From the Guidelines
To determine if high ferritin is an acute phase reactant, look for concurrent inflammatory conditions and check for elevated inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as the pattern of other iron studies, including transferrin saturation and serum iron levels. According to the most recent guidelines 1, 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. In cases where the transferrin saturation (TSAT) and ferritin present a discordant depiction of iron status, a TSAT <20% has high sensitivity for diagnosing absolute or functional iron deficiency, but a ferritin of <100 ng/mL has a low sensitivity of 35%–48% 1.
The presence of inflammation can be assessed by measuring inflammatory parameters that are independent of iron metabolism, such as ESR and CRP 1. In the presence of biochemical evidence of inflammation, the lower limit of ferritin consistent with normal iron stores should be increased to 100 μg/L, and hypoferraemia should be considered likely if TSAT is below 16% and serum ferritin is between 30 and 100 g/L 1.
Some key points to consider when evaluating high ferritin levels include:
- The timing of ferritin elevation, with sudden increases during illness suggesting an acute phase response
- The pattern of other iron studies, including transferrin saturation and serum iron levels
- The presence of concurrent inflammatory conditions or recent infections
- The use of additional tests, such as soluble transferrin receptor (sTfR) or reticulocyte hemoglobin content (CHr), to help differentiate between iron deficiency and anemia of chronic disease 1.
Overall, a comprehensive evaluation of iron status and inflammation is necessary to determine if high ferritin is an acute phase reactant or indicates true iron overload.
From the Research
Determining Acute Phase Reactant in High Ferritin Levels
To determine when high ferritin is an acute phase reactant, several factors and markers should be considered:
- Ferritin levels above 10,000 μg/L can indicate severe underlying conditions, including infections, cardiovascular issues, endocrinological, autoimmune, and malignancies 2
- In patients with inflammatory conditions, serum ferritin levels may not accurately reflect iron status due to its role as an acute-phase reactant 3, 4
- Transferrin saturation (TSAT) can be used as a marker of iron availability, and a threshold of <20% can be considered diagnostic for iron deficiency in certain conditions 4
- A serum ferritin threshold of <100 μg/L or TSAT < 20% can be considered diagnostic for iron deficiency in chronic heart failure, chronic kidney disease, and inflammatory bowel disease 4
- Elevated serum ferritin and IL-6 levels have been associated with increased mortality, and optimal ferritin levels for cardiovascular mortality reduction may range from 20 to 100 ng mL-1 5
Using Other Markers to Assess Inflammation
Other markers, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), can be used to assess inflammation and complement ferritin levels:
- ESR and CRP are markers of inflammatory conditions and can be used to monitor chronic and acute inflammatory conditions, respectively 6
- Fibrinogen, for which ESR is an indirect measure, has a longer half-life than CRP, making ESR helpful in monitoring chronic inflammatory conditions 6
- Many factors can result in falsely high or low ESR and CRP levels, and it is essential to consider these when interpreting results 6