From the Guidelines
If ferritin levels are within normal limits (WNL), it generally indicates that iron deficiency is not present, but in cases of inflammation or chronic disease, a serum ferritin up to 100 mg/L may still be consistent with iron deficiency. Ferritin is the primary storage protein for iron in the body and serves as one of the most sensitive indicators of iron status, as noted in the British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults 1. When iron stores become depleted, ferritin levels fall before other markers of iron deficiency appear, such as decreased hemoglobin or microcytic anemia. This makes ferritin an excellent early indicator of iron deficiency. However, it's essential to consider that ferritin is also an acute phase reactant, meaning its levels can be falsely elevated during inflammation, infection, liver disease, or malignancy, as highlighted in the ESPEN guideline on clinical nutrition in inflammatory bowel disease 1. In these situations, a person might have normal or even elevated ferritin levels despite having true iron deficiency.
Some key points to consider in the diagnosis of iron deficiency include:
- Serum ferritin is the single most useful marker of iron deficiency anaemia, but other blood tests, such as transferrin saturation, can be helpful if a false-normal ferritin is suspected 1.
- In the presence of inflammation, a serum ferritin up to 100 mg/L may still be consistent with iron deficiency, and a combination of true iron deficiency and anemia of chronic disease is likely if the serum ferritin level is between 30 and 100 mg/L 1.
- A good response to iron therapy, such as a hemoglobin rise ≥10 g/L within a 2-week timeframe, in anaemic patients is highly suggestive of absolute iron deficiency, even if the results of iron studies are equivocal 1.
For most patients without inflammatory conditions, a normal ferritin level reliably excludes iron deficiency as a diagnosis. However, if iron deficiency is strongly suspected despite normal ferritin, additional tests may be helpful, including transferrin saturation, serum iron, total iron binding capacity, or soluble transferrin receptor. It's crucial to interpret ferritin levels in the context of the patient's overall clinical picture, considering factors such as inflammation, chronic disease, and other potential causes of elevated ferritin levels.
From the Research
Iron Deficiency Diagnosis
- Ferritin is an iron storage protein and its concentration in the plasma or serum reflects iron stores; low ferritin indicates iron deficiency, while elevated ferritin reflects risk of iron overload 2.
- However, ferritin is also an acute-phase protein and its levels are elevated in inflammation and infection, complicating the diagnosis of iron deficiency 2, 3.
- A serum ferritin threshold of <100 μg/L or transferrin saturation (TSAT) < 20% can be considered diagnostic for iron deficiency in patients with inflammatory conditions such as chronic heart failure, chronic kidney disease, and inflammatory bowel disease 3.
Ferritin Levels and Iron Deficiency
- If serum ferritin is within normal limits (WNL), it does not necessarily rule out iron deficiency, especially in patients with inflammatory conditions 3.
- In such cases, TSAT and other markers of iron availability should also be assessed to confirm iron deficiency 3, 4.
- The soluble transferrin receptor (sTfR) and sTfR/log ferritin index can also be useful in diagnosing iron deficiency anemia, especially in patients with ferritin levels in the grey zone (10-100 ng/ml) 5.
Diagnostic Thresholds
- The standard threshold for iron deficiency is <30 μg/L, but this may not apply in patients with inflammatory conditions 2, 3.
- A threshold of <100 μg/L or TSAT < 20% can be considered diagnostic for iron deficiency in certain patient populations 3.
- The use of transferrin saturation as a diagnostic criterion for iron deficiency can be beneficial, especially in patients with chronic inflammatory diseases 4.