From the Guidelines
High ferritin levels combined with low Total Iron Binding Capacity (TIBC) typically indicate iron overload or hemochromatosis, and the most effective treatment is therapeutic phlebotomy, as recommended by the 2022 EASL clinical practice guidelines on haemochromatosis 1. This pattern suggests that the body has excess iron stores, with ferritin serving as the primary storage protein for iron. When ferritin is elevated while TIBC is low, the body is signaling that it has sufficient or excessive iron and is reducing its capacity to bind additional iron in the bloodstream. Some key points to consider in the management of iron overload include:
- Therapeutic phlebotomy is the mainstay of treatment for hereditary hemochromatosis (HH) and can help reduce tissue iron stores to normal, improve survival, and improve quality of life 1.
- MRI can be helpful for detection, non-invasive quantification of iron, and to study the distribution of iron in the liver, spleen, pancreas, heart, and brain in patients with suspicion or diagnosis of iron overload disorder 1.
- Serum iron parameters, such as transferrin saturation and ferritin, are surrogates of body iron status, but are not always sufficient to ascertain iron overload, and should be used in conjunction with other diagnostic tools 1.
- Early diagnosis and management are crucial to prevent organ damage, particularly affecting the liver, heart, and pancreas, and to improve morbidity, mortality, and quality of life. Some important considerations in the treatment of iron overload include:
- The frequency of phlebotomy varies among individuals, due to the variable rate of iron accumulation in HH, and some patients may require maintenance phlebotomy monthly, while others may need only 1-2 units of blood removed per year 1.
- Supplemental vitamin C should be avoided by iron-loaded patients, particularly those undergoing phlebotomy, as it can accelerate mobilization of iron and increase pro-oxidant and/or free radical activity 1.
- No dietary adjustments are necessary, as the amount of iron absorption that an individual can affect with a low-iron diet is small (2-4 mg/day) 1.
From the Research
Ferritin High and TIBC Low
- Elevated ferritin levels can indicate iron overload, which may be associated with hereditary hemochromatosis 2, 3, 4.
- Transferrin saturation and serum ferritin level are commonly used to diagnose hereditary hemochromatosis, with ferritin levels greater than 300 ng per mL for men and 200 ng per mL for women being highly suggestive of the condition 3.
- A low TIBC (Total Iron-Binding Capacity) can also be an indicator of iron overload, as it suggests that the body's iron-binding capacity is saturated 5.
- Hereditary hemochromatosis is an autosomal recessive disorder that disrupts iron homeostasis, resulting in systemic iron overload, and can lead to damage to organs such as the liver, pancreas, joints, heart, skin, and pituitary gland 3.
- Phlebotomy is the mainstay of treatment for hereditary hemochromatosis and can help improve heart function, reduce abnormal skin pigmentation, and lessen the risk of liver complications 2, 3, 4.
Diagnostic Considerations
- The use of ferritin as a diagnostic test of iron deficiency and overload is a common clinical practice, but its levels can be elevated in inflammation and infection 5.
- The diagnostic accuracy of ferritin concentrations for detecting iron deficiency and risk of iron overload is influenced by factors such as age, sex, and clinical status 5.
- Genetic testing for the HFE mutation can be performed in patients with elevated iron indices and a suspicion for hemochromatosis or liver disease 4.
Treatment and Management
- Early detection and treatment of hereditary hemochromatosis can prevent manifestations of the disease, and skin pigmentation and some cardiac damage may reverse on depletion of iron stores 2, 3.
- Phlebotomy is a relatively safe and efficacious treatment for hereditary hemochromatosis, but the benefits of screening primary care patients are not well established 6.