At what serum ferritin level is iron deficiency typically considered?

Serum Ferritin Levels for Diagnosing Iron Deficiency

Iron deficiency is typically considered at a serum ferritin level <30 μg/L in patients without inflammation, while in patients with inflammation, serum ferritin up to 100 μg/L may still be consistent with iron deficiency. 1

Diagnostic Thresholds Based on Inflammatory Status

Without Inflammation

• Serum ferritin <30 μg/L is the appropriate diagnostic criterion for iron deficiency in patients without clinical, endoscopic, or biochemical evidence of active inflammation 1
• Some evidence suggests that a cut-off of <15 μg/L is highly specific (specificity 0.99) for absolute iron deficiency 1
• A serum ferritin threshold of <45 μg/L may provide optimal trade-off between sensitivity and specificity for iron deficiency in clinical practice 1
• Recent research suggests that ferritin levels ≤50 ng/mL may be indicative of early iron deficiency based on correlation with soluble transferrin receptor to hepcidin ratio 2

With Inflammation

• In patients with inflammation (elevated CRP, clinical inflammation), serum ferritin up to 100 μg/L may still be consistent with iron deficiency 1
• If serum ferritin is between 30-100 μg/L in the presence of inflammation, a combination of true iron deficiency and anemia of chronic disease is likely 1
• Serum ferritin >100 μg/L with transferrin saturation <20% in the presence of inflammation is diagnostic of anemia of chronic disease 1

Additional Diagnostic Parameters

• Transferrin saturation (TSAT) <20% should be considered alongside ferritin for accurate diagnosis of iron deficiency, especially in inflammatory conditions 1, 3
• In inflammatory conditions, if serum ferritin is 100-300 μg/L, TSAT <20% is required to confirm iron deficiency 3
• Other markers suggestive of iron deficiency include low mean corpuscular volume (MCV), raised red cell distribution width (RDW), microcytic hypochromic red cells on blood film, low serum iron, and raised total iron-binding capacity 1

Special Populations

Inflammatory Bowel Disease

• In IBD patients, the diagnostic criteria for iron deficiency depend on the level of inflammation, with serum ferritin <30 μg/L in remission and up to 100 μg/L in active disease 1
• Regular monitoring is recommended: every 6-12 months in remission or mild disease, and at least every 3 months in patients with active disease 1

Chronic Kidney Disease

• In CKD patients, absolute iron deficiency has been defined as serum ferritin <100 ng/mL and TSAT <20% 1
• Functional iron deficiency can occur despite normal or elevated serum ferritin levels, particularly in patients receiving erythropoiesis-stimulating agents 1

Chronic Heart Failure

• Recent evidence suggests that TSAT <20% (as long as serum ferritin is <400 μg/L) may be more reliable than serum ferritin alone for diagnosing iron deficiency in heart failure patients 4

Clinical Pitfalls

• Serum ferritin is an acute phase reactant that increases during inflammation, which can mask iron deficiency 1, 3
• Inflammatory cytokines trigger increased hepcidin, which restricts dietary iron uptake and promotes iron sequestration, leading to functional iron deficiency despite normal or high ferritin levels 3
• In patients with chronic inflammatory conditions (IBD, CKD, heart failure), standard thresholds for iron deficiency do not apply, and TSAT should always be assessed alongside ferritin 3
• Relying solely on ferritin without considering inflammatory status may lead to underdiagnosis of iron deficiency in patients with chronic inflammation 3, 4

By understanding these context-dependent thresholds for serum ferritin, clinicians can more accurately diagnose iron deficiency and initiate appropriate treatment to improve patient outcomes and quality of life.