Ferritin low in deficiency, normal or high in chronic disease
Mnemonic
“Deficiency makes more lorries and carries less cargo”:
- Iron deficiency: low ferritin, low iron, high transferrin and TIBC, low saturation
- Anaemia of chronic disease: normal or high ferritin, low iron, low TIBC, low saturation
The distinction follows from hepcidin, which in inflammation locks iron into stores, so the stores are full but the iron is unavailable.
“Ferritin is an acute phase reactant” is the caveat that matters most: a normal ferritin does not exclude iron deficiency when there is inflammation, and a threshold of under 15 confirms deficiency while over 100 with a normal CRP makes it unlikely.
Haemochromatosis is the mirror image: high iron, high ferritin, high saturation over 45 per cent, low TIBC.
Iron deficiency is a symptom, not a diagnosis: in men and postmenopausal women it requires investigation of the gastrointestinal tract and coeliac serology.
Expansion
| Test | Iron deficiency | Anaemia of chronic disease | Iron overload |
|---|---|---|---|
| Serum iron | Low | Low | High |
| Ferritin | Low | Normal or high | High |
| Transferrin / TIBC | High | Low | Low |
| Transferrin saturation | Low | Low or normal | High |
The pattern is driven by hepcidin: it is suppressed in iron deficiency, allowing absorption and release, and raised by inflammation, trapping iron in macrophages so that serum iron falls despite adequate stores.
Pitfalls
- Ferritin is an acute phase protein, rising in infection, inflammation, malignancy and liver disease, so it can be normal in a genuinely iron-deficient patient. A threshold of 100 rather than 15 is used where inflammation is present
- Transferrin saturation is more reliable in that setting
- Combined deficiency and chronic disease is common
In an adult, unexplained iron deficiency anaemia requires investigation of the gastrointestinal tract for occult blood loss, since it is a presenting feature of colorectal carcinoma.