What is the appropriate workup and management for a patient with elevated ferritin (iron storage protein) levels?

Workup and Management of Elevated Ferritin

The appropriate workup for elevated ferritin should begin with complete iron studies, including serum iron, TIBC, transferrin saturation, and assessment for secondary causes, followed by targeted management based on the underlying etiology. 1

Initial Evaluation

Step 1: Complete Iron Studies

• Serum ferritin
• Serum iron
• Total iron binding capacity (TIBC)
• Transferrin saturation (TSAT)
• Reticulocyte hemoglobin content (CHr) and soluble transferrin receptor (sTfR) if available

Step 2: Additional Laboratory Testing

• Complete blood count with platelets
• Liver function tests (ALT, AST, bilirubin)
• Renal function (serum creatinine, eGFR)
• C-reactive protein (CRP) or other inflammatory markers
• Fasting glucose and lipid panel
• Vitamin D level

Step 3: Assess for Secondary Causes

• Inflammatory conditions
• Liver disease
• Malignancy
• Metabolic syndrome/obesity/diabetes
• Alcohol consumption
• Chronic infections
• Transfusion history

Interpretation of Ferritin Levels

Ferritin Level	Interpretation
<10 μg/L	Severe iron deficiency
<30 μg/L	Iron deficiency without inflammation
30-100 μg/L	Possible iron deficiency or anemia of chronic disease
50-100 μg/L	Target maintenance range for most patients
>100 μg/L	Possible anemia of chronic disease or iron overload
>1000 μg/L	High risk of cirrhosis (20-45%) [1]

Management Algorithm Based on Ferritin and Transferrin Saturation

1. Elevated Ferritin with High Transferrin Saturation (>45% women, >50% men)

• Consider iron overload disorders:

  • Hereditary hemochromatosis (consider HFE gene testing)
  • Transfusional iron overload
  • Other hereditary iron loading disorders

• Management:

  • Primary treatment: Therapeutic phlebotomy (400-500 mL weekly, containing 200-250 mg iron)
  • Target ferritin level: 50-100 μg/L 1
  • Monitor ferritin monthly during treatment

2. Elevated Ferritin with Normal/Low Transferrin Saturation

• Consider secondary causes:

  • Inflammatory conditions (including adult-onset Still's disease)
  • Liver disease (alcoholic, viral, NAFLD)
  • Malignancy (most common cause of markedly elevated ferritin) 2
  • Metabolic syndrome
  • Chronic kidney disease

• Management:

  • Treat underlying condition
  • Lifestyle modifications (weight loss, exercise, dietary changes)
  • Limit alcohol intake
  • Avoid iron supplements

3. Ferritin >1000 μg/L

• Requires urgent evaluation 1, 3
• Consider specialist referral (hematology, gastroenterology)
• Evaluate for organ damage (cardiac, hepatic, endocrine)
• Consider liver biopsy or MRI for quantification of liver iron

Special Considerations for Chelation Therapy

Chelation therapy should be initiated when:

• Ferritin levels >1000 ng/mL
• Transfusion-dependent patients requiring ≥2 units/month for >1 year
• Phlebotomy is contraindicated
• Patients with myelodysplastic syndromes with low-risk disease 1

Medication options include:

• Deferasirox: 14 mg/kg/day (for eGFR >60 mL/min/1.73m²) 4
• Deferoxamine: 20-60 mg/kg/day subcutaneous
• Deferiprone

Monitoring during chelation:

• Monthly ferritin levels
• Renal function
• Liver function
• Auditory and visual function 1, 4

Follow-up and Monitoring

• Iron overload patients: Monitor every 3 months during initial treatment, then annually after stabilization
• Non-iron overload patients: Regular monitoring of iron studies with annual follow-up if parameters remain normal
• Target maintenance ferritin: 50-100 μg/L 1

When to Refer to a Specialist

• Ferritin >1000 μg/L
• Unclear cause after initial evaluation
• Suspected hereditary hemochromatosis
• Evidence of organ damage
• Need for chelation therapy 1, 3

Common Pitfalls

1. Misinterpreting isolated ferritin elevation: 90% of elevated ferritin cases are due to non-iron overload conditions 3

2. Missing iron overload in patients with upper reference interval transferrin saturation: Iron overload can occur with ferritin elevation even when transferrin saturation is in the upper normal range 5

3. Overlooking malignancy: Malignancy is the most common cause of markedly elevated ferritin (>1000 μg/L) 2

4. Inappropriate chelation: Using chelation therapy when phlebotomy would be more appropriate or continuing chelation when iron burden approaches normal range 4

5. Inadequate monitoring: Failure to monitor for medication side effects during chelation therapy 1, 4