From the Guidelines
Haemochromatosis with low ferritin does not require immediate therapeutic phlebotomy, and instead, patients should undergo evaluation for causes of iron deficiency and regular monitoring of ferritin levels every 3-6 months. In the context of haemochromatosis, low ferritin levels are unusual and may indicate early disease, blood loss, or another concurrent condition affecting iron levels 1. According to the EASL clinical practice guidelines on haemochromatosis 1, the target for iron depletion during the induction phase is a serum ferritin of 50 μg/L, but not lower to avoid iron deficiency. However, for patients with confirmed haemochromatosis genetic mutations but low ferritin, no therapeutic phlebotomy is indicated until ferritin levels rise above the normal range. Some key points to consider in managing haemochromatosis with low ferritin include:
- Evaluating for causes of iron deficiency such as gastrointestinal bleeding, menstrual blood loss, malabsorption, or dietary insufficiency 1
- Regular monitoring of ferritin levels every 3-6 months to detect when iron loading begins 1
- Treating any identified cause of iron deficiency while continuing to monitor iron parameters 1
- Initiating standard haemochromatosis management with therapeutic phlebotomy once ferritin levels begin to rise above normal, aiming to maintain ferritin in the low-normal range 1. It is also important to monitor serum haemoglobin during both induction and maintenance phases, and adjust the frequency of phlebotomy accordingly 1. Additionally, periodic checks of plasma folate and plasma cobalamin are recommended, especially in patients who require numerous venesections 1.
From the Research
Haemochromatosis with Low Ferritin
- Haemochromatosis is a genetic disorder characterized by excessive iron absorption, leading to iron overload and potential organ damage 2, 3, 4.
- The diagnosis of haemochromatosis is typically based on elevated serum ferritin levels and transferrin saturation, as well as genetic testing for HFE gene mutations 3, 5, 6.
- However, low ferritin levels in patients with haemochromatosis can pose a diagnostic challenge, as ferritin levels can be influenced by various factors such as inflammation, liver disease, and other iron overload syndromes 2, 6.
- Studies have shown that patients with HFE gene mutations, particularly C282Y homozygotes, can have abnormal transferrin saturation and serum ferritin values, but penetrance can be incomplete, and some individuals may have normal or low ferritin levels despite having the mutation 5, 6.
- In cases where ferritin levels are low, other diagnostic approaches such as genetic testing, liver biopsy, and magnetic resonance imaging (MRI) may be necessary to confirm the diagnosis of haemochromatosis 3, 4.
Diagnostic Considerations
- Serum ferritin measurement is a useful prognostic indicator of disease severity, but it is not always elevated in patients with haemochromatosis 3, 5.
- Transferrin saturation is also an important diagnostic parameter, but it can be influenced by factors such as iron deficiency and inflammation 5.
- Genetic testing for HFE gene mutations can help confirm the diagnosis of haemochromatosis, but it is not always necessary, and other diagnostic approaches may be sufficient 3, 6.
- Liver biopsy may be necessary to stage the degree of fibrosis and diagnose non-classical hereditary hemochromatosis in patients with other genetic defects 3.
Management and Treatment
- Phlebotomy is the first-line treatment for haemochromatosis, and it is guided by serial measurements of serum ferritin levels and transferrin saturation 3, 4.
- Dietary modification is generally unnecessary, but a healthy, well-balanced diet is recommended as part of the ongoing management of the disease 4.
- Iron avidity can result from overtreatment, and it may mimic undertreatment with persistently elevated transferrin saturation 3.