How to manage anemia in a patient with low hemoglobin, elevated ferritin, and normal iron levels?

Management of Anemia with Elevated Ferritin in a 46-Year-Old Female

This patient has anemia of chronic disease (or functional iron deficiency) with markedly elevated ferritin (1090 ng/mL), and should NOT receive routine iron supplementation; instead, investigate the underlying cause of inflammation and consider erythropoiesis-stimulating agents (ESAs) only if she has chronic kidney disease or is receiving chemotherapy. 1

Understanding the Laboratory Pattern

This patient presents with:

• Anemia: Hemoglobin 10.2 g/dL (normal: 12-16 g/dL for women) 1
• Extremely elevated ferritin: 1090 ng/mL (normal: 15-150 ng/mL) 1
• Normal serum iron: 90 μg/dL 1
• Normal TIBC: 251 μg/dL 1
• Low transferrin: 187 mg/dL (suggests inflammation) 1

This pattern indicates anemia of chronic disease/inflammation, NOT iron deficiency anemia. 1 The extremely elevated ferritin (>500 ng/mL) with anemia suggests either:

1. Active inflammatory process with iron sequestration 1
2. Chronic disease state 1
3. Possible iron overload 1

Critical First Step: Do NOT Give Iron Supplementation

Avoid iron supplementation in patients with ferritin >500 ng/mL unless there is documented functional iron deficiency in the setting of ESA therapy. 1 This patient's ferritin of 1090 ng/mL is more than double this threshold. 1

• Iron therapy in patients with elevated ferritin levels carries risks of infection, cardiovascular events, and potential organ damage from iron overload 1, 2
• The safety of administering iron to patients with ferritin >500 ng/mL is unknown and potentially harmful 1, 2

Immediate Diagnostic Workup Required

Investigate the underlying cause of the elevated ferritin and anemia: 1

Look for inflammatory/chronic disease states:

• Chronic kidney disease: Check creatinine, eGFR, urinalysis 1, 3, 4
• Malignancy: Age-appropriate cancer screening, review for constitutional symptoms 1, 3
• Autoimmune disease: ANA, rheumatoid factor, inflammatory markers (CRP, ESR) 1
• Chronic infection: HIV, hepatitis C, tuberculosis screening if risk factors present 1
• Liver disease: Hepatic function panel (ferritin can be markedly elevated in hepatocellular injury) 1

Exclude other causes of anemia:

• Vitamin B12 and folate levels 3, 4
• Thyroid function tests 3, 4
• Reticulocyte count (to assess bone marrow response) 3, 4

Management Algorithm Based on Underlying Condition

If Chronic Kidney Disease is Present:

Consider ESA therapy only if: 3, 4

• Hemoglobin <10 g/dL (this patient qualifies at 10.2 g/dL, borderline) 3, 4
• Other causes of anemia excluded 3, 4
• Patient is symptomatic or at risk for transfusion 3, 4

Before initiating ESA therapy, ensure adequate iron availability: 1, 3, 4

• Calculate transferrin saturation (TSAT) = (serum iron ÷ TIBC) × 100 1
• For this patient: TSAT = (90 ÷ 251) × 100 = 36% 1
• This TSAT of 36% is adequate (>20%) despite the elevated ferritin 1

ESA dosing if CKD confirmed: 3, 4

• Epoetin alfa: 50-100 units/kg three times weekly IV/SC 4
• Darbepoetin alfa: 0.45 mcg/kg weekly or 0.75 mcg/kg every 2 weeks 3
• Target hemoglobin: Do NOT exceed 11 g/dL (increased risk of death, stroke, cardiovascular events) 3, 4
• Use the lowest dose to avoid transfusions 3, 4

If Active Malignancy with Chemotherapy:

ESA therapy may be considered only if: 3, 4

• Anemia is due to myelosuppressive chemotherapy 3, 4
• At least 2 more months of chemotherapy planned 3, 4
• Anticipated outcome is NOT cure 3, 4
• Hemoglobin <10 g/dL 3, 4

If Inflammatory Condition Identified:

Treat the underlying inflammatory disease first. 1 The anemia will often improve as inflammation resolves. 1

Monitor ferritin and hemoglobin levels: 1

• Recheck in 4-8 weeks after treating underlying condition 1
• If ferritin remains >800 ng/mL with persistent anemia, consider hematology referral 1

Special Consideration: Functional Iron Deficiency

The ONLY scenario where iron might be considered with ferritin >500 ng/mL: 1

If this patient has CKD and is started on ESA therapy, she may develop functional iron deficiency (iron stores present but unavailable for erythropoiesis). 1 This is diagnosed by: 1

• TSAT <25% despite ferritin 500-1200 ng/mL 1
• Inadequate response to ESA therapy 1

In this specific scenario only, consider a trial of IV iron: 1

• Ferric gluconate 125 mg IV over 8 consecutive hemodialysis sessions (if on dialysis) 1
• Monitor for hemoglobin response 1
• If no response after 8-10 doses, stop iron (indicates inflammatory block, not functional deficiency) 1

Monitoring Strategy

Weekly hemoglobin monitoring initially: 3, 4

• Check hemoglobin weekly until stable 3, 4
• Then monthly once stable 3, 4

Avoid rapid hemoglobin increases: 3, 4

• If hemoglobin rises >1 g/dL in 2 weeks, reduce or hold ESA therapy 3, 4
• Rapid rises increase cardiovascular risk 3, 4

Critical Pitfalls to Avoid

1. Do not give oral or IV iron based solely on low hemoglobin when ferritin is >500 ng/mL 1, 2
2. Do not target hemoglobin >11 g/dL with ESA therapy (increased mortality risk) 3, 4
3. Do not start ESA therapy without first investigating the cause of anemia 3, 4
4. Do not ignore the elevated ferritin - it signals inflammation or iron overload requiring investigation 1, 2
5. Patients with high ferritin levels (>800 ng/mL) and high-amplitude ferritin fluctuations have significantly higher risk of death and adverse events 2