Management of Anemia with Hyperferritinemia and Low Iron Saturation
This patient has anemia of chronic disease (functional iron deficiency) characterized by elevated ferritin (652 ng/mL), low iron saturation (9.8%), and low serum iron (15), requiring investigation of the underlying inflammatory or chronic condition before considering iron supplementation. 1
Diagnostic Interpretation
The laboratory pattern reveals:
- Elevated ferritin (652 ng/mL) with low transferrin saturation (9.8%) indicates functional iron deficiency, where iron is sequestered in storage sites but unavailable for erythropoiesis 1
- Normal MCV (82.3 fL) suggests this is not classic iron deficiency anemia, which typically presents with microcytosis 1
- Low TIBC (148) confirms anemia of chronic disease rather than true iron deficiency, where TIBC would be elevated 1
This constellation represents functional iron deficit, a clinical situation occurring when ferritin levels exceed 100 mg/mL despite the presence of functional iron deficiency 1. In these cases, ferritin acts as an acute phase reactant, generating misleading results 1.
Underlying Cause Investigation
Priority: Identify the inflammatory or chronic disease process driving this pattern 1
Key conditions to evaluate:
- Chronic inflammatory disorders (rheumatologic conditions, infections) 1, 2
- Chronic liver disease (hepatitis B/C, alcoholic liver disease, non-alcoholic fatty liver disease) 2, 3
- Malignancy 1, 2
- Chronic kidney disease 1
- Hemolytic anemia (check haptoglobin, reticulocyte count) 1, 2
Clinical assessment should focus on:
- Alcohol consumption history (can disrupt iron metabolism and elevate ferritin) 4, 3
- Signs of metabolic syndrome 5, 6
- Inflammatory markers (CRP, ESR) 1, 6
- Liver function tests 5, 6
Iron Supplementation Decision
When NOT to Give Iron
Iron supplementation is NOT recommended when ferritin is normal or elevated without documented iron deficiency, as it is potentially harmful 1. This patient's ferritin of 652 ng/mL exceeds safety thresholds.
When to Consider Iron Despite Elevated Ferritin
Iron therapy may be considered in highly selected circumstances when:
- Transferrin saturation remains <20% (present in this patient at 9.8%) 1
- Patient is receiving erythropoiesis-stimulating agents (ESAs) 1
- Underlying condition creates ongoing functional iron deficiency 1
The DRIVE study demonstrated that hemodialysis patients with ferritin 500-1200 ng/mL and transferrin saturation <25% showed hemoglobin improvement with IV iron 1. However, this was in the specific context of ESA therapy and chronic kidney disease.
Route and Monitoring if Iron is Given
If iron supplementation is deemed necessary after careful consideration:
- Intravenous iron is preferred over oral for functional iron deficiency, as oral iron absorption is impaired by elevated hepcidin 1
- Ferritin should be monitored and preferably not exceed 500 mg/L to avoid iron overload toxicity 1
- Single doses should not exceed maximum recommended amounts, with doses repeated every 3-7 days 1
- Combination with EPO may prevent toxic iron loading in some patients, though evidence is limited 1
Critical Pitfalls
Common mistake: Treating elevated ferritin as iron overload requiring phlebotomy 1. This patient does NOT have iron overload—the low transferrin saturation excludes hereditary hemochromatosis and other primary iron overload disorders 2, 5.
Second pitfall: Reflexively giving iron for anemia without addressing the underlying cause 1. The hemoglobin of 10.5 g/dL requires treatment of the primary inflammatory or chronic condition, not empiric iron 1.
Third pitfall: Misinterpreting ferritin in inflammatory states 1. Ferritin >100 mg/mL in the presence of low transferrin saturation represents functional deficit, not true iron stores 1.