How to manage a patient with low iron, high ferritin, and low iron saturation?

Management of Low Iron, High Ferritin, and Low Iron Saturation

This pattern indicates functional iron deficiency in the setting of inflammation, and iron supplementation should NOT be given when ferritin is elevated (288 ng/mL), as it is potentially harmful and not recommended. 1

Understanding the Laboratory Pattern

Your patient's iron studies reveal a paradoxical pattern that is characteristic of inflammation-induced iron sequestration:

• Low serum iron (14) and low transferrin saturation (7%) indicate insufficient iron available for erythropoiesis 1
• Elevated ferritin (288 ng/mL) suggests either adequate iron stores OR inflammation causing ferritin to rise as an acute phase reactant 1
• Low transferrin (129) and low TIBC (190) confirm inflammation is present, as these markers decrease during inflammatory states 1

This constellation is NOT true iron deficiency—it represents an inflammatory iron block where iron is sequestered in storage sites and unavailable for red blood cell production. 1

Critical Diagnostic Step: Assess for Inflammation

The most important next step is identifying the underlying inflammatory or chronic disease process:

• Check inflammatory markers: C-reactive protein (CRP), complete blood count with differential, liver transaminases 1
• Evaluate for chronic conditions: chronic kidney disease, heart failure, autoimmune disorders, malignancy, chronic infections 1, 2
• Consider hepcidin measurement if available, as elevated hepcidin in relation to transferrin saturation (hepcidin:TSAT ratio > upper reference limit) confirms functional iron deficiency from inflammation 1

Management Algorithm

Step 1: Do NOT Give Iron Supplementation Initially

Iron supplementation in the presence of normal or high ferritin values (>100 ng/mL) is not recommended and is potentially harmful. 1 Your patient's ferritin of 288 ng/mL falls well above this threshold.

• Oral iron will be poorly absorbed due to elevated hepcidin from inflammation 1
• IV iron carries risks of allergic reactions, hypophosphatemia, and iron overload without addressing the root cause 1, 2

Step 2: Treat the Underlying Inflammatory Condition

The primary intervention is identifying and treating the source of inflammation. 1 Once inflammation resolves:

• Ferritin levels will normalize and reflect true iron stores 1
• Hepcidin will decrease, allowing iron mobilization from stores 1
• Transferrin and TIBC will return to normal ranges 1

Step 3: Trial of IV Iron Only in Specific Circumstances

If inflammation persists despite treatment AND there is evidence of ongoing iron-restricted erythropoiesis (anemia with inadequate response to treatment of underlying disease):

• Consider a trial of IV iron: 50-125 mg weekly for 8-10 doses 1
• Monitor response: If hemoglobin does not increase after 8-10 doses, this confirms an inflammatory block rather than true iron deficiency, and further iron should be withheld 1
• Avoid chronic iron administration that maintains ferritin >500-800 ng/mL to prevent iron toxicity 1

Step 4: Reassess Iron Studies After Inflammation Resolves

• Recheck iron studies 8-10 weeks after treating the inflammatory condition (not earlier, as ferritin remains falsely elevated immediately after IV iron) 1
• If ferritin drops below 100 ng/mL with transferrin saturation <20% after inflammation resolves, this would indicate true iron deficiency requiring supplementation 1

Common Pitfalls to Avoid

Do not reflexively treat low serum iron and low transferrin saturation with iron supplementation without considering ferritin and inflammatory markers. 1 This is the most common error in managing these patients.

Do not interpret ferritin in isolation. 1, 3 Ferritin is an acute phase reactant that becomes misleadingly elevated during inflammation, masking true iron deficiency or falsely suggesting adequate stores.

Do not use oral iron in this setting. 1 Inflammation-induced hepcidin elevation blocks intestinal iron absorption, rendering oral supplementation ineffective.

Avoid vitamin C supplements, as they can mobilize iron to toxic levels in patients with elevated iron stores. 1

Special Considerations

In patients with chronic kidney disease specifically, functional iron deficiency is defined differently, with targets of transferrin saturation ≥20% and ferritin ≥100 ng/mL. 1 However, even in CKD, additional iron should not chronically maintain ferritin >800 ng/mL. 1

The goal of any iron therapy is to improve erythropoiesis, not to achieve specific laboratory targets. 1 In your patient's case, addressing inflammation is the pathway to improved erythropoiesis, not iron supplementation.