From the Guidelines
High ferritin levels with low iron stores, also known as iron deficiency anemia with elevated ferritin, require a comprehensive approach to address both the iron deficiency and the underlying cause of elevated ferritin. This condition can be confusing since ferritin typically reflects iron storage, but it is an acute phase reactant that increases during inflammation, infection, liver disease, or malignancy, masking underlying iron deficiency 1. The diagnosis of iron deficiency in this context is complicated by the fact that ferritin levels can be elevated due to inflammation, making it essential to assess other parameters such as transferrin saturation, total iron binding capacity, C-reactive protein, and liver function tests to determine the underlying cause of the discrepancy 1. Some key points to consider in the diagnosis and management of this condition include:
- The lower limit of ferritin consistent with normal iron stores should be increased to 100 μg/L in the presence of biochemical evidence of inflammation 1.
- A transferrin saturation level below 16% is a sensitive marker of iron deficiency, but it has a low specificity of only 40–50% 1.
- Measurements of inflammatory parameters that are independent of iron metabolism, such as ESR and CRP, should be carried out to aid diagnosis 1.
- Treatment involves addressing both the iron deficiency and the underlying cause of elevated ferritin, and may include oral iron supplementation, intravenous iron formulations, and treatment of the underlying inflammatory condition 1. The most appropriate initial treatment for high ferritin levels with low iron stores is oral iron supplementation, such as ferrous sulfate 325mg once or twice daily, taken on an empty stomach with vitamin C to enhance absorption. If oral supplementation is not tolerated or effective, intravenous iron formulations like iron sucrose or ferric carboxymaltose may be necessary 1. It is crucial to investigate the cause of this discrepancy through additional testing and to treat the underlying inflammatory condition to resolve both the iron deficiency and normalize ferritin levels 1.
From the Research
High Ferritin Low Iron Stores
- High ferritin levels can be associated with low iron stores, particularly in patients with chronic kidney disease (CKD) or anemia of chronic disease 2, 3.
- In CKD patients, ferritin levels between 200 and 1,200 ng/mL may be related to inflammation, latent infections, malignancies, or liver disease, rather than iron deficiency 2.
- Iron deficiency can be masked by high ferritin levels, and traditional iron markers such as serum ferritin and transferrin saturation ratio (TSAT) may be confounded by non-iron-related conditions 2, 4.
- High serum ferritin but low iron, TSAT levels are associated with increased mortality, whereas hemoglobin exhibits a U-shaped risk for death 2.
Diagnosis and Treatment
- Diagnosis of iron deficiency in patients with high ferritin levels requires careful evaluation of iron markers, including serum ferritin, TSAT, and soluble transferrin receptor (sTfR) 5, 3.
- Treatment of iron deficiency in patients with high ferritin levels may involve intravenous iron supplementation, which can decrease hemoglobin variability and ESA hyporesponsiveness 2, 6.
- Erythropoiesis-stimulating agents (ESAs) may be used in combination with intravenous iron to correct anemia in patients with CKD or chronic obstructive pulmonary disease (COPD) 5, 6.
Prevalence and Effects
- Iron deficiency is common in patients with COPD, but is rarely investigated or treated 6.
- Correction of iron deficiency in COPD patients with ESAs and intravenous iron can improve anemia, iron deficiency, and dyspnea 6.
- High ferritin levels can be associated with increased mortality, particularly in patients with CKD or anemia of chronic disease 2, 4.