Primary Treatment for Hemochromatosis
Therapeutic phlebotomy is the first-line and mainstay treatment for hemochromatosis, which significantly reduces morbidity and mortality when initiated before the development of cirrhosis and diabetes. 1, 2
Treatment Indications and Goals
Initiate phlebotomy in all patients with evidence of iron overload, including asymptomatic individuals with homozygous hemochromatosis and elevated iron markers, as well as symptomatic patients to prevent progression of organ damage. 1
Treatment should begin when patients have transfused at least 100 mL/kg of packed red blood cells (approximately 20 units for a 40 kg person) and serum ferritin consistently exceeds 1000 mcg/L. 3
The primary goal is to deplete iron stores to a target serum ferritin of 50-100 μg/L, which eliminates the risk of hepatocellular carcinoma (HCC) if achieved before cirrhosis develops. 1, 2
Induction Phase Protocol
Remove one unit of blood (450-500 mL) containing approximately 200-250 mg of iron once or twice weekly as tolerated. 1, 2
Check hemoglobin or hematocrit before each phlebotomy session and avoid reducing these values to less than 80% of baseline. 1
Monitor serum ferritin every 10-12 phlebotomies (approximately every 3 months) during initial treatment, then more frequently as levels approach the target range of 50-100 μg/L. 1, 2
Iron depletion may require 2-3 years in patients with total body iron stores exceeding 30 grams. 1
Maintenance Phase
After achieving target ferritin levels, assess whether maintenance phlebotomy is needed, as not all patients reaccumulate iron at the same rate. 1
Maintain serum ferritin between 50-100 μg/L through periodic phlebotomy, with frequency varying from 3-4 times yearly for men to 1-2 times yearly for women. 2, 4
Avoid inducing iron deficiency, which can cause symptomatic anemia, microcytosis, and hypochromia that may persist for months. 1, 5
Expected Clinical Outcomes
Symptoms that respond well to phlebotomy include: 1
- Malaise and fatigue
- Skin pigmentation
- Abdominal pain
- Improved insulin requirements in diabetics
- Improved cardiac function
Symptoms with limited or no response include: 1
Arthropathy (less responsive)
Hypogonadism (less responsive)
Advanced cirrhosis (no response)
Testicular atrophy (no reversal)
Hepatic fibrosis reverses in approximately 30% of cases with phlebotomy, but established cirrhosis does not reverse. 1, 6
Survival improves to normal population levels when treatment begins before cirrhosis and diabetes develop. 1, 4
Alternative Treatment: Iron Chelation
Iron chelation therapy with deferasirox is reserved as second-line treatment when phlebotomy is contraindicated due to severe anemia, hemodynamic instability, or inability to tolerate blood removal. 2, 4
Deferasirox is not FDA-approved for hemochromatosis and should be avoided in patients with advanced liver disease (Child-Pugh C) or eGFR less than 40 mL/min/1.73 m². 2, 3
Deferoxamine can be administered at 40 mg/kg/day subcutaneously over 8-12 hours nightly, 5-7 nights weekly, for patients requiring chelation. 4
Dietary and Lifestyle Modifications
Avoid all iron supplements, iron-fortified foods (including breakfast cereals), and multivitamins containing iron. 2, 4, 7
Limit vitamin C supplementation to ≤500 mg/day, as vitamin C enhances iron absorption. 2, 4, 7
Restrict alcohol intake during iron depletion; patients with cirrhosis must completely abstain from alcohol. 2, 6, 7
Avoid raw or undercooked shellfish due to risk of fatal Vibrio vulnificus infection, particularly in patients with liver disease. 2, 4, 7
Minimize red meat consumption but maintain a broadly healthy diet without strict iron restriction. 4, 7
Critical Monitoring Requirements
Patients with cirrhosis require lifelong HCC screening every 6 months even after successful iron depletion, as HCC accounts for 30% of hemochromatosis-related deaths and complications of cirrhosis account for an additional 20%. 1, 2
Monitor liver function tests regularly, as elevated transaminases normalize with successful phlebotomy. 1, 6
Obtain baseline auditory and ophthalmic examinations before initiating any chelation therapy. 6, 3
Common Pitfalls to Avoid
Do not delay treatment in asymptomatic patients with confirmed iron overload, as early intervention prevents irreversible organ damage including cirrhosis and HCC. 1
Do not continue aggressive phlebotomy once ferritin falls below 50 μg/L, as this causes symptomatic iron deficiency that may require months to resolve even without iron supplementation. 1, 5
Do not discontinue HCC surveillance after achieving iron depletion in cirrhotic patients, as the risk of HCC persists despite normalization of iron stores. 1, 2
Recognize that transferrin saturation remains elevated until iron stores are depleted, while ferritin progressively falls and reflects depletion of iron stores. 1