What is the management plan for a patient with iron overload?

Management of Iron Overload

This patient has significant iron overload (iron saturation 61%, serum iron 183 mg/dL) and requires immediate referral to a hematologist or hepatologist for evaluation of the underlying cause and initiation of treatment to prevent organ damage. 1

Immediate Diagnostic Workup

Your patient's iron studies indicate iron overload that requires urgent investigation:

• Iron saturation of 61% is markedly elevated (normal <45%) and suggests either hereditary hemochromatosis or secondary iron overload 1, 2
• Serum ferritin measurement is critical - you must obtain this immediately, as ferritin levels guide both diagnosis and treatment decisions 1
• HFE genetic testing should be performed to evaluate for hereditary hemochromatosis (specifically C282Y homozygosity, which is the most common cause) 1
• Liver MRI (T2)* should be obtained to quantify hepatic iron concentration and assess for organ damage 1
• Cardiac MRI (T2)* is indicated if there are any signs of heart disease or if ferritin is markedly elevated 1

Specialist Referral

Refer immediately to a hematologist or hepatologist who specializes in iron overload disorders 1. This is not a condition to manage in primary care alone given the complexity of diagnosis and risk of life-threatening organ damage.

Treatment Approach Based on Underlying Cause

If Hereditary Hemochromatosis (Most Likely)

Therapeutic phlebotomy is the first-line treatment and should be initiated once the diagnosis is confirmed 1, 3:

• Remove 1 unit (450-500 mL) of blood weekly until serum ferritin reaches 10-20 mcg/L 3
• Then maintain ferritin at ≤50 mcg/L with periodic phlebotomy 3
• This prevents cirrhosis, liver cancer, diabetes, cardiomyopathy, and hypogonadism when started before severe iron accumulation occurs 3

If Secondary Iron Overload (Transfusion-Dependent)

Iron chelation therapy is indicated if the patient has a history of chronic transfusions 1:

• Initiate chelation when ferritin reaches ≥1,000 ng/mL 1
• Options include deferasirox (oral), deferoxamine (parenteral), or deferiprone 1
• Deferasirox dosing: start at 14 mg/kg/day for transfusional iron overload 4
• Continue chelation as long as transfusions are needed and iron overload remains clinically relevant 1

Critical Monitoring Requirements

Monitor for organ damage that may already be present:

• Liver function tests and assessment for cirrhosis (ultrasound or FibroScan) 1
• Fasting glucose and HbA1c to screen for diabetes 3
• Echocardiogram if any cardiac symptoms or significantly elevated ferritin 1
• Testosterone/LH/FSH in men to assess for hypogonadism 3
• Joint examination for arthropathy, particularly metacarpophalangeal joints 3

Important Caveats

Do not delay referral - iron overload causes progressive, irreversible organ damage if untreated 5, 6. The heart and liver are particularly vulnerable, and cardiac siderosis can be fatal 5.

Investigate other causes if genetic testing is negative for C282Y homozygosity, including:

• Chronic liver disease (alcohol, viral hepatitis, fatty liver) 1
• Hematologic disorders with ineffective erythropoiesis 1
• Chronic transfusion history 1

Dietary counseling should include avoidance of medicinal iron supplements, excess vitamin C (which enhances iron absorption), and raw seafood (risk of Vibrio infection in iron-overloaded patients) 3.

Renal function monitoring is essential if chelation therapy is used, as deferasirox is contraindicated with eGFR <40 mL/min/1.73 m² 4.