top of page

Interpreting the grey zone Ferritin: When Is Iron Deficiency Likely?

  • Jun 15
  • 3 min read

Ferritin remains the single most useful laboratory marker for assessing iron stores and is recommended by major international guidelines as the first-line test when iron deficiency is suspected.



Ferritin <30 μg/L

Iron deficiency is highly likely.

In most clinical situations, a ferritin below 30 μg/L is considered diagnostic of iron deficiency.


Ferritin 30–100 μg/L

This is the grey zone.

Iron deficiency may still be present, particularly when:

  • Inflammation is present

  • Obesity is present

  • MASLD is present

  • Chronic kidney disease is present

  • Chronic disease is present


Ferritin >100 μg/L

Iron deficiency becomes increasingly unlikely, but still possible.

Alternative explanations should be considered, particularly:

  • Inflammation

  • Obesity

  • MASLD

  • Chronic kidney disease

  • Infection

  • Malignancy


Ferritin >300 μg/L

Absolute iron deficiency is very uncommon. Interpretation should focus on the broader clinical picture and consideration of alternative diagnoses.


Specialist Insight

The challenge is rarely diagnosing iron deficiency when ferritin is very low.

The challenge is recognising iron deficiency when ferritin appears "normal."

What Should I Do When Ferritin Is Borderline?

A ferritin of 30–100 μg/L can be difficult to interpret.

Additional tests may be helpful when clinical suspicion remains high.


Consider

  • CRP

  • Transferrin saturation (TSAT)

  • Ret-He


Typical Findings Suggesting Iron Deficiency

  • Low MCV

  • Low TSAT

  • Low Ret-He (<25)

  • Elevated CRP with apparently normal ferritin


Clinical Pearl

Inflammation can make ferritin look reassuring when iron stores are actually depleted.


When Should I Consider Ret-He?

Reticulocyte haemoglobin equivalent (Ret-He) is available in New Zealand laboratories.

Ret‑He measures the haemoglobin content of newly released red cells, giving a real‑time indication of whether the bone marrow has enough iron to make healthy erythrocytes. It’s an early, sensitive marker of iron‑restricted erythropoiesis and is particularly useful when ferritin is unreliable due to inflammation.



Ret-He may be particularly useful when:

  • Ferritin is between 30–100 μg/L

  • Chronic inflammation is present

  • Chronic kidney disease is present

  • Functional iron deficiency is suspected

  • The diagnosis remains uncertain


Why Is Ret-He Helpful?

Ferritin reflects stored iron.

Ret-He reflects iron available for erythropoiesis.

These are not the same thing.


Ret-He

>30 pg Usually adequate iron availability

28–30 pg Borderline (Interpret alongside ferritin, TSAT and clinical context)

<28 pg Suggestive of iron-restricted erythropoiesis

<25 pg Strongly suggestive of iron deficiency


Specialist Insight

Ret-He is often most useful when ferritin interpretation becomes difficult. Ret‑He is automatically reported whenever a reticulocyte count is requested, so asking for a retic count will usually generate Ret‑He alongside it.


When Is Iron Deficiency Unlikely?

Iron deficiency becomes increasingly unlikely when:

  • Ferritin is well above 100 μg/L

  • TSAT is normal

  • Ret-He is normal

  • There is no convincing clinical context

At this point, alternative causes of anaemia should be considered.


Common Alternatives

  • Anaemia of chronic inflammation

  • Chronic kidney disease

  • Haemoglobinopathies

  • Bone marrow disorders

  • Vitamin B12 deficiency

  • Folate deficiency

What About Soluble Transferrin Receptor?

Historically, soluble transferrin receptor (sTfR) was promoted as a useful marker of iron deficiency because it is less affected by inflammation than ferritin. While physiologically attractive, its use in routine clinical practice has been limited by:

  • Variable availability

  • Higher cost

  • Inter-assay variability

  • Longer turnaround times

  • Limited familiarity among clinicians


Compared with sTfR, Ret-He is:

  • Available on many modern haematology analysers

  • Rapid and inexpensive

  • Easy to incorporate into routine full blood count analysis

  • Useful in both absolute and functional iron deficiency


Specialist Insight

Ret-He is increasingly preferred in routine clinical practice because of practicality and availability rather than a clear superiority in diagnostic accuracy.


Five Things To Remember

  1. A low ferritin confirms iron deficiency; a normal ferritin may not exclude it.

  2. Ferritin between 30–100 μg/L often requires clinical interpretation if iron deficiency is still suspected.

  3. Inflammation, obesity, MASLD and chronic disease may elevate ferritin and mask deficiency.

  4. Ret-He reflects iron available for erythropoiesis and may be useful when ferritin is borderline or difficult to interpret.

  5. Ferritin tells you about iron stores; Ret-He tells you about iron delivery.


Useful Resources

Disclaimer

This resource is intended for healthcare professionals and reflects available evidence at the time of publication. Clinical decisions should be individualised according to patient circumstances, local referral pathways, and specialist advice where appropriate.

 
 
 

Comments


bottom of page