What is the treatment for elevated ferritin levels (Hyperferritinemia) and low transferrin levels (Hypotransferrinemia)?

From the Guidelines

Treatment for elevated ferritin levels and low transferrin levels should focus on determining the underlying cause of iron overload and addressing it appropriately, with therapeutic phlebotomy being the primary treatment, aiming to reduce ferritin levels to 50-100 ng/mL, as recommended by the most recent guidelines 1.

Key Considerations

• The first step is consulting with a healthcare provider for proper evaluation, which typically includes additional blood tests like complete iron studies, liver function tests, and possibly genetic testing for hereditary hemochromatosis.
• If iron overload is confirmed, therapeutic phlebotomy is often the primary treatment, typically removing one unit of blood (about 500 mL) weekly until ferritin levels decrease to 50-100 ng/mL, followed by maintenance phlebotomies every 2-4 months.
• For those who cannot tolerate phlebotomy, iron chelation therapy with medications like deferasirox (Exjade, Jadenu) or deferoxamine (Desferal) may be prescribed.
• Dietary modifications are also important, including limiting alcohol consumption, avoiding iron supplements and vitamin C with meals, and reducing intake of red meat and iron-fortified foods.

Monitoring and Maintenance

• Serum ferritin should be monitored every 6 months to adapt the treatment schedule and ensure that ferritin remains within the target range.
• Serum haemoglobin should always be monitored during both induction and maintenance phases, at the time of each bloodletting session.
• If haemoglobin concentrations are <12 g/dl, the frequency of phlebotomy should be decreased and in specific cases a reduction in volume should be considered.
• Plasma folate and plasma cobalamin should be periodically checked, especially in patients who require numerous venesections; if necessary, vitamin supplements should be administered.

Underlying Cause

• Elevated ferritin levels with low transferrin suggest potential hemochromatosis or inflammation, as transferrin typically decreases when iron stores are high or during inflammatory conditions, making proper diagnosis crucial before initiating treatment.
• The most recent guidelines recommend a target serum ferritin level of 50-100 lg/L for patients with haemochromatosis, with a more relaxed target range of <200 lg/L for women and <300 lg/L for men during the maintenance phase 1.

From the FDA Drug Label

Deferasirox tablets are contraindicated in patients with platelet counts below 50 x 10^9/L. If the serum ferritin falls below 1000 mcg/L at 2 consecutive visits, consider dose reduction, especially if the deferasirox tablets dose is greater than 17.5 mg/kg/day If the serum ferritin falls below 500 mcg/L, interrupt therapy with deferasirox tablets and continue monthly monitoring.

The treatment for elevated ferritin levels (Hyperferritinemia) is iron chelation therapy with deferasirox tablets, with a goal to reduce serum ferritin levels to a target range.

• The dose of deferasirox should be adjusted based on serum ferritin levels, with consideration of dose reduction if serum ferritin falls below 1000 mcg/L at 2 consecutive visits.
• Therapy should be interrupted if serum ferritin falls below 500 mcg/L. However, low transferrin levels (Hypotransferrinemia) are not directly addressed in the provided drug labels 2 3.

From the Research

Treatment for Elevated Ferritin Levels (Hyperferritinemia) and Low Transferrin Levels (Hypotransferrinemia)

• The treatment for hyperferritinemia depends on the underlying cause, which can be determined through patient history, clinical features, and biochemical tests 4.
• In cases of iron overload, such as hereditary hemochromatosis, treatment typically involves phlebotomy (venesection) to remove excess iron from the body 5, 6, 4.
• For patients with homozygosity of the HFE mutation p.C282Y and hyperferritinemia, venesection can be started without further investigations 4.
• In cases where iron overload is suspected but HFE mutations are absent, magnetic resonance imaging (MRI) may be used to validate iron excess before starting venesection 4.
• Dysmetabolic iron overload syndrome (DIOS) or alcohol-related hemosiderosis can be treated with venesection in selected cases if there is significant deposition of iron in the liver on MRI 4.
• Liver MRI can also be used to monitor the effectiveness of iron chelation therapy and to assess cardiac iron 7.
• In some cases, hyperferritinemia may not require further investigation or treatment, such as when ferritin levels are below 1000 µg/L, transferrin saturation is normal, and liver tests are normal 4.

Diagnostic Approaches

• Serum ferritin and transferrin saturation are the first diagnostic steps to identify the cause of hyperferritinemia 4, 7.
• Liver iron concentration can be assessed by liver biopsy or MRI, with MRI being a non-invasive approach considered the standard method for diagnosing and monitoring hepatic iron overload 7.
• Different technical MRI approaches, such as T2 and T2* relaxometry, can be used to measure liver iron content, and the choice of technique depends on local availability and patient population 7.