficiency. However, TIBC is normal or low, whereas it would be high in true iron deficiency

ESR or CRP tend to be high in functional iron deficiency reflecting underlying inflammation and finally functional iron deficiency also show that

Reticulocyte Hb content is low and percentage of hypochromic cells are high

When should we refer to Secondary Care?

We should consider referral if:

·      There is persistent or unexplained anaemia, and we suspect FID and when oral iron hasn’t worked.

·      If The patient is on (or might need) IV iron or erythropoiesis-stimulating agents (ESAs) which are managed in secondary care.

·      If There is diagnostic uncertainty like for example mixed deficiencies, or a high ferritin but the picture still points to iron deficiency anaemia or

·      If there is anaemia in CKD stages 4–5, active cancer, or complex comorbidities

And to end, let’s remember that our role in Primary Care is:

• To Recognise the FID pattern: that is, chronic disease + anaemia + and a ferritin which is not low
• To exclude other causes, for example bleeding, B12/folate deficiency, chronic kidney disease etc.
• To manage oral iron therapy and initial assessment remembering that
• We should not overlook anaemia in patients with chronic disease. FID is treatable but IV iron and ESA are specialist decisions.

So that is it, a review of the laboratory investigations of functional iron deficiency.

We have come to the end of this episode. Remember that this is not medical advice but only my summary and my interpretation of the guidelines. You must always use your clinical judgement.

Thank you for listening and goodbye.