From the Guidelines
High ferritin levels with low iron levels, also known as ferritin high ring low, can indicate a condition called anemia of chronic disease or iron sequestration, and the most appropriate course of action is to identify and treat the underlying cause rather than simply supplementing with iron, as stated in the expert consensus guidelines 1. To address this condition, it's essential to understand that ferritin synthesis is dependent on cellular iron, and even during states of inflammation where absolute iron deficiency is present, the rise in ferritin is blunted 1. Some key points to consider in the diagnosis and management of this condition include:
- The frequency of administration and duration of benefit of intravenous iron is dependent on the underlying etiology of the iron deficiency, and laboratory evaluation following IV iron should include a CBC and iron parameters (ferritin, percent transferrin saturation) 4 to 8 weeks after the last infusion 1.
- In the absence of inflammation, the goal ferritin is 50 ng/mL, regardless of sex at birth, and a TSAT <20% has high sensitivity for diagnosing absolute or functional iron deficiency 1.
- Soluble transferrin receptor (sTfR) has been shown to be more sensitive in patients with inflammatory conditions where the ferritin (but not the TSAT) is unreliable for evaluation of iron deficiency and iron deficiency anemia, and reticulocyte Hb content is a direct assessment of the functional availability of iron to the erythropoietic tissue 1.
- The diagnosis of iron deficiency may also be complicated by the fact that iron deficiency and the anemia of chronic disease frequently coexist and interact in a complex manner, so that a reliable differentiation using laboratory methods may be impossible, and a combination of parameters should be assessed to determine the exact type of anemia in any specific clinical scenario 1. A comprehensive evaluation by a healthcare provider is necessary to develop an appropriate treatment plan based on the specific cause of the ferritin-iron imbalance, and patients should avoid self-supplementing with iron as this could worsen certain conditions like hemochromatosis 1.
From the Research
Ferritin Levels and Iron Status
- High ferritin levels can indicate iron overload, but they can also be elevated due to inflammation and infection 2, 3, 4
- Low ferritin levels are highly specific for iron deficiency 2, 3
- The optimal serum ferritin level range is suggested to be between 20 and 100 ng/mL, with transferrin levels between 20 and 50% 5
Diagnostic Accuracy of Ferritin
- Ferritin has a high sensitivity and specificity for diagnosing iron deficiency in people presenting for medical care, but the evidence is low-certainty 2
- The diagnostic accuracy of ferritin for iron overload is very low-certainty, and it is not recommended as a sole diagnostic test 2
- Hyperferritinemia is a non-specific finding and can be caused by various conditions, including inflammation and infection 3, 4
Clinical Implications
- Elevated ferritin levels are linked to various diseases, including coronary artery disease, malignancy, and poor outcomes following stem cell transplantation 6
- Hyperferritinemia is a key acute-phase reactant and can be used as an indication for therapeutic intervention to control inflammation in high-risk patients 4
- Further investigation is needed to understand the role of ferritin in uncontrolled inflammatory conditions, both as a biomarker and mediator of disease 4