What is phlebotomy and what are its indications?

What is Phlebotomy and Its Indications

Phlebotomy is the therapeutic removal of blood from the body, primarily indicated for managing iron overload disorders such as hemochromatosis, polycythemia vera, porphyria cutanea tarda, and certain cases of secondary iron overload. 1, 2

Definition and Mechanism

Phlebotomy involves removing whole blood (typically 400-500 mL per session) to reduce iron burden or red blood cell mass. 1 Each unit of blood removed contains approximately 200-250 mg of iron, making it the most efficient method for iron depletion. 1, 3

Primary Indications

Hemochromatosis (Primary Indication)

• Patients with HFE hemochromatosis and evidence of iron overload should undergo therapeutic phlebotomy as first-line treatment. 1, 4
• C282Y homozygotes with elevated ferritin should proceed directly to phlebotomy without liver biopsy if ferritin is <1000 μg/L and liver enzymes are normal. 1
• Treatment is indicated even in patients with advanced fibrosis or cirrhosis. 1
• Patients with end-organ damage from iron overload require regular phlebotomy to the same endpoints. 1

Secondary Iron Overload

• Porphyria cutanea tarda (PCT): Phlebotomy is clearly indicated and results in reduction of skin manifestations. 1
• Non-alcoholic fatty liver disease (NAFLD): Studies demonstrate benefit with improvement in insulin resistance parameters and reduction in elevated ALT levels. 1, 2
• Chronic hepatitis C: Phlebotomy reduces ALT levels and achieves marginal histopathologic improvement, though it has no effect on viral clearance. 1
• Alcoholic liver disease (ALD): No published evidence supports phlebotomy benefit; not recommended. 1

Polycythemia Vera

• Indicated for managing elevated red blood cell mass and reducing thrombotic risk. 2

Other Conditions

• Sickle cell disease (in specific circumstances). 2
• Iron overload after allogeneic hematopoietic cell transplantation. 5

Treatment Protocol

Induction Phase

• Remove 500 mL of blood weekly or biweekly as tolerated during initial iron depletion. 1, 3, 6
• Check hemoglobin/hematocrit before each session; do not allow hemoglobin to fall below 80% of starting value. 3, 4
• Monitor serum ferritin every 10-12 phlebotomies (approximately every 3 months). 3, 6
• Target ferritin level: 50-100 μg/L. 1, 3
• This phase may take 2-3 years for patients with significant iron overload (>30g total body iron). 3

Maintenance Phase

• Continue phlebotomy at individualized intervals (typically every 1-4 months) to maintain ferritin between 50-100 μg/L. 3, 6
• Monitor ferritin every 6 months during maintenance. 3
• Average ferritin rises approximately 100 μg/L per year without treatment, necessitating lifelong maintenance. 3, 4

Critical Monitoring Parameters

• Hemoglobin/hematocrit before each phlebotomy session. 3, 6
• If hemoglobin falls below 12 g/dL, decrease phlebotomy frequency. 3
• Serum ferritin to assess iron depletion progress and maintain target range. 3, 6
• Liver function tests periodically to assess hepatic complications. 6

Important Contraindications and Precautions

Dietary Modifications

• Avoid vitamin C supplements entirely, especially during active iron depletion, as vitamin C accelerates iron mobilization to potentially dangerous levels. 1, 3, 6
• Avoid iron supplements and iron-fortified foods. 4
• Dietary adjustments are generally unnecessary since dietary iron absorption (2-4 mg/day) is minimal compared to phlebotomy removal (200-250 mg/unit). 3, 6
• Avoid raw or undercooked shellfish due to Vibrio vulnificus infection risk. 1

Special Populations

• Patients with cardiac arrhythmias or cardiomyopathy require careful monitoring due to increased risk of sudden death with rapid iron mobilization; consider slower phlebotomy schedule. 3, 6
• Patients with advanced disease who poorly tolerate classical phlebotomies may require personalized mini-phlebotomies plus subcutaneous deferoxamine infusion. 1
• Consider more relaxed ferritin targets in elderly patients (up to 200 μg/L for women, 300 μg/L for men). 6

Alternative Treatments When Phlebotomy Not Tolerated

• Deferoxamine (DFO): 20-40 mg/kg/day subcutaneously is the traditional chelation option. 1, 6
• Deferasirox (DFX): Most studied oral chelator at 10-15 mg/kg dose, though not approved for hemochromatosis by European Medicines Agency and should not be used in advanced liver disease. 1, 4
• Deferiprone (DFP): Very limited experience; risk of haematological toxicity including agranulocytosis. 1
• Iron chelation is second-line therapy only when phlebotomy is contraindicated or not tolerated. 4

Common Pitfalls to Avoid

• Do not perform phlebotomy too rapidly in patients with cardiac disease—this increases sudden death risk. 3, 6
• Do not allow hemoglobin to drop excessively; maintain above 80% of baseline. 3
• Do not recommend dietary iron restriction as primary therapy—the impact is negligible compared to phlebotomy. 3, 6
• Do not use vitamin C supplements during treatment—this can cause dangerous iron mobilization. 1, 3, 6
• Ensure adequate hydration before and after treatment, and avoid vigorous physical activity for 24 hours post-phlebotomy. 1