From the Guidelines
Elevated ferritin levels should be followed up with a comprehensive workup to determine the underlying cause, including serum iron studies, liver function tests, and genetic testing for hereditary hemochromatosis if transferrin saturation is greater than 45%. The initial step in managing elevated ferritin levels involves identifying the underlying cause, which can range from iron overload conditions to inflammation, liver disease, metabolic syndrome, and certain cancers 1. A comprehensive workup should include:
- Serum iron studies (transferrin saturation, total iron binding capacity)
- Liver function tests
- Hemoglobin A1C
- Genetic testing for hereditary hemochromatosis if transferrin saturation is greater than 45%, specifically looking for HFE gene mutations (C282Y and H63D) 1
Depending on the severity of elevation, a hepatology or hematology consultation may be warranted. For mild to moderate elevations (300-1000 ng/mL) without symptoms, lifestyle modifications including limiting alcohol consumption, maintaining a healthy weight, and reducing dietary iron intake may be beneficial while investigating the cause. However, for significantly elevated levels (>1000 ng/mL), especially with high transferrin saturation, therapeutic phlebotomy may be necessary, typically removing one unit of blood (approximately 500 mL) weekly until ferritin levels normalize, with a target ferritin level of 50-100 lg/L 1. Follow-up ferritin testing should occur every 3-6 months initially, then annually once stabilized. It is essential to note that dietary adjustments are unnecessary during treatment for hemochromatosis, and vitamin C supplements and iron supplements should be avoided 1.
From the FDA Drug Label
For patients with transfusional iron overload, measure serum ferritin monthly to assess for possible overchelation of iron. 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 follow-up for elevated ferritin involves monthly monitoring of serum ferritin levels to assess for possible overchelation of iron.
- If serum ferritin falls below 1000 mcg/L at 2 consecutive visits, consider dose reduction.
- If serum ferritin falls below 500 mcg/L, interrupt therapy with deferasirox tablets and continue monthly monitoring 2.
From the Research
Follow-up for Elevated Ferritin
To approach a case of elevated ferritin, it's crucial to consider the various causes and the appropriate follow-up investigations. The causes of hyperferritinemia can be diverse, including iron overload, inflammation, liver or renal disease, malignancy, and metabolic syndrome 3.
Initial Assessment
- Clinical findings and simple laboratory tests can help identify common causes such as alcoholism, inflammatory syndrome, cytolysis, and metabolic syndrome, which are not typically associated with substantial hepatic iron overload 4.
- Transferrin saturation levels can guide further investigation; if high (>50%), hereditary hemochromatosis should be considered 4.
Further Investigation
- For rarer diseases or when the cause is unclear, additional tests may be necessary to rule out conditions like chronic hematologic diseases or excessive iron intake 4.
- Hepatic MRI can be essential in assessing hepatic iron concentration to rule out overload, especially if there's a high or continuously rising ferritin concentration 4.
- Understanding the role of ferritin in inflammation is also crucial, as hyperferritinemia can be both a biomarker and a mediator of inflammatory conditions 5.