What is the best course of action for a 54-year-old patient with normocytic anemia, low iron levels, and significantly elevated ferritin levels?

Anemia of Chronic Disease/Inflammation with Functional Iron Deficiency

This patient has anemia of chronic disease (ACD) with functional iron deficiency, characterized by low serum iron, low transferrin saturation at the lower limit of normal (0.15), and elevated ferritin (599 µg/L), indicating iron sequestration rather than true iron deficiency. The normocytic indices (MCV 89 fL) and elevated platelet count further support an inflammatory process 1, 2.

Diagnostic Interpretation

The laboratory pattern is classic for anemia of inflammation:

• Low serum iron (12 µmol/L) with normal/elevated ferritin (599 µg/L) distinguishes this from true iron deficiency anemia, where ferritin would be low 1, 2
• Transferrin saturation at 0.15 (lower limit of normal) indicates functional iron restriction—iron is present in stores but not available for erythropoiesis 3, 1
• Normal transferrin (3.1 g/L) helps exclude hemochromatosis and confirms the laboratory comment's interpretation 3
• The elevated ferritin as an acute phase reactant reflects underlying inflammation, infection, or chronic disease 1, 2

Immediate Management Priorities

1. Identify the Underlying Cause

The primary focus must be identifying and treating the underlying inflammatory/chronic disease causing the anemia 1, 2. Key investigations should include:

• Comprehensive infection workup (urinalysis, chest imaging, inflammatory markers like CRP/ESR)
• Malignancy screening appropriate for age and risk factors (the patient is 54 years old) 2
• Autoimmune/rheumatologic evaluation if clinically indicated
• Assessment for chronic liver disease (fatty liver mentioned in lab comment) or excessive alcohol use 3

2. Iron Supplementation is NOT Indicated

Do not give iron supplementation in this patient 1, 2. The rationale:

• Ferritin of 599 µg/L indicates adequate iron stores 3
• The problem is iron sequestration (functional deficiency), not absolute deficiency 1
• Iron supplementation will not improve anemia and may cause iron overload, as the body cannot utilize the iron appropriately 3
• The transferrin saturation of 0.15, while at the lower limit, combined with elevated ferritin, confirms iron is trapped in reticuloendothelial stores 3, 1

3. Avoid Phlebotomy

Phlebotomy is contraindicated given the existing anemia (Hb 116 g/L) 3, 4. While the ferritin is elevated, this represents inflammatory sequestration rather than true iron overload requiring depletion 1.

Treatment Algorithm

Step 1: Address Underlying Disease

• Treat any identified infection, inflammation, or chronic disease as this is the only definitive way to resolve anemia of chronic disease 1, 2
• Monitor inflammatory markers (CRP, ESR) to assess disease activity

Step 2: Monitor Without Intervention (if mild/asymptomatic)

• If hemoglobin remains >100 g/L and patient is asymptomatic, observation is appropriate while treating underlying cause 3, 1
• Recheck CBC and iron studies in 1-3 months 3

Step 3: Consider Erythropoiesis-Stimulating Agents (ESAs) if Severe/Symptomatic

If hemoglobin falls below 100 g/L or patient develops significant anemia-related symptoms, ESA therapy may be considered 3:

• This decision requires weighing risks (thrombosis, cardiovascular events, potential malignancy concerns) against benefits 3
• ESAs can overcome cytokine-mediated suppression of erythropoiesis in ACD 2
• Contraindications include active malignancy (especially if curative treatment planned) or history of stroke 3

Step 4: Intravenous Iron—Controversial in This Context

The role of IV iron with ferritin >500 µg/L is limited and controversial 3:

• One study (DRIVE trial) showed benefit in hemodialysis patients with ferritin 500-1200 µg/L and transferrin saturation <25% when combined with ESAs 3
• However, safety data are limited, and this approach is not recommended outside of CKD/dialysis populations 3
• For this patient without CKD, IV iron is not indicated 3

Key Pitfalls to Avoid

1. Do not misinterpret this as iron deficiency anemia requiring iron supplementation—the elevated ferritin excludes this diagnosis 1, 5, 6
2. Do not initiate phlebotomy based on elevated ferritin alone—the patient is already anemic and the ferritin elevation is inflammatory, not from iron overload 3, 4
3. Do not ignore the underlying cause—failure to identify and treat the primary disease will result in persistent anemia 1, 2
4. Monitor ferritin levels if any iron is given—ferritin should not exceed 500 µg/L to avoid toxicity, though in this case iron is contraindicated anyway 3

Monitoring Plan

• Repeat CBC in 4-8 weeks after addressing underlying cause 3
• Repeat iron studies (iron, ferritin, transferrin saturation) in 3 months to assess response to treatment of underlying disease 3
• If ferritin continues rising or new symptoms develop, investigate for additional causes including malignancy, ongoing infection, or autoimmune disease 3, 1