What causes elevated ferritin levels and anemia?

From the Guidelines

Elevated ferritin levels alongside anemia are most likely caused by anemia of chronic disease, where inflammation blocks iron utilization despite adequate stores, as seen in chronic inflammatory conditions such as rheumatoid arthritis, inflammatory bowel disease, and chronic infections 1.

Causes of Elevated Ferritin and Anemia

The combination of elevated ferritin levels and anemia can be attributed to various conditions, including:

• Iron-loading anemias like thalassemia and sideroblastic anemia, where the body produces abnormal red blood cells while accumulating excess iron
• Chronic inflammatory conditions, such as rheumatoid arthritis, inflammatory bowel disease, and chronic infections, which cause anemia of chronic disease
• Liver disease, particularly alcoholic liver disease and non-alcoholic fatty liver disease, which can elevate ferritin while causing anemia through various mechanisms
• Hemochromatosis with concurrent vitamin deficiencies, certain cancers, and renal failure, which can also present with this combination

Diagnosis and Treatment

Diagnosis typically requires comprehensive blood tests, including complete blood count, iron studies, and potentially genetic testing or bone marrow examination 1. Treatment must address the underlying cause rather than simply supplementing iron, which could worsen iron overload in many of these conditions. In patients with inflammation, the lower limit of serum ferritin consistent with normal iron stores should be increased to 100 μg/L, and hypoferraemia should be considered likely if transferrin saturation (TfS) is below 16% and serum ferritin is between 30 and 100 g/L 1.

Key Considerations

• In the presence of biochemical evidence of inflammation, the diagnostic criteria for anemia of chronic disease (ACD) are a serum ferritin > 100 mcg/L and transferrin saturation < 16% 1
• If the serum ferritin level is between 30 mcg/L and < 100 mcg/L, a combination of true iron deficiency and ACD is likely 1
• Determination of the causal factors is crucial for effective treatment, as simply supplementing iron could worsen iron overload in many of these conditions 1

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Causes of Elevated Ferritin Levels and Anemia

• Elevated ferritin levels can be caused by various conditions, including:
  • Inflammatory conditions such as adult-onset Still's disease, systemic juvenile idiopathic arthritis, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome 2
  • Malignancy, with 153 out of 627 patients in one study having elevated ferritin levels due to cancer 2
  • Iron-overload syndromes, which were the second most common cause of elevated ferritin levels in the same study 2
  • Chronic liver disease, which can cause hyperferritinemia due to disruption of iron metabolism 3
  • Infections, which can cause elevated ferritin levels as an acute-phase reactant 4
• Anemia can also be a cause of elevated ferritin levels, particularly anemia of chronic inflammation 2
• Other conditions that can cause elevated ferritin levels include:
  • Hematologic disorders such as thalassemia syndromes, myelodysplastic syndrome, myelofibrosis, sideroblastic anemias, sickle cell disease, or pyruvate kinase deficiency 5
  • Rheumatic conditions such as adult-onset Still's disease or hemophagocytic lymphohistiocytosis 5
  • Kidney failure, which can cause hyperferritinemia due to decreased iron excretion 5

Diagnostic Considerations

• Elevated ferritin levels should be investigated further to determine the underlying cause, as they can be a marker for severe underlying conditions 6
• A thorough diagnostic workup is essential to differentiate between potential underlying conditions and to reduce morbidity and mortality 6
• Ferritin levels should not be overlooked as merely an indicator of iron status or inflammation, but rather as a potential marker for underlying severe conditions 6
• Transferrin saturation and other laboratory tests can help differentiate between iron overload disorders and other causes of hyperferritinemia 5, 3