How are high iron levels managed?

Management of High Iron Levels

Therapeutic phlebotomy is the gold standard treatment for iron overload, with weekly blood removal of 400-500 mL until ferritin reaches 50-100 μg/L, followed by maintenance phlebotomy 3-4 times yearly for men and 1-2 times yearly for women. 1

Understanding Why Iron Levels Are High

High iron levels typically result from:

• Hereditary hemochromatosis (HH): Genetic disorder causing excessive iron absorption, most commonly from C282Y gene mutations 1
• Secondary iron overload: From repeated blood transfusions in conditions like thalassemia, chronic hemolytic anemia, or dyserythropoietic syndromes 1
• Chronic liver disease: Including hepatitis C, non-alcoholic fatty liver disease (NAFLD), or alcoholic liver disease 1

Initial Treatment Approach: Phlebotomy

Induction Phase

• Remove 400-500 mL of blood (containing 200-250 mg of iron) weekly or twice weekly as tolerated 1
• Target ferritin level: below 50-100 μg/L 1, 2
• Monitor hemoglobin, ferritin, and hematocrit before each session 1
• Check serum ferritin every 10-12 phlebotomies initially, then more frequently as levels approach target 2
• Postpone phlebotomy if anemia develops (hemoglobin drops significantly) 2

Maintenance Phase

• After reaching target ferritin, continue maintenance phlebotomy 3-4 times yearly for men and 1-2 times yearly for women 1
• Maintain ferritin between 50-100 μg/L 1, 2
• Monitor ferritin every 3-6 months during maintenance 2

Critical pitfall: Patients with ferritin >1000 μg/L or evidence of end-organ damage (elevated liver enzymes, cardiac dysfunction) require immediate aggressive phlebotomy and should be evaluated for cirrhosis 1

Alternative Treatment: Iron Chelation Therapy

Chelation is reserved for patients who cannot tolerate phlebotomy due to:

• Significant anemia 1
• Hemodynamic instability 1
• Malignancy 1
• Transfusion-dependent conditions with secondary iron overload 1

Available Chelating Agents

Deferoxamine (parenteral):

• Dose: 40 mg/kg/day subcutaneously over 8-12 hours nightly, 5-7 nights weekly 1, 3
• Maximum dose: 60 mg/kg/day 3
• Administered via portable infusion pump 1, 3
• Well-documented efficacy in preventing cardiac complications in thalassemia 1

Deferasirox (oral):

• FDA-approved for secondary iron overload from ineffective erythropoiesis 1
• Use in hereditary hemochromatosis remains investigational with safety concerns 1

Deferiprone:

• Alternative oral chelator mentioned but less commonly used 1

Important consideration: For patients with cardiac iron overload (T2* <10 ms on cardiac MRI), aggressive chelation therapy combined with standard heart failure medications (ACE inhibitors, diuretics, β-blockers) is essential 1

Dietary and Lifestyle Modifications

What to Avoid

• Iron supplements and multivitamins containing iron 1, 2
• Vitamin C supplements >500 mg/day (increases iron absorption) 1, 2
• Alcohol (increases iron absorption and worsens liver damage) 1, 2
• Raw shellfish (risk of Vibrio vulnificus infection in cirrhotic patients with iron overload) 2, 4

Dietary Approach

Dietary iron restriction is NOT a substitute for iron depletion therapy 1. Only 0.5-1.0 mg of excess iron is absorbed daily in hemochromatosis, which is minimal compared to the 200-250 mg removed per phlebotomy session 1. However, patients may:

• Minimize consumption of iron-rich foods like red meat 1
• Avoid iron-fortified foods 2, 4
• Maintain a broadly healthy diet without strict iron restriction 2

Critical caveat: Patients must understand that dietary modifications alone cannot adequately reduce iron stores—phlebotomy or chelation remains essential 1

Monitoring and Surveillance

During Active Treatment

• Hemoglobin and hematocrit before each phlebotomy 1, 2
• Serum ferritin every 10-12 phlebotomies, then more frequently near target 2
• Liver function tests regularly 4

Long-term Surveillance

• Ferritin monitoring every 3-6 months during maintenance 2
• Hepatocellular carcinoma screening in patients with cirrhosis (regardless of iron status normalization) 1, 2

Special Populations

Patients with Cardiac Iron Overload

Risk stratification by cardiac MRI T2* values 1:

• T2 >20 ms (green zone)*: Low risk, preventive chelation may delay cardiac complications
• T2 10-20 ms (yellow zone)*: Intermediate risk, monitor closely
• T2 <10 ms (red zone)*: High risk—requires immediate aggressive chelation plus standard heart failure therapy 1

Patients with Cirrhosis

• Continue phlebotomy to same ferritin targets (50-100 μg/L) 4
• Avoid raw shellfish due to infection risk 2, 4
• Consider liver transplantation if decompensated despite iron removal 1

Secondary Iron Overload

• Iron chelation (deferoxamine or deferasirox) is first-line for transfusion-dependent patients 1
• Phlebotomy may benefit porphyria cutanea tarda and NAFLD with iron overload 1
• Phlebotomy NOT recommended for mild secondary iron overload in hepatitis C or alcoholic liver disease 1

Prognosis

Early treatment before development of cirrhosis and diabetes restores survival to normal population levels 2. Improvements in cardiac function and resolution of refractory arrhythmias occur with aggressive iron removal, especially when initiated early 1.