At what hemoglobin (Hb) level and hematocrit (Hct) level is phlebotomy indicated?

Hemoglobin and Hematocrit Levels for Phlebotomy in Hemochromatosis

When performing phlebotomy for hemochromatosis, hemoglobin and hematocrit should be checked prior to each procedure, and should not be allowed to fall by more than 20% from the patient's baseline level. 1

Phlebotomy Protocol for Hemochromatosis

The American Association for the Study of Liver Diseases provides clear guidelines for phlebotomy in hemochromatosis:

Initial Therapeutic Phlebotomy

• Frequency: Weekly or biweekly removal of 500 mL of blood
• Pre-procedure monitoring: Check hemoglobin/hematocrit before each phlebotomy
• Safety threshold: Do not allow hemoglobin/hematocrit to fall by more than 20% of prior level
• Ferritin monitoring: Check serum ferritin every 10-12 phlebotomies
• Endpoint: Stop frequent phlebotomy when serum ferritin reaches 50-100 μg/L 1

Maintenance Phlebotomy

• Continue phlebotomy at intervals to maintain serum ferritin between 50-100 μg/L
• Continue to monitor hemoglobin/hematocrit before each procedure
• Maintain the same safety threshold (no more than 20% drop from baseline) 1

Important Considerations

Absolute Hemoglobin/Hematocrit Values

While the guidelines do not specify absolute cutoff values for hemoglobin or hematocrit, the 20% reduction rule provides a personalized safety threshold. For example:

• A patient with baseline hemoglobin of 15 g/dL should not drop below 12 g/dL
• A patient with baseline hematocrit of 45% should not drop below 36%

Monitoring for Complications

Patients with advanced disease (especially those with cardiac arrhythmias or cardiomyopathy) require careful monitoring as there is an increased risk of sudden death with rapid iron mobilization. This is due to intracellular iron in a toxic, low-molecular-weight chelate pool. 1

Polycythemia in Hemochromatosis

Interestingly, patients with hemochromatosis may have elevated hemoglobin and hematocrit levels. Research has shown median hemoglobin and hematocrit values of 15.5 g/dL and 44.9% respectively in C282Y/C282Y subjects, and even higher in other HFE mutations. 2 This elevated baseline should be considered when calculating the 20% reduction threshold.

Phlebotomy Response Patterns

The mean corpuscular volume (MCV) can be a useful additional parameter to monitor during phlebotomy therapy. During initial therapy, MCV typically increases transiently due to reticulocytosis, then stabilizes before decreasing more sharply when iron-limited erythropoiesis occurs. 3

Practical Application

1. Establish baseline hemoglobin and hematocrit before starting therapy
2. Calculate the 20% reduction threshold (baseline value × 0.8)
3. Check hemoglobin/hematocrit before each phlebotomy
4. If values approach the 20% reduction threshold, consider:
   • Extending the interval between phlebotomies
   • Reducing the volume of blood removed
   • Temporarily pausing therapy until values recover

Common Pitfalls to Avoid

• Vitamin C supplementation: Avoid in patients undergoing phlebotomy as it can accelerate iron mobilization to dangerous levels 1
• Iron supplementation: Should be avoided during treatment 1
• Relying solely on ferritin: While ferritin is important for determining when to stop frequent phlebotomy, hemoglobin/hematocrit monitoring is essential for safety during each procedure
• Fixed phlebotomy schedules: The frequency should be adjusted based on individual tolerance and laboratory parameters

By following these guidelines and carefully monitoring hemoglobin and hematocrit levels before each phlebotomy procedure, ensuring they do not fall by more than 20% from baseline, clinicians can safely and effectively manage iron overload in patients with hemochromatosis.