What are the indications for phlebotomy in patients with hemochromatosis?

Indications for Phlebotomy in Hemochromatosis

Phlebotomy is indicated in patients with hemochromatosis who have evidence of iron overload, defined as elevated transferrin saturation (>45% in females, >50% in males) and elevated ferritin (>200 μg/L in females, >300 μg/L in males and post-menopausal women). 1

Primary Indications for Phlebotomy

• Patients with confirmed hemochromatosis (HFE gene mutations, particularly C282Y homozygotes) with evidence of iron overload 1
• Patients with non-HFE iron overload who have elevated hepatic iron concentration 1
• Patients with end-organ damage due to iron overload 1
• Patients with elevated serum ferritin without significant liver disease (ALT, AST elevation) but with ferritin <1000 μg/L 1

Phlebotomy Protocol

Initial Iron Depletion Phase

• Weekly or biweekly phlebotomy (400-500 mL) until target ferritin level is reached 1
• Target ferritin level for induction phase: <50 μg/L 1
• Monitor hemoglobin before each phlebotomy session 1
• Reduce frequency if hemoglobin falls below 12 g/dL 1
• Discontinue phlebotomy if hemoglobin falls below 11 g/dL 1
• Check serum ferritin every 10-12 phlebotomies (or monthly) 1, 2
• When ferritin falls below 200 μg/L, check ferritin every 1-2 sessions 1

Maintenance Phase

• Transition to maintenance phase once ferritin reaches target level of 50 μg/L 1
• Maintenance phlebotomy every 1-4 months to maintain ferritin between 50-100 μg/L 1, 2
• Monitor serum ferritin every 6 months to adjust treatment schedule 1
• Individualize frequency based on iron reaccumulation rate (average rise in ferritin is approximately 100 μg/L per year without treatment) 1, 2

Special Considerations

Age-Related Adjustments

• In elderly patients, more relaxed ferritin targets may be appropriate during maintenance phase 1
• For women: <200 μg/L 1
• For men: <300 μg/L 1

Monitoring Parameters

• Transferrin saturation should be monitored, although evidence-based target levels are lacking 1
• Some evidence suggests that joint symptoms may be related to transferrin saturation >50% regardless of ferritin levels 1
• Monitor folate and vitamin B12 levels periodically, especially in patients requiring numerous phlebotomies 1
• Consider monitoring soluble transferrin receptor levels when ferritin is of limited value (e.g., in inflammatory conditions) 3

Complications and Cautions

• Avoid iron supplementation and iron-fortified foods 1
• Avoid vitamin C supplements, especially before iron depletion 1, 2
• Limit red meat consumption 1
• Restrict alcohol intake, especially during iron depletion phase 1
• Patients with cirrhosis should abstain from alcohol completely 1
• Be vigilant for excessive phlebotomy leading to iron deficiency, which can cause persistent symptoms 4

Phlebotomy in Secondary Iron Overload

• Phlebotomy is indicated in porphyria cutanea tarda 1
• May be beneficial in non-alcoholic fatty liver disease (NAFLD) with iron overload 1
• Not routinely recommended for mild secondary iron overload in chronic hepatitis C 1
• For secondary iron overload due to ineffective erythropoiesis, iron chelation therapy is preferred over phlebotomy 1

Compliance Considerations

• Patient compliance with maintenance therapy decreases by approximately 6.8% annually 5
• C282Y homozygotes show better compliance with maintenance therapy than patients with other genotypes 5
• Only about one-third of patients adhere strictly to weekly phlebotomy schedules 5

Phlebotomy remains the cornerstone of hemochromatosis treatment, with the primary goal of preventing complications such as cirrhosis, hepatocellular carcinoma, diabetes, and arthropathy through effective iron depletion and maintenance therapy.