Target Ferritin Levels in Patients with Inflammation
In patients with inflammation, target ferritin levels should be adjusted upward from the standard threshold, with iron deficiency diagnosed at ferritin <100 μg/L or transferrin saturation <20%, and treatment goals aiming for ferritin levels that account for the acute-phase reactant nature of ferritin rather than using standard cutoffs. 1, 2, 3
Understanding Ferritin as an Acute-Phase Reactant
Ferritin is an acute-phase reactant that rises during inflammation independent of actual iron stores, making traditional cutoffs unreliable in inflammatory states. 1, 2 In the presence of inflammation, serum ferritin up to 100 μg/L may still be consistent with iron deficiency, as proinflammatory cytokines trigger increased hepcidin expression, which restricts iron availability for erythropoiesis despite normal or elevated ferritin levels. 2, 3
Diagnostic Thresholds for Iron Deficiency with Inflammation
The standard threshold for iron deficiency (<30 μg/L) does not apply in inflammatory conditions. 3 Instead, use the following adjusted criteria:
Ferritin <100 μg/L is diagnostic for iron deficiency in patients with chronic heart failure, chronic kidney disease, and inflammatory bowel disease, regardless of inflammation status. 2, 3
If ferritin is 100-300 μg/L, transferrin saturation <20% is required to confirm iron deficiency. 3
Transferrin saturation <20% has high sensitivity for diagnosing absolute or functional iron deficiency even when ferritin is elevated due to inflammation. 1, 2
Target Ferritin Levels During Treatment
In the absence of inflammation, the goal ferritin is 50 ng/mL, regardless of sex. 1 However, in patients with inflammatory conditions, the target ferritin should be adjusted upward:
For patients with chronic kidney disease on erythropoiesis-stimulating agents (ESAs), administer supplemental iron when serum ferritin is <100 mcg/L or transferrin saturation is <20%. 4
The majority of patients with CKD will require supplemental iron during ESA therapy, and ferritin synthesis is blunted during inflammation even when absolute iron deficiency is present. 1, 4
Monitoring Iron Parameters in Inflammatory States
Evaluate transferrin saturation alongside ferritin—never use ferritin alone to assess iron status in inflammatory conditions. 1, 2 The pattern of laboratory values provides critical diagnostic information:
Ferritin >100 μg/L with transferrin saturation <16% suggests anemia of chronic disease. 2
Elevated ferritin with low transferrin saturation (<20%) indicates functional iron deficiency or inflammatory iron block. 1
Measure inflammatory markers (CRP, ESR) alongside ferritin to determine if inflammation is present and affecting interpretation. 2
Treatment Approach
The first step in managing inflammation-induced hyperferritinemia is treating the underlying inflammatory condition. 2 When iron deficiency is confirmed despite elevated ferritin:
Administer intravenous iron rather than oral iron, especially in cases of functional iron deficiency with inflammation. 2
IV iron formulations such as ferric derisomaltose, iron sucrose, or ferric carboxymaltose are recommended for patients with inflammatory bowel disease and other chronic inflammatory conditions. 1, 2
Post-Treatment Monitoring
Evaluate CBC and iron parameters 4-8 weeks after iron infusion—do not check iron parameters within 4 weeks of IV iron administration, as circulating iron interferes with assays and leads to spurious results. 1, 2
Expect hemoglobin to increase by 1-2 g/dL within 4-8 weeks of therapy. 1, 2 In patients with inflammation, the goal ferritin level should be adjusted upward compared to patients without inflammation. 2
Critical Pitfalls to Avoid
Do not rely solely on ferritin levels to assess iron status in inflammatory states—ferritin can be elevated while patients remain functionally iron deficient due to hepcidin-mediated iron sequestration. 2, 3
Do not withhold iron therapy based on elevated ferritin alone if transferrin saturation or other markers suggest iron deficiency. 2
Do not assume normal iron stores based on normal or elevated ferritin when inflammation is present—inflammation increases ferritin by approximately 30-90% depending on the phase of inflammatory response. 2, 5
Alternative Markers When Ferritin is Unreliable
When ferritin is unreliable due to inflammation:
Soluble transferrin receptor (sTfR) is elevated in iron deficiency and not affected by inflammation, though it has limitations including long turnaround time and elevation with increased erythropoietic activity. 1
Reticulocyte hemoglobin content (CHr) or equivalent (RET-He) provides direct assessment of functional iron availability and is immediately available on certain auto analyzers. 1