What is the transferrin level in hereditary hemochromatosis (HH)?

From the Guidelines

In hereditary hemochromatosis (HH), transferrin levels are typically normal to low, while transferrin saturation is elevated, usually above 45% or 50% in men and post-menopausal women, and above 45% in females 1.

Key Points to Consider

• The diagnostic laboratory findings in hemochromatosis typically include elevated serum ferritin, elevated serum iron, and increased transferrin saturation, rather than changes in total transferrin concentration itself.
• The genetic mutations in hemochromatosis, most commonly HFE gene mutations, affect iron regulatory mechanisms, causing inappropriate iron absorption regardless of body iron stores.
• When evaluating a patient for hemochromatosis, it's crucial to measure transferrin saturation rather than just transferrin levels, as the saturation percentage provides more diagnostic value for this condition.

Important Considerations for Diagnosis and Treatment

• Provisional iron overload based on serum iron parameters (TSAT >45% and ferritin >200 µg/L in females and TSAT >50% and ferritin >300 µg/L in males and post-menopausal women) is sufficient to diagnose haemochromatosis in patients homozygous for p.Cys282Tyr in HFE 1.
• Treatment targets for phlebotomy are ferritin <50 µg/L during the induction phase and <100 µg/L during the maintenance phase, as recommended by the European Association for the Study of the Liver 1.

Clinical Implications

• Early diagnosis and treatment by phlebotomy can prevent cirrhosis, hepatocellular carcinoma, diabetes, arthropathy, and other complications associated with hemochromatosis.
• The stage of liver fibrosis and other end-organ damage should be carefully assessed at diagnosis because they determine disease management, and patients with advanced fibrosis should be included in a screening program for hepatocellular carcinoma 1.

From the Research

Transferrin Level in Hereditary Hemochromatosis (HH)

• The transferrin saturation level is a key indicator in the diagnosis and management of hereditary hemochromatosis (HH) 2, 3, 4, 5, 6.
• Studies have shown that patients with HH often have increased transferrin saturation levels, which can lead to iron overload and tissue damage 2, 3, 4, 5.
• The goal of treatment for HH is to reduce iron stores and maintain a transferrin saturation level below 70% 3, 4, 5, 6.
• Phlebotomy is a common treatment for HH, but it may not be suitable for all patients, and alternative treatments such as erythrocytapheresis may be considered 2, 3.
• The duration of exposure to increased transferrin saturation during maintenance therapy has been associated with worse outcomes, including more severe general and joint symptoms 4.

Transferrin Saturation Targets

• A transferrin saturation level of <70% is considered a safe target for patients with HH 3, 4, 5.
• Patients who achieve this target sooner, such as those treated with erythrocytapheresis, may have better outcomes than those who take longer to reach this target 3.
• Maintenance of serum ferritin levels at 50 μg/L or less does not necessarily indicate control of transferrin saturation, and guidelines on the management of HH may need to be revised to reflect this 4.

Diagnosis and Management

• Hereditary hemochromatosis can be diagnosed through laboratory testing for serum ferritin and transferrin saturation, as well as genetic testing for the HFE mutation 2, 6.
• Treatment of HH typically involves phlebotomy to remove excess iron stores, but alternative treatments such as erythrocytapheresis may be considered in certain cases 2, 3, 6.
• Optimal care for patients with HH requires careful monitoring of transferrin saturation levels and adjustment of treatment as needed to maintain a safe target level 5, 6.