What is the recommended treatment approach for a patient diagnosed with hematomacrosis?

Treatment of Hemochromatosis (Haemochromatosis)

Patients with hemochromatosis and evidence of iron overload should undergo therapeutic phlebotomy as first-line treatment, with weekly bloodletting of 400-500 mL during the induction phase until serum ferritin reaches 50 μg/L, followed by maintenance phlebotomy every 1-4 months to maintain ferritin between 50-100 μg/L. 1

Induction Phase Treatment

Weekly or fortnightly phlebotomy is the cornerstone of initial therapy: 1

• Remove 400-500 mL of blood per session, adjusted for body weight and patient tolerance 1
• Continue until serum ferritin reaches 50 μg/L (but not lower to avoid iron deficiency) 1
• Monitor hemoglobin before each session 1
• If hemoglobin drops below 12 g/dL, decrease phlebotomy frequency 1
• If hemoglobin falls below 11 g/dL, discontinue phlebotomy temporarily and reassess 1

Erythrocytapheresis represents an alternative to standard phlebotomy, particularly cost-effective during induction as it requires fewer interventions. 1

Maintenance Phase Treatment

After achieving iron depletion, lifelong maintenance therapy prevents iron re-accumulation: 1

• Target serum ferritin: 50-100 μg/L 1
• Phlebotomy frequency: every 1-4 months depending on individual iron accumulation rate 1
• Average ferritin rises approximately 100 μg/L per year without treatment 1
• Patients without significant organ damage can serve as regular blood donors during maintenance 1

Critical Monitoring Parameters

Serum ferritin and hemoglobin must be monitored at each phlebotomy session to prevent both under-treatment and iron deficiency: 1

• Check hemoglobin at every bloodletting session 1
• Monitor ferritin to ensure target achievement and avoid overtreatment 1
• Ferritin below 20 μg/L significantly increases dietary iron absorption, indicating excessive depletion 1

Assessment of Liver Disease and Complications

All patients require non-invasive fibrosis assessment at diagnosis to guide treatment intensity and surveillance: 1

• Transient elastography with liver stiffness <6.4 kPa rules out advanced fibrosis 1
• Patients with ferritin <1,000 μg/L, normal transaminases, and no hepatomegaly have very low risk of advanced fibrosis 1
• Patients with cirrhosis (METAVIR F4) require HCC screening with abdominal ultrasound every 6 months regardless of iron depletion status 1
• Patients with advanced fibrosis (METAVIR F3) should also undergo HCC screening every 6 months 1

Cardiac Evaluation

Patients with severe iron overload require cardiac assessment due to risk of cardiomyopathy and arrhythmias: 1

• Perform ECG and echocardiography in all patients with severe overload 1
• Cardiac MRI for myocardial iron quantification is mandatory in juvenile hemochromatosis 1
• Iron removal therapy can prevent, improve, or even reverse cardiac dysfunction 1
• Conventional cardiology treatment should be initiated for heart failure and arrhythmias 1

Dietary Modifications

Specific dietary restrictions enhance treatment efficacy and prevent iron re-accumulation: 2, 3

• Avoid all vitamin C supplements during treatment, as pharmacologic doses accelerate iron mobilization and increase risk of cardiac complications and sudden death 2
• Avoid iron supplements and iron-fortified foods entirely 2, 3
• Limit red meat consumption 3
• Restrict alcohol intake, particularly during iron depletion phase 3
• Dietary vitamin C from foods requires only moderation, not elimination 2

Management of Specific Complications

Arthropathy affects 45-57% of patients and requires symptomatic management as phlebotomy does not reverse joint damage: 3

• NSAIDs and analgesics for pain control 3
• Joint replacement surgery ultimately required for end-stage disease 3
• Arthropathy can progress despite optimal iron management 3

Endocrine manifestations require targeted evaluation: 1

• Assess for diabetes mellitus 1
• Measure sex hormone concentrations for reproductive/sexual dysfunction 1
• Evaluate thyroid, adrenal, and parathyroid function when clinically indicated 1

Special Populations: Pregnancy

Iron deficiency must be avoided in pregnant patients with hemochromatosis: 1

• Achieve ferritin >45 μg/L before conception 1
• In mild to moderate iron overload without advanced liver disease, phlebotomy can be paused during pregnancy 1
• Normal pregnancy corresponds to iron requirement of approximately 500 mg 1
• Management is determined by liver disease stage and extrahepatic manifestations 1

Prognostic Impact of Treatment

Morbidity and mortality are significantly reduced when treatment begins before development of cirrhosis and diabetes. 1

• Phlebotomy improves survival in clinical and cohort studies 1
• Treatment may improve fatigue, arthralgias, and liver function tests 1
• Regression of liver fibrosis and cirrhosis occurs in a subset of patients 1
• Conclusive data on quality of life, liver cancer risk reduction, and cardiovascular disease impact remains limited 1

Common Pitfalls to Avoid

• Never supplement with vitamin C during active treatment—this poses serious cardiac risk 2
• Avoid excessive iron depletion (ferritin <50 μg/L during maintenance) which increases iron absorption 1
• Do not neglect HCC surveillance in cirrhotic patients even after successful iron depletion 1
• Monitor vitamin B12 and folate in patients requiring frequent phlebotomies to prevent macrocytic anemia 4