Serum ferritin (SF)


Ferritin is 24-subunit iron storage molecule that forms a hollow sphere with a capacity to hold up to 4000 iron atoms.1 Stored iron is predominantly held in reticuloendothelial cells (macrophages) and hepatocytes, but ferritin is in fact produced in many of the body’s cells, and a proportion of this is secreted into the plasma.2 Accordingly, plasma ferritin accounts for only a proportion of total body ferritin, and in thalassemia patients serum ferritin has been shown to correlate with the volume of transfused blood.2

However, the secretion of ferritin into the plasma can be mediated by a number of other factors. This means that the measurement of serum ferritin may be confounded in a number of important clinical contexts. Ascorbate deficiency and hypothyroidism reduce serum ferritin.2 Conversely, chronic inflammatory conditions, increased erythropoietin levels, hematological malignancies, liver damage, pancreatic cancer and acute inflammation may all increase serum ferritin.2 More recently, it has been proposed that ferritin may be a mediator of the inflammatory response, not merely a marker.3


Serum ferritin measurement is inexpensive and available in many hospital laboratories. Serum ferritin facilitates regular monitoring.

Comparisons of serum ferritin to liver iron stores have confirmed the correlation. When serum ferritin was compared to liver iron concentration (LIC, as measured through liver biopsy) for patients with thalassemia major, the serum ferritin level correlated positively (r = 0.73, p < 0.005).4 An alternative approach quantifying liver iron via magnetic resonance imaging has shown that serum ferritin correlates well in patients with transfusional iron overload and thalassemia major (r = 0.76, p < 0.001) and sickle cell anemia (r = 0.75, p < 0.001).5 However the same study highlighted that serum ferritin as a single measurement can be erratic due to its mediation by other physiological processes.

The relationship however is slightly less straight-forward in the context of non-transfusional iron overload. Serum ferritin levels in patients with thalassemia intermedia are significantly lower for a given liver iron concentration than in thalassemia major patients.6 Accordingly, serum ferritin levels may under-estimate the degree of bodily iron in non-transfusion-dependent thalassemia (NTDT) patients:7 such patients may require more direct approaches to iron measurement.

In patients with sickle cell disease the relationship between serum ferritin and liver iron concentration can be non-linear, especially in the range of 1500-3000  μg/L.8

Indicative serum ferritin levels in the context of iron overload, based on evidence in thalassemia major patients as described later

Normal ferritin <300 μg/L
Mild to moderate iron overload >1000 ≤ 2500 μg/L
Severe iron overload > 2500 μg/L

Most guidelines recommend serial serum ferritin measurement every 1-3 months, although this can be adapted to individual patient needs.9-12

Chelation Thresholds


In transfusion-dependent thalassemia (TDT), a serum ferritin level consistently > 2,500 μg/L has been shown to increase the risk of cardiac complications and endocrine disease.13,14 While maintaining levels <1000 μg/L is associated with increased survival and less morbidity.14,15 Current practice is to initiate iron chelation therapy when the serum ferritin rises above 1000 μg/L.10

In non-transfusion dependent thalassemia (NTDT) levels > 800 μg/L were associated with increased morbidity in cross-sectional and long-term studies,16 the current recommendation is to initiate chelation therapy beyond this threshold.11

Sickle Cell Disease

Serum ferritin values higher than 3,000 were associated with liver fibrosis in SCD patients while values <1,500 μg/L indicated absence of such effects.8 The recommendation is to start chelation in patients who show levels >1,000 μg/L.17

Myelodysplastic Syndromes

Serum ferritin levels higher than 1,000 μg/L have been associated with decreased survival and increased risk of leukemic transformation in MDS patients.18 Several guidelines for MDS management thus recommend starting iron chelation therapy when serum ferritin levels reach values of >1,000 μg/L.12,19

Next: Transferrin


Iron Chelation Therapy in Thalassemia Find out more…

Sickle Cell Disease

Iron Chelation Therapy in Sickle Cell Find out more…

Myelodysplastic Syndromes

Iron Chelation Therapy in MDS Find out more...


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