Is treatment recommended for iron overload?

Treatment for Iron Overload IS Strongly Recommended

Treatment of iron overload is absolutely recommended and should be initiated in all patients with confirmed iron overload to prevent life-threatening complications including cardiac disease, hepatic cirrhosis, and endocrine dysfunction. 1, 2

When to Initiate Treatment

Therapeutic phlebotomy should be started when:

• Serum ferritin consistently exceeds 1,000 mcg/L in transfusion-dependent patients 1, 3
• Serum ferritin reaches 300 mcg/L or more in men with hereditary hemochromatosis 4
• Serum ferritin reaches 200 mcg/L or more in women with hereditary hemochromatosis 4
• Transferrin saturation exceeds 50% in males or 45% in females with evidence of iron overload 1
• Patient has received at least 100 mL/kg of packed red blood cells (approximately 20 units for a 40 kg person) 3

Primary Treatment Approach by Condition

Hereditary Hemochromatosis

Phlebotomy is the first-line treatment and must be initiated in all patients with evidence of iron overload 1, 2:

Induction Phase:

• Remove 450-500 mL of blood weekly or biweekly as tolerated 2, 5
• Monitor hemoglobin/hematocrit before each session 2
• Avoid reducing hemoglobin/hematocrit by more than 20% of baseline 5
• Continue until serum ferritin reaches 50-100 mcg/L 2, 4

Maintenance Phase:

• Continue periodic phlebotomy lifelong to maintain ferritin at 50 mcg/L or less 1, 2, 4
• Typical frequency: 3-4 times yearly for men, 1-2 times yearly for women 5

Transfusion-Dependent Conditions (MDS, Thalassemia, Sickle Cell Disease)

Iron chelation therapy is the treatment of choice when phlebotomy is not feasible 1:

• Initiate when ferritin reaches 1,000 ng/mL 1, 3
• Start when transfusion requirement is 2 units/month or more for greater than one year 1
• Continue as long as transfusion therapy continues and iron overload remains clinically relevant 1

Available chelators include:

• Deferasirox (oral) - most studied for non-hemochromatosis iron overload 1, 3
• Deferoxamine (parenteral) - traditional option 1, 6
• Deferiprone (oral) - alternative agent 6

Critical Monitoring Requirements

Before initiating treatment, evaluate 3:

• Serum ferritin level
• Baseline renal function with duplicate serum creatinine and eGFR calculation
• Serum transaminases and bilirubin
• Urinalysis and serum electrolytes for renal tubular function
• Baseline auditory and ophthalmic examinations

During treatment, monitor 1, 5:

• Serum ferritin at least every 3 months in transfusion-dependent patients
• Renal function at least monthly (weekly for first month if baseline impairment) 3
• Liver enzymes every 2 weeks during first month, then monthly 3
• Hemoglobin/hematocrit before each phlebotomy 2

Patients Who Benefit Most from Treatment

Highest priority for iron overload treatment 1:

• Transfusion-dependent patients requiring ≥2 units/month for >1 year
• Patients with ferritin >1,000 ng/mL
• Low-risk MDS patients (IPSS low or intermediate-1)
• Patients with life expectancy ≥1 year
• Candidates for allogeneic stem cell transplant
• Patients requiring organ function preservation

Critical Contraindications and Precautions

Deferasirox is contraindicated when 3:

• eGFR <40 mL/minute/1.73 m² in adults and pediatrics
• Severe (Child-Pugh C) hepatic impairment
• Advanced hematologic malignancies with low platelet counts (GI hemorrhage risk)

Phlebotomy should be interrupted for 5:

• Acute illnesses causing volume depletion (vomiting, diarrhea)
• Decreased oral intake
• Fever or acute illness affecting renal perfusion

Dietary and Lifestyle Modifications

Patients must avoid 2, 4:

• Iron supplements and iron-fortified foods
• Supplemental vitamin C (enhances iron absorption)
• Raw or undercooked shellfish (Vibrio vulnificus infection risk)
• Excessive alcohol consumption (increases iron absorption and liver damage)

Limit red meat consumption 2

Consequences of Untreated Iron Overload

Failure to treat iron overload results in 1:

• Cardiac complications including cardiomyopathy and arrhythmias
• Hepatic cirrhosis and hepatocellular carcinoma (30% of hemochromatosis-related deaths) 2
• Endocrine dysfunction (diabetes mellitus, hypogonadism)
• Increased morbidity and mortality

Early treatment before development of cirrhosis and diabetes significantly improves survival 2, 4

Special Populations

Patients with cirrhosis require 1, 2:

• Regular screening for hepatocellular carcinoma
• Continued phlebotomy or chelation despite cirrhosis presence
• More frequent monitoring

Pediatric patients (≥2 years) with transfusional iron overload 3:

• Higher risk of renal toxicity with chelation
• Require more frequent monitoring during volume depletion
• Should interrupt chelation during acute illnesses