What are the implications and management strategies for a patient with hyperferritinemia (elevated iron levels) and low ferritin?

From the Guidelines

The management of a patient with high iron and low ferritin requires careful evaluation, and the most likely explanation is laboratory error or misinterpretation, as ferritin is normally elevated, not decreased, in iron overload conditions. The first step should be to repeat testing to confirm results, as this combination is unusual and may indicate an error in laboratory testing 1. If confirmed, a comprehensive workup should include transferrin saturation, total iron binding capacity, complete blood count, liver function tests, and possibly genetic testing for hereditary hemochromatosis.

Key Considerations

• The distinction between absolute and functional iron deficiency is crucial, as patients with functional iron deficiency may have normal or elevated serum ferritin levels despite a decrease in transferrin saturation (TSAT) 1.
• TSAT reflects iron that is readily available for erythropoiesis, while serum ferritin reflects storage iron, and both are important in evaluating iron status 1.
• In patients with high iron and low ferritin, it is essential to rule out inflammatory conditions, as these can affect iron metabolism and lead to misleading laboratory results 1.

Treatment Approach

• If hemochromatosis is diagnosed despite the unusual lab values, therapeutic phlebotomy remains the mainstay of treatment, removing 500ml of blood (containing approximately 200-250mg of iron) weekly or biweekly until ferritin normalizes, then maintenance phlebotomies 2-4 times yearly 1.
• Chelation therapy with medications like deferasirox (Exjade, 20-40mg/kg/day) or deferoxamine (Desferal, 20-60mg/kg/day via subcutaneous infusion) may be necessary for patients who cannot tolerate phlebotomy, particularly those with serum ferritin levels > 2500 ng/mL 1.
• Dietary modifications, including limiting alcohol, vitamin C supplements, and iron-rich foods, should also be considered as part of the treatment plan.

Monitoring and Follow-up

• Regular monitoring of iron studies, liver function, and cardiac status is essential, as untreated iron overload can lead to cirrhosis, diabetes, cardiomyopathy, and arthropathy 1.
• The goal of treatment should be to decrease ferritin levels to < 100 ng/mL and maintain a TSAT < 50%, while also preventing complications associated with iron overload 1.

From the FDA Drug Label

The evidence should include the transfusion of at least 100 mL/kg of packed red blood cells (e.g., at least 20 units of packed red blood cells for a 40 kg person or more in individuals weighing more than 40 kg), and a serum ferritin consistently greater than 1000 mcg/L Monitor serum ferritin monthly and adjust the dose of deferasirox tablets, if necessary, every 3 to 6 months based on serum ferritin trends Use the minimum effective dose to achieve a trend of decreasing ferritin Adjust dose based on serum ferritin levels o 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 o If the serum ferritin falls below 500 mcg/L, interrupt deferasirox tablets therapy and continue monthly monitoring

The implications of high iron and low ferritin are not directly addressed in the provided drug label. However, it can be inferred that low ferritin levels may require dose reduction or interruption of deferasirox therapy.

• Key points:
  • Monitor serum ferritin levels monthly
  • Adjust dose based on serum ferritin trends
  • Use the minimum effective dose to achieve a trend of decreasing ferritin
  • Consider dose reduction if serum ferritin falls below 1000 mcg/L
  • Interrupt therapy if serum ferritin falls below 500 mcg/L 2

From the Research

Implications of High Iron and Low Ferritin

• High iron levels and low ferritin can be indicative of hyperferritinemia, a condition where the body has an excess of iron [(3,4)].
• This condition can lead to various complications, including liver damage, heart problems, and diabetes 4.
• Low ferritin levels, on the other hand, can indicate iron deficiency, which can cause anemia, fatigue, and other health issues [(5,6)].

Management Strategies

• Therapeutic phlebotomy is a common treatment for hyperferritinemia, where blood is removed from the body to reduce iron levels 4.
• Iron chelation therapy, such as deferasirox, can also be used to reduce iron levels, especially in patients who cannot undergo phlebotomy [(3,7)].
• Dietary management, including avoiding iron supplements and excess vitamin C, can also help reduce iron levels 4.
• In patients with iron deficiency, iron supplementation may be necessary to treat anemia and other symptoms 6.

Diagnostic Considerations

• Serum ferritin levels are not always a reliable indicator of iron status, especially in patients with inflammatory conditions 5.
• Transferrin saturation (TSAT) and other markers of iron availability should also be assessed to diagnose iron deficiency 5.
• Regular monitoring of serum ferritin and TSAT levels is recommended in patients at risk of iron deficiency or overload [(5,6)].