What is the management of secondary hemochromatosis?

Management of Secondary Hemochromatosis

Treatment of secondary hemochromatosis must be tailored to the underlying cause: use phlebotomy for conditions with adequate bone marrow function (porphyria cutanea tarda, African iron overload, post-transplant states), but iron chelation therapy is mandatory for patients with ineffective erythropoiesis or chronic transfusion-dependent anemias where phlebotomy would worsen anemia. 1

Treatment Selection Based on Underlying Etiology

Phlebotomy-Appropriate Conditions

Phlebotomy is the treatment of choice for secondary iron overload when bone marrow function is preserved:

• Porphyria cutanea tarda (PCT): Phlebotomy clearly reduces skin manifestations and is first-line therapy, with total iron stores rarely exceeding 4-5 g 1
• African iron overload: Phlebotomy has demonstrated reduction in morbidity and mortality 1
• Post-transplant iron overload: Patients may undergo phlebotomy after bone marrow transplantation once erythropoiesis recovers 1

Phlebotomy shows limited or no benefit in:

• Alcoholic liver disease (ALD): No published evidence supports phlebotomy benefit 1
• Chronic hepatitis C with mild iron overload (HIC < 2500 μg/g dry weight): Phlebotomy reduces ALT levels and achieves marginal histologic improvement but has no effect on virologic clearance; currently not recommended for mild overload 1
• Non-alcoholic fatty liver disease (NAFLD): Studies show benefit with improvement in insulin resistance parameters and ALT reduction, though large-scale confirmatory studies are needed 1

Iron Chelation-Required Conditions

Iron chelation therapy with deferoxamine or deferasirox is the treatment of choice for secondary iron overload associated with ineffective erythropoiesis or chronic transfusion dependence: 1

• β-thalassemia major: Multiple studies document deferoxamine efficacy in preventing iron overload complications 1
• Myelodysplastic syndromes (MDS): Iron chelation is appropriate for lower-risk MDS patients requiring prolonged transfusion therapy 2
• Sideroblastic anemia and chronic hemolytic anemias: Chelation prevents organ damage from transfusional iron accumulation 1, 2

Iron Chelation Protocols

Deferoxamine (Parenteral)

Deferoxamine is administered by continuous subcutaneous infusion using a battery-operated pump: 1

• Dosing: 40 mg/kg/day for 8-12 hours nightly, 5-7 nights weekly 1
• Maximum urinary iron excretion: Achieved with approximately 2 g per 24 hours 1
• Target: Reduce hepatic iron concentration (HIC) to < 15,000 μg/g dry weight, which significantly reduces clinical disease risk 1
• Limitations: Cost, parenteral administration requirement, discomfort, inconvenience, and neurotoxicity 1

Deferasirox (Oral)

Deferasirox is an FDA-approved oral iron chelator for secondary iron overload due to ineffective erythropoiesis: 1

• Advantages: Oral administration improves compliance compared to parenteral deferoxamine 2
• Safety concerns: Risk of renal or hepatic failure; recent complications have tempered enthusiasm for use in hereditary hemochromatosis 1, 2
• Not indicated: Should not be used in patients with advanced liver disease 3
• FDA indication: Approved for transfusional iron overload in chronic anemia, but NOT for primary hemochromatosis 4

Monitoring Iron Reduction

Monitoring iron burden during chelation therapy is more challenging than in hereditary hemochromatosis:

• Serum ferritin is unreliable: Unlike hereditary hemochromatosis, ferritin levels can be misleading in secondary iron overload due to inflammation 1
• Hepatic iron concentration (HIC) is the gold standard: Provides accurate quantitative assessment of iron balance 1
• Repeat liver biopsy may be necessary: Required in some patients to assess therapy progress and ensure adequate chelation 1
• 24-hour urinary iron excretion: Can be helpful for monitoring 1
• MRI-based assessment: Recent magnetic resonance imaging programs show promise as noninvasive methods to evaluate HIC 1

Common Pitfalls and Caveats

Critical errors to avoid:

• Do not use phlebotomy in transfusion-dependent anemias: This worsens anemia and is contraindicated in conditions with ineffective erythropoiesis 1, 2
• Avoid vitamin C supplements: These enhance iron absorption and can worsen iron overload 1, 5, 3
• Do not rely solely on ferritin in inflammatory conditions: Ferritin is an acute phase reactant and may be falsely elevated 1, 5
• Recognize that phlebotomy is NOT indicated for primary hemochromatosis treatment via chelation: Phlebotomy remains first-line for hereditary hemochromatosis 4

Hepatocellular Carcinoma Surveillance

Patients with secondary iron overload and cirrhosis require regular HCC screening:

• Follow AASLD guidelines for HCC surveillance: This applies to all cirrhotic patients regardless of iron overload etiology 1
• Risk remains elevated: HCC accounts for approximately 30% of hemochromatosis-related deaths 3
• Screening continues even after iron depletion: Iron removal does not eliminate HCC risk in established cirrhosis 1