Investigation and management of a raised serum ferritin

Abstract

Serum ferritin level is one of the most commonly requested investigations in both primary and secondary care. Whilst low serum ferritin levels invariably indicate reduced iron stores, raised serum ferritin levels can be due to multiple different aetiologies, including iron overload, inflammation, liver or renal disease, malignancy, and the recently described metabolic syndrome. A key test in the further investigation of an unexpected raised serum ferritin is the serum transferrin saturation. This guideline reviews the investigation and management of a raised serum ferritin level. The investigation and management of genetic haemochromatosis is not dealt with however and is the subject of a separate guideline.

Reference intervals established using indirect method for serum ferritin assayed on Abbott Architect i2000SR analyzer in Chinese adults

“…To gain insight into the effect of age on SF levels, we further tested whether there was a significant difference between various age‐specific subgroups by Z test and found that the SF levels in females aged ≥50 years were significantly higher than those in those aged <50 years. These findings are in good agreement with those by Ogilvie et al and Adams et al Indeed, SF values in adult females start to rise after 50 years of age as a result of iron loss from menstruation and pregnancies . In view of this, it is necessary to establish the sex‐ and age‐specific RIs for SF in our own laboratory.…”

“…Nevertheless, the RIs for most analytes are to some degree method‐ and instrument‐dependent . In addition, differences between populations are also an issue and can reduce the validity of RIs . For example, it was reported that one method can give 1.63 times higher values than the other method for SF; mean SF values are found to be higher at all ages in adult black males than in adult white males .…”

“…Ferritin, a soluble 450 kDa protein, is a major iron storage protein presenting in the intracellular compartments . As the most abundant transition metal element in the body, iron is widely involved in various physiological processes such as oxygen transport, electron transport, cell cycle regulation, energy metabolism, and DNA synthesis .…”

“…Nevertheless, although measurement of SF has largely replaced laboratory assays of serum iron and transferrin or total iron‐binding capacity in clinical practice, there is no gold‐standard method for measuring SF. At present, SF can be measured using immunoassays, for example, enzyme‐linked immunosorbent assay (ELISA), electrochemiluminescent immunoassay (ECLIA), chemiluminescent immunoassay (CLIA), or immunoturbidometric assay . Because of diversity and heterogeneity of ferritin antigens, and issues related to the reagent design in different assay methods, the RIs or normal ranges for SF in individuals vary depending on the assay method used .…”

“…This makes it difficult for physicians to interpret the measurement results. In addition, studies have addressed there are significant ethnic‐specific differences in SF levels . Hence, it is necessary to establish their own RIs for use in clinical laboratories with their population and analytical methods…”