Latest Ferritin Recommendations for Phlebotomy in Hemochromatosis
The most recent 2022 EASL guidelines recommend targeting a serum ferritin of 50 μg/L during the induction phase and maintaining 50-100 μg/L during the maintenance phase, with phlebotomy performed weekly or biweekly initially, then 2-6 times yearly for life. 1
Induction Phase Protocol
Target ferritin: 50 μg/L 1
- Perform phlebotomy weekly or biweekly, removing 400-500 mL per session (approximately 200-250 mg of iron removed per unit) 1
- Check hemoglobin before every phlebotomy session 1
- Monitor ferritin after every 4 phlebotomies until ferritin reaches 200 μg/L, then check every 1-2 treatment sessions 1
- Continue induction until target ferritin of 50 μg/L is achieved 1
The 2022 EASL guidelines represent an evolution from older recommendations. The 2011 AASLD guidelines suggested a slightly broader target of 50-100 μg/L even during induction 1, but the more recent European guidance emphasizes the lower end (50 μg/L) to ensure adequate iron depletion while avoiding iatrogenic iron deficiency 1, 2.
Maintenance Phase Protocol
Target ferritin: 50-100 μg/L 1
- Perform phlebotomy at variable frequency, typically 2-6 times per year depending on individual iron reaccumulation rates 1
- Check hemoglobin before each phlebotomy session 1
- Monitor ferritin and transferrin saturation every 6 months 1
- Continue lifelong follow-up 1
This maintenance range of 50-100 μg/L represents consensus between both American and European guidelines 1, providing a buffer against both iron reaccumulation and iatrogenic iron deficiency.
Critical Monitoring Parameters
Hemoglobin monitoring is mandatory before every single phlebotomy session to prevent excessive anemia and symptomatic iron deficiency 1, 3. Research has documented cases where inadequate monitoring led to sustained iron deficiency lasting over 2 years, causing significant morbidity 3.
Ferritin monitoring frequency should be adjusted based on treatment phase:
- During induction: after every 4 phlebotomies until 200 μg/L reached, then every 1-2 sessions 1
- During maintenance: every 6 months 1
Special Populations and Adjusted Targets
Elderly patients may benefit from more relaxed maintenance targets of <200 μg/L for women and <300 μg/L for men 2, 4, though this represents expert opinion rather than high-level guideline recommendations.
Patients with cardiac involvement (cardiomyopathy or arrhythmias) require special caution as rapid iron mobilization increases risk of sudden death 2, 5, 6. These patients may need slower phlebotomy schedules or consideration of iron chelation therapy instead 6.
Patients with severe anemia or decompensated heart failure cannot undergo phlebotomy and require iron chelation as second-line therapy 1, 6.
Critical Pitfalls to Avoid
Never target ferritin below 50 μg/L as this increases risk of symptomatic iron deficiency without additional clinical benefit 1, 2. Older literature from 1998 suggested targeting 10-20 μg/L during induction 7, but this approach has been abandoned due to excessive complications 3.
Avoid vitamin C supplements entirely, especially during active iron depletion, as vitamin C accelerates iron mobilization and increases oxidative stress 1, 2, 5. This is a consistent recommendation across all guidelines.
Do not perform phlebotomy without checking hemoglobin first 1. The development of unexplained anemia or reduced phlebotomy requirements during treatment should trigger evaluation for alternative causes including gastrointestinal bleeding 1.
Dietary iron restriction is unnecessary and should not be emphasized as it does not substitute for iron removal therapy 1. However, patients should avoid medicinal iron supplements, daily red meat consumption, and moderate-to-heavy alcohol intake 1.
Alternative Treatment Considerations
Erythrocytapheresis is an acceptable alternative when available, with the same ferritin targets of 50 μg/L for induction and 50-100 μg/L for maintenance 1. This modality removes more iron per session (up to 1000 mL erythrocytes vs. 250 mL with phlebotomy), reducing total number of procedures by approximately 70% 8, 9, though with higher per-session costs 1.
Iron chelation therapy (deferasirox) is reserved for patients who cannot tolerate phlebotomy, requires careful risk-benefit assessment, and targets higher ferritin levels than phlebotomy 1. It should not be used in patients with advanced liver disease 1.