Functional vs Absolute Iron Deficiency Interpreter
Functional vs Absolute Iron Deficiency Interpreter
Distinguish empty iron stores from iron that is present but locked away, using ferritin, transferrin saturation and CRP.
Functional vs Absolute Iron Deficiency
Ferritin + TSAT + CRPFerritin 240 µg/L, TSAT 14%, CRP 22 mg/L
The distinction
Functional — stores adequate, supply blocked: ferritin normal or high, TSAT low
- hepcidin
- the mechanism of functional deficiency — inflammation raises it, and it blocks both gut absorption and macrophage iron release
- TSAT < 20%
- restricted iron supply, whatever the store size
- CRP > 5 mg/L
- raises the ferritin threshold from 30 to 100 µg/L
Worked example
Ferritin 240 µg/L, TSAT 14%, CRP 22 mg/L
Ferritin above 100 → stores are not empty
TSAT 14% → supply to the marrow is restricted
→ functional iron deficiency; oral iron will not be absorbed
Patterns compared
| Absolute | Functional | Anaemia of inflammation | |
|---|---|---|---|
| Ferritin | Low | Normal or high | High |
| TSAT | Low | Low | Low |
| CRP | Any | Usually raised | Raised |
| sTfR | High | Normal or high | Normal |
| Responds to oral iron | Yes | No | No |
| Responds to IV iron | Yes | Often | Rarely |
Why the distinction changes treatment
Absolute iron deficiency means the body has run out of iron. Functional iron deficiency means it has iron but cannot get at it — hepcidin, driven up by inflammation, degrades ferroportin and traps iron inside macrophages and enterocytes while the erythroid marrow goes short.
Treatment diverges sharply. Absolute deficiency responds to oral iron, provided absorption is intact. Functional deficiency does not, because the same hepcidin that sequesters stored iron also blocks absorption from the gut — prescribing oral iron produces side effects without benefit. Intravenous iron bypasses the absorptive block and does help in selected patients, notably in heart failure and chronic kidney disease, where trials have shown symptomatic benefit even with ferritin well inside the normal range.
The two also coexist. A patient with inflammatory bowel disease can be inflamed and bleeding at once, and the pattern then shows features of both. Where ferritin and saturation give an ambiguous answer, soluble transferrin receptor or the sTfR-ferritin index is the tiebreaker, because neither is distorted by the acute-phase response.
Frequently asked questions
What is functional iron deficiency?
Iron stores are adequate but the iron cannot reach the marrow, because inflammation-driven hepcidin traps it in macrophages. Ferritin is normal or high while transferrin saturation is low.
Why does oral iron not work in functional deficiency?
The same hepcidin that sequesters stored iron also degrades ferroportin in the gut, blocking absorption. Oral iron produces gastrointestinal side effects without raising haemoglobin.
Should functional iron deficiency be treated at all?
In some settings, yes. Intravenous iron improves symptoms and exercise capacity in heart failure with a ferritin below 100 µg/L, or 100 to 300 µg/L with a saturation under 20%, and is standard in chronic kidney disease on erythropoiesis-stimulating agents.
Which test settles an ambiguous case?
Soluble transferrin receptor, or the sTfR-ferritin index. Neither is affected by inflammation, so both remain interpretable when ferritin cannot be trusted.
Related calculators
References
- Weiss G, Ganz T, Goodnough LT. Anemia of inflammation. Blood. 2019;133(1):40–50.
- Ponikowski P et al. Beneficial effects of long-term intravenous iron therapy in heart failure. Eur Heart J.
- KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease.