What is the interpretation of elevated ferritin levels with concurrent hypoferritinemia (low iron levels) in a blood test?

From the Guidelines

High ferritin levels with low iron levels typically suggest iron sequestration, which commonly occurs in a condition called anemia of chronic inflammation (also known as anemia of chronic disease). This pattern indicates that your body has adequate iron stores but is unable to properly utilize this iron for red blood cell production. You should consult with your healthcare provider for proper diagnosis and treatment, as this pattern can be seen in several conditions including chronic infections, autoimmune disorders, liver disease, or certain types of cancer 1. Your doctor may recommend additional tests such as transferrin saturation, total iron binding capacity (TIBC), or a complete blood count to determine the underlying cause. Some key points to consider when interpreting ferritin and iron levels include:

• Ferritin levels can be influenced by inflammatory states, and should be interpreted in the context of patient-specific conditions, such as chronic kidney disease and underlying inflammatory states 1.
• The distinction between absolute and functional iron deficiency is crucial to understanding what constitutes adequate TSAT and serum ferritin levels in patients 1.
• Treatment will depend on the specific diagnosis but may include addressing the underlying condition rather than iron supplementation, as adding more iron might not help and could potentially be harmful. This pattern occurs because inflammatory cytokines trigger increased production of hepcidin, a hormone that blocks iron release from storage sites, resulting in functional iron deficiency despite adequate or even excessive iron stores in the body. It is essential to monitor the TSAT and serum ferritin at least once every 3 months, and erythropoiesis can be optimized by adjusting the pro-rated weekly dose of IV iron to maintain adequate iron status 1.

From the Research

Interpretation of High Ferritin and Low Iron Levels

• High ferritin levels can indicate an acute phase reaction, which is often seen in inflammatory conditions, rather than just iron overload 2, 3.
• Low iron levels, despite high ferritin, can be due to the body's inflammatory response, where iron is diverted into ferritin stores, making it unavailable for other uses 4.
• This combination of high ferritin and low iron can be seen in various conditions, including infections, cardiovascular diseases, endocrinological disorders, autoimmune diseases, and malignancies 2.

Possible Causes

• Inflammatory bowel disease (IBD) can lead to iron deficiency anemia, and high ferritin levels may indicate an inflammatory response rather than iron overload 5.
• Hyperferritinemia can be caused by a range of conditions, including adult-onset Still's disease, hemophagocytic lymphohistiocytosis, and diffuse large B-cell lymphoma 2.
• The presence of high ferritin levels requires thorough investigation to differentiate between potential underlying conditions and to guide management 2, 3, 6.

Diagnostic Approach

• A diagnostic workup for hyperferritinemia should include a thorough medical history, physical examination, and laboratory tests to rule out underlying conditions 3.
• The measurement of C-reactive protein (CRP) levels can help predict responsiveness to iron therapy in patients with inflammatory bowel disease and iron deficiency anemia 5.
• An algorithm for the diagnostic workup and management of hyperferritinemia should be followed to ensure appropriate treatment and reduce morbidity and mortality 3.