What is the appropriate workup for a patient with elevated ferritin (iron storage protein) levels?

From the Guidelines

The workup for elevated ferritin should begin with a thorough history and physical examination, followed by targeted laboratory testing to determine the underlying cause, as recommended by the American Association for the Study of Liver Diseases 1. The initial tests should include:

• Complete blood count
• Liver function tests
• Iron studies (serum iron, total iron binding capacity, transferrin saturation)
• Hemoglobin A1C
• Renal function tests If transferrin saturation is greater than 45%, genetic testing for hereditary hemochromatosis (HFE gene mutations) should be performed 1. For patients with normal transferrin saturation, evaluation should focus on other common causes such as:
• Inflammation
• Liver disease
• Metabolic syndrome
• Alcohol consumption Additional testing may include:
• Hepatitis serology
• Alcohol use assessment
• Evaluation for metabolic syndrome components If ferritin is markedly elevated (>1000 ng/mL) without obvious cause, consider rare conditions like hemophagocytic lymphohistiocytosis or Still's disease 1. Imaging studies such as liver ultrasound or MRI may be indicated to assess for iron overload or liver damage 1. The workup should be tailored to the patient's clinical presentation, as ferritin is an acute phase reactant that can be elevated in many inflammatory conditions, and the degree of elevation often correlates with the severity of the underlying disorder 1.

From the FDA Drug Label

Deferasirox tablets therapy should only be considered when a patient has evidence of chronic transfusional iron overload. 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 Prior to starting therapy, or increasing dose, evaluate: Serum ferritin level Baseline renal function: Obtain serum creatinine in duplicate (due to variations in measurements) Calculate the estimated glomerular filtration rate (eGFR). Obtain urinalyses and serum electrolytes to evaluate renal tubular function Serum transaminases and bilirubin Baseline auditory and ophthalmic examinations

The appropriate workup for a patient with elevated ferritin levels includes:

• Evaluating serum ferritin level
• Assessing baseline renal function by:
  • Obtaining serum creatinine in duplicate
  • Calculating the estimated glomerular filtration rate (eGFR)
  • Obtaining urinalyses and serum electrolytes to evaluate renal tubular function
• Checking serum transaminases and bilirubin levels
• Conducting baseline auditory and ophthalmic examinations 2

From the Research

Appropriate Workup for Elevated Ferritin Levels

The workup for a patient with elevated ferritin levels involves a comprehensive approach to determine the underlying cause. Key steps include:

• Obtaining a detailed patient history to identify potential causes such as alcohol consumption, metabolic syndrome, obesity, diabetes, liver disease, malignancy, infection, or inflammation 3
• Ordering laboratory tests, including transferrin saturation, serum concentrations of alanine and aspartate aminotransferases (ALT, AST), and testing for HFE mutations 4, 5
• Performing liver imaging and, if necessary, liver biopsy to assess liver iron concentration 4, 5
• Evaluating for non-alcoholic fatty liver disease, which is frequently detected in patients with iron metabolism disorders 5

Interpretation of Laboratory Results

When interpreting laboratory results, it is essential to consider the following:

• Elevated serum ferritin concentrations can be caused by a wide range of conditions, including iron-overload syndromes, malignancy, infection, and inflammatory diseases 6
• The presence of HFE mutations does not necessarily indicate hereditary hemochromatosis, as these mutations can be present in individuals without iron overload 7
• The probability of being a C282Y homozygote increases as the ferritin level increases, but iron loading HFE mutations are unlikely to be the most common cause of an elevated serum ferritin level in patients with mild hyperferritinemia 7

Referral and Treatment

Referral to a specialist, such as a gastroenterologist, hematologist, or physician with an interest in iron overload, is appropriate if:

• Serum ferritin is >1000 µg/L 3
• The cause of elevated serum ferritin is still unclear after initial evaluation 3
• Phlebotomy may be useful in the treatment of patients with iron metabolism disorders, particularly those with non-alcoholic fatty liver disease 5