From the Guidelines
In hereditary hemochromatosis (HH), transferrin levels are typically normal to low, while transferrin saturation is elevated, usually above 45% in men and above 50% in women, as indicated by the most recent guidelines 1. The pattern of normal to low transferrin levels with elevated transferrin saturation occurs because hemochromatosis causes excessive iron absorption, leading to increased serum iron that binds to available transferrin. As iron accumulates, the transferrin protein becomes increasingly saturated with iron, but the total amount of transferrin itself doesn't increase and may even decrease due to negative feedback mechanisms. Some key points to consider in the diagnosis of hereditary hemochromatosis include:
- Transferrin saturation percentage is a more valuable diagnostic marker than the absolute transferrin level, and it often becomes elevated before other abnormalities appear, as seen in studies such as 1.
- Transferrin saturation, along with serum ferritin levels, is used as an initial screening test for hemochromatosis.
- Patients with hemochromatosis typically show normal to low transferrin levels with high transferrin saturation, high serum iron, and elevated ferritin levels, reflecting the body's iron overload state.
- Genetic testing for HFE gene mutations (particularly C282Y and H63D) is necessary to confirm hereditary hemochromatosis after these initial biochemical abnormalities are detected, as recommended by recent guidelines 1. The most recent guidelines from the European Association for the Study of the Liver 1 provide a comprehensive approach to the diagnosis and management of hemochromatosis, emphasizing the importance of early diagnosis and treatment to prevent complications such as cirrhosis, hepatocellular carcinoma, and other end-organ damage.
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.