What is the management plan for a patient with hyperferritinemia and low TIBC?

Management of Hyperferritinemia with Low TIBC

The combination of elevated ferritin (800 µg/L) and low TIBC (176 mg/dL) suggests iron overload rather than iron deficiency, and requires immediate investigation to determine the underlying cause before initiating treatment. 1

Initial Diagnostic Workup

This iron profile pattern is concerning and demands systematic evaluation:

• Calculate transferrin saturation (TSAT) using the formula: (serum iron/TIBC) × 100 to assess iron loading status 1
• Obtain genetic testing for HFE mutations (C282Y and H63D) to evaluate for hereditary hemochromatosis, as this ferritin level warrants investigation 1
• Assess liver function with ALT, AST, and bilirubin to evaluate for hepatic involvement 1
• Check complete blood count to exclude hematologic disorders and assess for cytopenias 2
• Evaluate for secondary causes including chronic liver disease, metabolic syndrome, inflammatory conditions, and transfusion history 3

Clinical Context Determines Management

If Hereditary Hemochromatosis is Confirmed:

Initiate therapeutic phlebotomy immediately for patients with ferritin ≥800 µg/L, even in the absence of symptoms, as treatment is safe, inexpensive, and prevents progression to irreversible organ damage. 1

Phlebotomy Protocol:

• Remove 500 mL blood (one unit) weekly or twice weekly as tolerated 1
• Check hemoglobin/hematocrit before each phlebotomy and avoid reducing it by more than 20% from baseline 1
• Monitor ferritin every 10-12 phlebotomies (approximately every 3 months) during initial treatment 1
• Target ferritin level: 50-100 µg/L for both induction and maintenance therapy 1
• Once target achieved, assess need for maintenance phlebotomy (frequency varies from monthly to 1-2 units yearly) 1

Critical Safety Measures:

• Avoid vitamin C supplements as they accelerate iron mobilization and can cause toxic effects, particularly in patients with cardiac involvement 1
• No dietary iron restriction is necessary (only removes 2-4 mg/day) 1
• Avoid raw shellfish due to Vibrio vulnificus risk 1

If Secondary Iron Overload (Non-HFE):

For patients with transfusional iron overload or other secondary causes:

• Phlebotomy remains first-line if the patient can tolerate it and has adequate hemoglobin 1, 4
• Iron chelation therapy (deferasirox or deferoxamine) is indicated when phlebotomy is contraindicated or in dyserythropoietic conditions 1
  • Deferasirox dosing: 14 mg/kg/day orally for transfusional iron overload with ferritin >1000 µg/L 2
  • Monitor for renal toxicity, hepatotoxicity, and cytopenias monthly 2

If Dysmetabolic Hyperferritinemia (Normal/Low TSAT):

When TSAT is normal or low despite elevated ferritin, this suggests inflammation or metabolic syndrome rather than true iron overload 3:

• Do NOT initiate phlebotomy without confirming true iron overload 3
• Address underlying metabolic conditions (obesity, diabetes, fatty liver disease) 3
• Consider liver biopsy for hepatic iron concentration if diagnosis remains unclear and ferritin >1000 µg/L 1

Common Pitfalls to Avoid

• Never assume elevated ferritin alone equals iron overload - ferritin is an acute phase reactant and can be elevated in inflammation, infection, malignancy, and metabolic syndrome 1, 3
• Do not start phlebotomy in CKD patients receiving erythropoiesis-stimulating agents without careful consideration, as ferritin targets differ (200-500 µg/L acceptable) 1
• Avoid overchelation - continuing aggressive iron removal when ferritin falls below 500 µg/L can cause life-threatening complications 2
• Do not delay treatment in confirmed hemochromatosis - even asymptomatic patients with ferritin 800 µg/L benefit from prophylactic phlebotomy to prevent cirrhosis, diabetes, and cardiomyopathy 1

Monitoring During Treatment

• Monthly ferritin levels to guide therapy adjustments 1, 2
• Liver function tests monthly during active treatment 1, 2
• Screen for hepatocellular carcinoma if cirrhosis is present, even after successful iron depletion 1
• Baseline and annual auditory/ophthalmologic exams if using chelation therapy 2