What is the target ferritin level after iron repletion?

Target Ferritin Level After Iron Repletion

The target ferritin level after iron repletion is 50 ng/mL in the absence of inflammation, regardless of sex. 1

Primary Target and Rationale

• Aim for ferritin ≥50 ng/mL as this represents the body's physiologic threshold for adequate iron stores. 2
• Below 50 ng/mL, functional iron deficiency and symptoms commonly occur, even when patients are not overtly anemic. 2
• The 2024 American Journal of Hematology expert consensus guidelines explicitly state that in the absence of inflammation, the goal ferritin is 50 ng/mL, regardless of sex at birth. 1

Timing of Assessment

• Check ferritin and transferrin saturation (TSAT) 4 to 8 weeks after the last iron infusion—not sooner. 1
• Do not evaluate iron parameters within 4 weeks of total dose iron infusion, as circulating iron interferes with assays and produces spurious results. 1
• Hemoglobin should increase by 1-2 g/dL within 4-8 weeks of therapy. 1

Monitoring Strategy

• Obtain a complete blood count (CBC) along with ferritin and TSAT (calculated by dividing serum iron by total iron binding capacity). 1
• TSAT <20% has high sensitivity for diagnosing absolute or functional iron deficiency, while ferritin <100 ng/mL has low sensitivity (35-48%) for detecting deficiency. 1
• When ferritin and TSAT present discordant results (elevated ferritin with low TSAT), the TSAT is more reliable for identifying ongoing iron deficiency. 1

Special Considerations in Inflammatory States

• Ferritin is an acute-phase reactant that can be falsely elevated by chronic infection, inflammation, or tissue damage, masking depleted iron stores. 2
• In inflammatory conditions where ferritin is unreliable, soluble transferrin receptor (sTfR) is more sensitive as it is elevated in iron deficiency but not affected by inflammation. 1
• Reticulocyte hemoglobin content (CHr) or reticulocyte hemoglobin equivalent (RET-He) provide direct assessment of functional iron availability to erythropoietic tissue and are not affected by inflammation. 1

Context-Specific Targets

Heart Failure Patients

• While ferritin <100 ng/mL is commonly used as a diagnostic criterion in heart failure trials, TSAT and serum iron levels (rather than ferritin) correlate more strongly with functional capacity, hemoglobin levels, and prognosis. 3
• In the HEART-FID trial, changes in TSAT and iron levels over time related to changes in hemoglobin and 6-minute walk distance more than ferritin changes did. 3

Dialysis Patients

• Avoid excessive iron repletion in hemodialysis patients—the PIVOTAL trial is comparing conservative targets (ferritin >200 ng/mL, TSAT >20%) versus liberal targets (ferritin up to 700 ng/mL, TSAT up to 40%) to assess cardiovascular outcomes. 1
• Historical data suggest maintaining ferritin between 65-160 ng/mL in dialysis patients to avoid both iron depletion and overload. 4

Common Pitfalls

• Do not assume ferritin >50 ng/mL automatically indicates adequate iron stores—up to 40% of iron-deficient patients have ferritin levels between 15-50 ng/mL. 2
• Ferritin >50 ng/mL but <100 ng/mL should raise suspicion for iron deficiency, particularly with concurrent inflammation; additional testing with TSAT, C-reactive protein, or sTfR may be needed. 2
• Patients with normocytic anemia and ferritin >50 ng/mL should not automatically be considered iron-replete. 5

Ongoing Monitoring Frequency

• The frequency of post-repletion monitoring depends on the underlying cause of iron deficiency. 1
• Patients with ongoing blood loss (heavy menstrual bleeding, angiodysplasia, inflammatory bowel disease) or malabsorption (bariatric surgery, autoimmune gastritis, celiac disease) require more frequent laboratory monitoring and repeated iron administration. 1
• If the cause of iron deficiency has been eliminated, a single total dose iron infusion should suffice. 1