How to manage low iron with elevated ferritin?

Management of Low Iron with Elevated Ferritin (22 μg/L with Ferritin 2505 ng/mL)

When encountering a patient with low iron (22 μg/L) but markedly elevated ferritin (2505 ng/mL), a thorough evaluation for underlying causes of iron overload or inflammatory conditions is essential before considering iron supplementation.

Initial Assessment

• The combination of low iron with markedly elevated ferritin (>1000 ng/mL) suggests an inflammatory condition, chronic disease, or potential iron overload disorder rather than true iron deficiency 1
• Serum ferritin is an acute-phase protein that increases during inflammation and infection, making it an unreliable marker of iron stores in inflammatory states 2
• Transferrin saturation should be measured to better assess iron status, as it helps distinguish between true iron deficiency, anemia of chronic disease, and iron overload conditions 1

Diagnostic Workup

• Measure transferrin saturation - this is crucial for determining whether the patient has true iron deficiency despite high ferritin 1
• If transferrin saturation is >45%, consider genetic testing for hemochromatosis (HFE gene mutations C282Y and H63D) 1, 3
• If transferrin saturation is low (<20%) despite high ferritin, consider anemia of chronic disease or inflammation 4
• Evaluate for secondary causes of hyperferritinemia including:
  • Chronic liver disease 3
  • Malignancy 3
  • Chronic kidney disease, especially in dialysis patients 5
  • Rheumatic conditions (adult-onset Still's disease, hemophagocytic lymphohistiocytosis) 3
  • Infections 3

Treatment Approach Based on Diagnosis

If Iron Overload is Confirmed (High Transferrin Saturation):

• Therapeutic phlebotomy is the cornerstone of treatment for confirmed hemochromatosis 1
• Target ferritin level should be <500 μg/L to avoid toxicity of iron overload 1
• Avoid iron supplementation as it could worsen iron overload 1

If Anemia of Chronic Disease is Suspected (Low Transferrin Saturation):

• Treat the underlying inflammatory condition 6
• Consider intravenous iron supplementation if there is evidence of functional iron deficiency 4
• The DRIVE study demonstrated that IV iron can be beneficial in patients with elevated ferritin (500-1200 ng/mL) and low transferrin saturation (<25%), improving hemoglobin levels more effectively than no iron supplementation 4
• Monitor for adverse events, as safety data for IV iron in patients with very high ferritin levels is limited 4

For Patients on Dialysis:

• If the patient is on hemodialysis, IV iron may be considered despite elevated ferritin if transferrin saturation is low 4
• In dialysis patients, serum ferritin levels between 65-160 ng/mL are suggested to avoid both iron depletion and overload 5
• Withhold iron therapy when ferritin exceeds 1000 ng/mL or transferrin saturation exceeds 50% 4

Monitoring and Follow-up

• Regular monitoring of iron parameters (ferritin, transferrin saturation) is essential during treatment 1
• For patients receiving IV iron despite high ferritin, closely monitor for adverse events including infusion reactions 4
• Consider the risk-benefit ratio of iron therapy, balancing the probability of improving anemia against potential risks of iron administration 4
• Reassess the underlying cause of elevated ferritin and adjust treatment accordingly 3

Important Caveats

• Ferritin levels >2500 ng/mL are significantly higher than those typically seen in dialysis patients and warrant thorough investigation 4
• The safety of administering IV iron to patients with ferritin levels >500 ng/mL remains uncertain, with limited long-term safety data 4
• Organ damage in hemochromatosis typically occurs at much higher ferritin levels than those observed in the general dialysis population 4
• Balance the need for iron supplementation against safety concerns, particularly in patients with extremely elevated ferritin levels 2