What causes elevated ferritin levels?

From the Guidelines

Elevated ferritin levels can be caused by several conditions, including iron overload disorders, inflammation, liver damage, certain cancers, frequent blood transfusions, metabolic conditions, and rare genetic disorders. According to the most recent and highest quality study 1, in patients presenting with increased serum ferritin concentrations, it is mandatory to search for common causes of hyperferritinemia before genetic tests are carried out. Some of the common causes of elevated ferritin levels include:

• Chronic alcohol consumption
• Inflammation (check for CRP)
• Cell necrosis (check for AST, ALT and CK)
• Tumors (ESR, CT scan)
• Non-alcoholic fatty liver disease (NAFLD) and/or the metabolic syndrome (check for blood pressure, BMI, cholesterol, triglycerides, and serum glucose) Other conditions that can cause elevated ferritin levels include:
• Hereditary hemochromatosis
• Rheumatoid arthritis, lupus, or inflammatory bowel disease
• Alcoholic liver disease, hepatitis, or nonalcoholic fatty liver disease
• Leukemia, lymphoma, and breast cancer
• Frequent blood transfusions
• Obesity, insulin resistance, and metabolic syndrome
• Gaucher disease and porphyria
• Excessive alcohol consumption and certain medications It is essential to determine the underlying cause of elevated ferritin levels before starting any treatment, and additional tests like transferrin saturation or genetic testing may be recommended 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

Elevated ferritin levels can be caused by chronic transfusional iron overload, which occurs when a patient receives multiple blood transfusions, leading to an accumulation of iron in the body. This condition is characterized by serum ferritin levels consistently greater than 1000 mcg/L 2.

Key points to consider:

• Transfusional iron overload: a condition where iron accumulates in the body due to multiple blood transfusions
• Serum ferritin levels: a measure of iron stores in the body, with elevated levels indicating iron overload
• Threshold for elevated ferritin: consistently greater than 1000 mcg/L 2

From the Research

Causes of Elevated Ferritin

Elevated ferritin levels can be caused by a variety of conditions, including:

• Inflammatory conditions such as adult-onset Still's disease, systemic juvenile idiopathic arthritis, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome 3
• Malignancy, which was the most frequent condition associated with elevated ferritin levels in one study 3
• Iron-overload syndromes, such as hereditary hemochromatosis 3, 4
• Infections, including severe infections and sepsis 5, 6
• Chronic liver disease, which can lead to hyperferritinemia due to inflammation and iron overload 4, 6
• Kidney failure, which can cause hyperferritinemia due to decreased iron excretion and inflammation 4
• Rheumatic conditions, such as rheumatoid arthritis and lupus 4
• Hematological disorders, such as thalassemia, myelodysplastic syndrome, and sickle cell disease 4

Conditions Associated with Extremely Elevated Ferritin

Extremely elevated ferritin levels (above 6000 μg/L) are often associated with:

• Hemophagocytic lymphohistiocytosis (HLH), a rare and life-threatening condition characterized by excessive immune activation and tissue damage 5
• Severe infections, such as sepsis and meningitis 5
• Malignancy, particularly hematological malignancies such as leukemia and lymphoma 5, 6
• Chronic liver disease, particularly cirrhosis and liver failure 6

Diagnostic Approach

The diagnostic approach to elevated ferritin levels involves:

• Evaluating the patient's medical history and physical examination to identify potential causes of hyperferritinemia 3, 4
• Ordering laboratory tests, such as complete blood count, liver function tests, and iron studies, to evaluate for underlying conditions 4
• Considering genetic testing for hereditary hemochromatosis and other iron-overload disorders 4
• Using imaging studies, such as MRI, to evaluate for iron overload and tissue damage 4