Treatment Plan for Hemochromatosis
First-Line Treatment: Therapeutic Phlebotomy
Patients with confirmed hemochromatosis and evidence of iron overload should undergo therapeutic phlebotomy as first-line treatment, consisting of an induction phase followed by lifelong maintenance therapy. 1
Induction Phase Protocol
- Remove 450-500 mL of blood weekly or biweekly until serum ferritin reaches the target of 50 μg/L 1, 2
- Check hemoglobin/hematocrit before each phlebotomy session to prevent excessive anemia 1, 2
- Monitor serum ferritin after every 4 phlebotomies until it reaches 200 μg/L, then check every 1-2 treatment sessions 1
- Continue induction until ferritin reaches 50 μg/L (not lower, to avoid iron deficiency) 1
Maintenance Phase Protocol
- Continue phlebotomy at individualized intervals (typically 2-6 sessions per year) to maintain ferritin between 50-100 μg/L 1, 3
- Monitor ferritin and transferrin saturation every 6 months during stable maintenance 1, 4
- Check hemoglobin before each maintenance phlebotomy 1
- Lifelong follow-up is mandatory 1
The evidence strongly supports phlebotomy's ability to improve survival, reduce morbidity, and potentially reverse liver fibrosis in patients treated before cirrhosis develops 1. Treatment initiated before cirrhosis and diabetes significantly reduces mortality 1.
Alternative Treatment: Erythrocytapheresis
Erythrocytapheresis represents the preferred treatment option in selected cases where available, particularly during the induction phase 1
- Removes up to 1000 mL of red blood cells per session (versus 250 mL with standard phlebotomy) 5, 6
- Requires fewer procedures and shorter treatment duration in the induction phase 1, 5
- Personalized erythrocytapheresis (based on sex, body weight, total blood volume, and hematocrit) is cost-effective compared to fixed-volume approaches 1
- Causes fewer hemodynamic changes compared to phlebotomy 1
- Mild citrate reactions are common but manageable 1
- Target ferritin goals remain the same: 50 μg/L for induction, 50-100 μg/L for maintenance 1
Erythrocytapheresis can remove excess iron twice as fast as manual phlebotomy, achieving iron depletion in approximately 6.7 months with excellent tolerability 5.
Second-Line Treatment: Iron Chelation Therapy
Iron chelation should only be considered when phlebotomy is not possible, after careful risk-benefit assessment by a specialist 1, 3
Deferasirox (Oral Chelator)
- Most studied chelation option for hemochromatosis, though not FDA-approved for this indication 1
- Contraindicated in patients with advanced liver disease (Child-Pugh C) 1, 7
- Black box warnings include renal failure, hepatic failure, and gastrointestinal hemorrhage 7
- Requires intensive monitoring:
- Common adverse effects include GI symptoms and renal impairment 1, 7
Deferoxamine (Subcutaneous)
- Traditional chelation option at 20-40 mg/kg/day subcutaneously 2
- May be necessary in severe juvenile hemochromatosis, especially during induction 1
- Combination therapy with phlebotomy/erythrocytapheresis is possible 1
Critical caveat: Target ferritin with chelation therapy is higher than with phlebotomy/erythrocytapheresis 1. Chelation carries significantly more adverse effects and monitoring burden compared to phlebotomy 7.
Dietary and Lifestyle Modifications
Dietary modifications do not substitute for iron removal therapy but are important adjuncts 1
Mandatory Restrictions
- Avoid iron supplements and iron-fortified foods entirely 1, 4, 3
- Avoid supplemental vitamin C, especially during active iron depletion, as it accelerates iron mobilization and increases oxidative stress 1, 2, 4
- Limit red meat consumption 1, 3
- Restrict alcohol intake during iron depletion phase; patients with cirrhosis must abstain completely 1, 3
Infection Prevention
- Avoid raw or undercooked shellfish due to risk of Vibrio vulnificus infection, which is particularly dangerous in iron-overloaded patients 1
- Avoid contact of wounds with seawater for the same reason 1
Additional Considerations
- Consume fruit juices and citrus fruits in moderation, not combined with other foods 1
- Proton pump inhibitors (when prescribed for other indications) can reduce phlebotomy requirements 1
Monitoring Parameters and Safety
Pre-Treatment Assessment
Before initiating therapy, obtain 2, 3:
- Serum ferritin to quantify iron burden
- Liver function tests to assess hepatic involvement
- Complete blood count to ensure adequate hemoglobin for phlebotomy
- Renal function to establish baseline
- Baseline auditory and ophthalmic examinations 1
During Treatment Monitoring
- Hemoglobin/hematocrit before each phlebotomy 1, 2
- Serum ferritin monthly to assess response and prevent overchelation 2, 3
- Liver function tests periodically 2
- Investigate any unexpected reduction in phlebotomy need, as this may indicate occult bleeding, malignancy, or other pathology 1
Special Populations and Critical Warnings
Overchelation Risk
Overchelation represents a serious and potentially fatal complication, particularly in pediatric patients 1, 7
- If ferritin falls below 1000 μg/L on 2 consecutive visits, consider dose reduction, especially if receiving >17.5 mg/kg/day deferasirox equivalent 1, 3
- If ferritin falls below 500 μg/L, interrupt therapy and continue monthly monitoring 7
- Pediatric patients receiving deferasirox at doses >17.5 mg/kg/day when ferritin <1000 μg/L have higher rates of renal adverse events 7
- Continued administration when body iron burden approaches normal range can result in life-threatening adverse events 7
Pregnancy Considerations
- Avoid iron deficiency in patients planning pregnancy 1
- In pregnant women with mild-moderate iron overload without advanced liver disease, phlebotomy can be paused for the duration of pregnancy in most patients 1
- Management is determined by liver disease stage and extrahepatic manifestations 1
Elderly Patients
- Deferasirox has been associated with serious and fatal adverse reactions predominantly in elderly patients 7
- Monitor elderly patients more frequently for toxicity 7
Patients with Cardiomyopathy
- Rapid iron mobilization increases risk of sudden death in patients with cardiac involvement 2
- Consider slower phlebotomy schedule or iron chelation in these cases 2
Blood Donation Considerations
Patients with uncomplicated hemochromatosis (without significant organ damage) can be accepted as regular blood donors during the maintenance phase 1
- Blood from hemochromatosis patients should be made available for transfusion when possible 1
- Individuals at risk (at-risk genotypes with elevated transferrin saturation but normal ferritin) may be encouraged to volunteer as regular blood donors 1
- Patients must continue routine monitoring through their hemochromatosis service even when donating blood 1
Prognostic Considerations
Morbidity and mortality are significantly reduced when treatment is initiated before the development of cirrhosis and/or diabetes 1. Phlebotomy therapy has demonstrated improved survival in clinical and cohort studies 1, 3. However, in patients with advanced cirrhosis, iron removal does not reverse the condition, and liver transplantation may be required for decompensated disease 3. Advanced fibrosis is modified by additional risk factors including alcohol consumption, type 2 diabetes, and viral hepatitis, though validated HCC risk scores are not available for tailored surveillance 1.