What are the guidelines for performing phlebotomy in patients with iron overload disorders or polycythemia vera?

Guidelines for Performing Phlebotomy in Iron Overload Disorders and Polycythemia Vera

Therapeutic phlebotomy should be performed weekly (as tolerated) for patients with hemochromatosis and iron overload, with a target ferritin level of 50-100 μg/L. 1

Phlebotomy Protocol for Hemochromatosis

Initial Depletion Phase

• Remove 500 mL of blood weekly or biweekly 1
• Check hemoglobin/hematocrit prior to each procedure 1
• Ensure hemoglobin/hematocrit falls by no more than 20% of prior level 1
• Monitor serum ferritin every 10-12 phlebotomies 1
• Continue until serum ferritin reaches 50-100 μg/L 1

Maintenance Phase

• Continue phlebotomy at individualized intervals to maintain serum ferritin between 50-100 μg/L 1
• Frequency varies among individuals based on rate of iron reaccumulation 1
• Some patients require monthly phlebotomy while others may need only 1-2 units removed per year 1

Special Considerations for Different Conditions

Hereditary Hemochromatosis

• Proceed directly to phlebotomy without liver biopsy for C282Y homozygotes with elevated ferritin <1000 μg/L and normal liver enzymes 1
• For patients with end-organ damage due to iron overload, maintain the same phlebotomy targets 1
• Monitor for reaccumulation of iron and adjust maintenance schedule accordingly 1

Polycythemia Vera

• Phlebotomy is a cornerstone treatment for hematocrit control 2
• Unlike hemochromatosis, the goal is not to deplete iron but to control hematocrit
• Iron deficiency commonly develops in treated PV patients but does not appear to increase blood viscosity 3
• Consider that JAK inhibitors (ruxolitinib) may improve iron parameters in PV patients who have become iron deficient from frequent phlebotomies 2

Secondary Iron Overload

• Phlebotomy is indicated for certain forms of secondary iron overload, including porphyria cutanea tarda (PCT) 1
• For iron overload associated with ineffective erythropoiesis, iron chelation therapy is preferred over phlebotomy 1
• In chronic hepatitis C with mild iron overload (HIC <2500 μg/g dry weight), phlebotomy is not recommended 1

Patient Monitoring and Safety

Before Phlebotomy

• Assess hemoglobin/hematocrit levels 1
• For patients with severe iron overload, evaluate for cardiac involvement (ECG, echocardiography) 1
• For patients with juvenile hemochromatosis, investigate cardiac involvement with MRI 1

During Treatment Course

• Monitor for compliance, as studies show approximately 84% of patients comply with maintenance therapy in the first year, with a decline of about 6.8% annually 4
• C282Y homozygotes show better compliance with maintenance therapy compared to other patients 4
• Avoid vitamin C supplements during treatment as they can accelerate iron mobilization 1
• Avoid iron supplements and iron-fortified foods 1

Dietary Recommendations

• No strict dietary adjustments are necessary during treatment 1
• Limit red meat consumption 1
• Restrict alcohol intake, especially during iron depletion phase 1
• Consume fruit juices and citrus fruits in moderation, not with other foods 1
• Avoid raw or undercooked shellfish due to risk of Vibrio vulnificus infection in iron-loaded patients 1

Alternative Iron Removal Methods

Erythrocytapheresis

• Alternative to standard phlebotomy, especially during induction phase 1
• More cost-effective as fewer interventions are required 1
• Leads to more pronounced decrease in serum ferritin per treatment without larger decrease in serum hepcidin 5
• Hemoglobin levels remain more stable compared to phlebotomy 5

Iron Chelation Therapy

• Consider only if phlebotomy is not possible 1
• Deferasirox may be a second-line option but is not approved for hemochromatosis by European Medicines Agency 1
• Avoid in patients with advanced liver disease 1

Common Pitfalls and Caveats

1. Avoiding iron deficiency: Do not reduce ferritin below 50 μg/L to prevent iron deficiency 1
2. Cardiac complications: In patients with advanced disease, rapid iron mobilization may increase risk of sudden death due to cardiac arrhythmias 1
3. Compliance issues: Regular monitoring is essential as compliance with maintenance therapy decreases over time 4
4. Pregnancy considerations: In pregnant women with hemochromatosis, iron deficiency should be avoided, and phlebotomy may be paused during pregnancy 1
5. HCC surveillance: Patients with hemochromatosis and cirrhosis require HCC screening every 6 months, regardless of iron depletion status 1

By following these guidelines, phlebotomy can be safely and effectively used to manage iron overload disorders and polycythemia vera, reducing morbidity and mortality associated with these conditions.