What is the initial treatment approach for a new onset hemochromatosis patient?

Initial Hematology Note for New Onset Hemochromatosis

Assessment and Diagnosis

This patient has newly diagnosed hemochromatosis requiring immediate initiation of therapeutic phlebotomy to prevent progressive organ damage and improve survival. 1, 2

Baseline Evaluation Required Before Treatment

Prior to initiating therapy, obtain the following studies 1, 3:

• Serum ferritin level to quantify iron burden and establish baseline 1, 3
• Liver function tests (ALT, AST, bilirubin) to assess hepatic involvement and establish baseline 1, 3
• Renal function assessment including serum creatinine in duplicate (due to measurement variations), calculate eGFR using appropriate prediction equations (CKD-EPI or MDRD for adults, Schwartz for pediatrics), urinalysis, and serum electrolytes to evaluate renal tubular function 1, 3
• Complete blood count to ensure adequate hemoglobin for phlebotomy (must be ≥12 g/dL) 1, 3
• Baseline auditory and ophthalmic examinations including slit lamp and dilated fundoscopy 1, 4
• Assessment for cirrhosis through imaging or clinical evaluation, as this determines HCC surveillance needs 5

Genetic Testing and Family Screening

• HFE genotype testing should be documented (C282Y homozygosity is most common) 1
• First-degree relatives (especially siblings) should be tested for HFE variants as they are at highest risk 1

Treatment Plan: Induction Phase

Therapeutic Phlebotomy Protocol

Initiate weekly therapeutic phlebotomy immediately as first-line treatment to achieve iron depletion. 1, 2, 5

• Remove 450-500 mL of blood weekly (or biweekly if patient cannot tolerate weekly schedule) 1, 2, 3
• Target serum ferritin of 50 μg/L during induction phase (not lower to avoid iron deficiency) 1, 2
• Check hemoglobin/hematocrit before each phlebotomy session - do not allow hemoglobin to fall by more than 20% from baseline 2, 3

Monitoring During Induction

• If hemoglobin <12 g/dL: reduce phlebotomy frequency 1, 2
• If hemoglobin <11 g/dL: discontinue phlebotomy temporarily and reassess 1, 2
• Monitor serum ferritin monthly (or after every 4th phlebotomy) 1, 3
• When ferritin decreases below 200 μg/L: check ferritin every 1-2 treatment sessions until target of 50 μg/L is reached 1, 2

Maintenance Phase (After Achieving Iron Depletion)

Continue lifelong phlebotomy at reduced frequency to maintain serum ferritin between 50-100 μg/L. 1, 2, 5

• Typical maintenance frequency: every 2-6 times per year (individualized based on iron reaccumulation rate) 2, 5
• Monitor serum ferritin and transferrin saturation every 6 months during maintenance 2, 3
• Adjust phlebotomy frequency to keep ferritin in target range of 50-100 μg/L 1, 2

Alternative Treatment Options

Erythrocytapheresis

• Consider as alternative to standard phlebotomy - removes up to 3 times more red blood cells per session, requiring 50-70% fewer procedures 2, 6
• May be more cost-effective during induction phase due to fewer interventions and reduced productivity loss 1, 6
• Preferred in selected cases where minimizing treatment visits is important 1

Iron Chelation Therapy (Second-Line Only)

Use only when phlebotomy is contraindicated or not tolerated. 1, 5

• Deferasirox (oral) is the most studied chelation option 1, 5
• Contraindicated in advanced liver disease - do not use in patients with severe hepatic impairment 1, 4
• Not FDA-approved for hemochromatosis and associated with significant side effects including GI symptoms, renal impairment, and hepatotoxicity 1, 4
• Deferoxamine 20-40 mg/kg/day subcutaneously is traditional chelation alternative 3

Dietary and Lifestyle Modifications

Critical Avoidances

Dietary modifications supplement but do not substitute for iron removal therapy. 1

• Avoid iron supplements and iron-fortified foods entirely 1, 5
• Avoid supplemental vitamin C, especially before iron depletion, as it accelerates iron mobilization and increases oxidative stress 1, 3
• Limit red meat consumption 1
• Restrict alcohol intake during iron depletion phase; patients with cirrhosis must abstain completely 1, 5
• Avoid raw or undercooked shellfish and wound exposure to seawater due to risk of fatal Vibrio vulnificus infection in iron-overloaded patients 1, 5

Moderate Consumption

• Fruit juices and citrus fruits should be consumed in moderation and not with meals 1

Special Monitoring Considerations

Hepatocellular Carcinoma Surveillance

• Patients with cirrhosis require lifelong HCC screening (accounts for ~30% of hemochromatosis-related deaths) 5
• Advanced fibrosis risk is modified by alcohol consumption, type 2 diabetes, and viral hepatitis 1

Critical Safety Monitoring

• Monitor for overchelation: if ferritin falls below 1000 μg/L at 2 consecutive visits, consider dose reduction (especially if phlebotomy frequency is high) 1, 4
• If ferritin falls below 500 μg/L: interrupt phlebotomy and continue monthly monitoring 1, 4
• Periodically check plasma folate and cobalamin in patients requiring numerous venesections; supplement if deficient 1

Expected Outcomes

Early diagnosis and treatment before development of cirrhosis and diabetes significantly improves survival. 5

• Symptoms often improved by phlebotomy: weakness, fatigue, elevated liver enzymes, right upper quadrant pain, and hyperpigmentation 7
• Complications prevented when treated early: hepatic cirrhosis, primary liver cancer, diabetes mellitus, hypogonadism, arthropathy, and cardiomyopathy 7
• Iron removal does not reverse established cirrhosis - patients with decompensated liver disease may require transplantation 2

Common Pitfalls to Avoid

• Do not delay treatment waiting for symptoms - initiate phlebotomy based on ferritin levels alone 2, 7
• Do not over-treat - avoid continuing aggressive phlebotomy when ferritin approaches normal range, as this can cause life-threatening complications 4
• Do not use aluminum-containing antacids with deferasirox if chelation therapy is needed 4
• Monitor elderly patients more frequently for toxicity as they have higher risk of serious adverse events 4