From the Guidelines
Patients with high ferritin levels should undergo therapeutic phlebotomy to reduce iron stores, as this treatment has been shown to improve survival, sense of well-being, and cardiac function, while also reducing the risk of hepatocellular carcinoma and other complications 1. High ferritin levels can be indicative of hemochromatosis (HH), a genetic disorder characterized by excessive iron absorption and storage in the body. According to the 2011 practice guideline by the American Association for the Study of Liver Diseases 1, phlebotomy remains the mainstay of treatment for HH, with the goal of reducing tissue iron stores to normal levels.
Key Benefits of Phlebotomy
- Improved survival if diagnosis and treatment are initiated before the development of cirrhosis and diabetes 1
- Improved sense of well-being and energy level 1
- Improved cardiac function 1
- Reduction in abdominal pain and skin pigmentation 1
- Normalization of elevated liver enzymes 1
- Reversal of hepatic fibrosis in approximately 30% of cases 1
Treatment Approach
The decision to treat HH with phlebotomy is straightforward for patients with evidence of liver disease or other end-organ manifestations 1. For patients with high ferritin levels but no symptoms or liver disease, treatment is often initiated due to its safety, efficacy, and potential societal benefits 1.
Phlebotomy Protocol
- One unit of blood (approximately 200-250 mg iron) should be removed once or twice per week as tolerated 1
- Hematocrit or hemoglobin should be measured before each phlebotomy to avoid reducing the hematocrit/hemoglobin to <80% of the starting value 1
- Serum ferritin analysis should be performed after every 10-12 phlebotomies (approximately 3 months) in the initial stages of treatment 1
- Phlebotomy can be stopped when iron stores are depleted, and the patient should be assessed for maintenance phlebotomy 1
From the Research
High Ferritin Levels
- High ferritin levels can be an indication of iron overload, which can be caused by various factors such as hereditary hemochromatosis, excessive alcohol consumption, or chronic liver disease 2.
- A study published in 2003 found that patient compliance with phlebotomy therapy for iron overload associated with hemochromatosis was high, with 96.6% of patients achieving iron depletion 3.
- However, another study published in 2024 noted that hyperferritinemia is a non-specific finding and can be caused by various factors, including acute phase reactions and reactive increases in ferritin due to underlying conditions 2, 4.
Diagnosis and Treatment
- The diagnosis of iron overload typically involves a combination of patient history, clinical features, and biochemical tests, including ferritin, transferrin saturation, and liver enzymes 2.
- Treatment options for iron overload include phlebotomy and chelation therapy, with phlebotomy being the initial treatment of choice in hereditary hemochromatosis 3, 5.
- A study published in 2015 found that deferasirox, an oral iron chelator, was effective in reducing iron burden in patients with hereditary hemochromatosis and could be a safe alternative to phlebotomy in selected patients 6.
Management of Hyperferritinemia
- An algorithm for the investigation of hyperferritinemia has been proposed, which involves determining the presence or absence of iron overload and identifying the underlying cause of hyperferritinemia 2, 4.
- Patients with ferritin levels below 1000 µg/L, normal transferrin saturation, and normal liver tests may not require further investigation and can be followed in primary care 2.
- However, patients with high ferritin levels and evidence of iron overload may require treatment with phlebotomy or chelation therapy to reduce their iron burden 3, 5, 6.