Diagnosis of Anemia of Chronic Disease (ACD)

Introduction to ACD

• The pattern of low serum iron, low transferrin saturation, low TIBC, and normal ferritin is characteristic of anemia of chronic disease (ACD), also known as anemia of inflammation, according to the European Crohn’s and Colitis Organisation 1, 2

Interpretation of Laboratory Pattern

• A low serum iron level combined with low TIBC distinguishes ACD from pure iron deficiency, where TIBC would be elevated, as stated by the American Gastroenterological Association 1, 2
• Low transferrin saturation (<16-20%) reflects poor iron availability for erythropoiesis despite adequate stores, as indicated by the National Institute of Diabetes and Digestive and Kidney Diseases 1, 2
• Normal ferritin indicates that body iron stores are preserved, ruling out absolute iron deficiency, according to the European Crohn’s and Colitis Organisation 1, 2

Critical Clinical Context

• The presence of underlying inflammation or chronic disease should be immediately evaluated using inflammatory markers such as elevated PCR, VSG, and leucocytosis, as recommended by the American College of Gastroenterology 1, 2
• Associated conditions such as inflammatory bowel disease, chronic infections, neoplasias, and autoimmune diseases should be considered, as stated by the Crohn’s and Colitis Foundation 1, 2

Important Diagnostic Considerations

• In the context of inflammation, ferritin interpretation changes dramatically: without inflammation, ferritin <30 μg/L defines iron deficiency, while with inflammation, ferritin up to 100 μg/L may be compatible with iron deficiency, according to the National Institute of Diabetes and Digestive and Kidney Diseases 1, 3
• Ferritin >100 μg/L + transferrin saturation <16-20% is a diagnostic criterion for ACD, as indicated by the European Crohn’s and Colitis Organisation 1, 2, 3

Mixed Anemia Scenario

• If ferritin is between 30-100 μg/L, strongly consider a combination of true iron deficiency and ACD, as recommended by the American College of Gastroenterology 1, 2, 3
• In this case, the soluble transferrin receptor (sTfR) may help: elevated in iron deficiency, normal or low in pure ACD, according to the National Institute of Diabetes and Digestive and Kidney Diseases 1, 2

Next Diagnostic Steps

• Confirm inflammation by requesting PCR and VSG, as recommended by the American College of Gastroenterology 1, 2
• Identify the underlying disease through a targeted clinical history of chronic infections, neoplasias, autoimmune diseases, and inflammatory bowel disease, as stated by the Crohn’s and Colitis Foundation 1

Therapeutic Implications

• Primary treatment should target the underlying disease, according to the European Crohn’s and Colitis Organisation 1, 4, 5
• Correction of anemia with recombinant erythropoietin may be effective in ACD when treatment of the underlying disease is insufficient, but this requires higher doses than in other forms of anemia, as indicated by the National Institute of Diabetes and Digestive and Kidney Diseases 1, 4, 5

Interpretation of Ferritin Levels in Acute Ulcerative Colitis

Understanding Ferritin Interpretation in Inflammatory States

• A ferritin level of 55 μg/L in a patient with acute ulcerative colitis indicates iron deficiency, as this value falls within the diagnostic range for iron deficiency in the presence of inflammation (ferritin up to 100 μg/L may still be consistent with iron deficiency) 6, 7
• The critical principle is that ferritin interpretation depends entirely on the presence or absence of inflammation, with ferritin up to 100 μg/L potentially indicating iron deficiency in inflammatory states 6, 7
• With inflammation, as in acute ulcerative colitis, ferritin levels between 30-100 μg/L may indicate a combination of true iron deficiency and anemia of chronic disease 6, 7

Diagnostic Testing

• To confirm the diagnosis, additional tests such as transferrin saturation (TSAT), C-reactive protein (CRP), complete blood count with MCV and RDW, and soluble transferrin receptor (sTfR) should be obtained 6, 7
• TSAT <16-20% supports iron deficiency even with inflammation present 6, 7
• CRP confirms active inflammation and guides ferritin interpretation 6, 7
• sTfR is the most reliable test in inflammatory states, elevated in iron deficiency and normal/low in pure anemia of chronic disease 6, 7

Treatment Implications

• Iron supplementation is recommended in all ulcerative colitis patients when iron deficiency anemia is present 6, 7
• The primary therapeutic approach should include treating the underlying UC inflammation first and providing iron supplementation once iron deficiency is confirmed 6, 7

Ferritin Interpretation and Management in Ulcerative Colitis

1. Pathophysiological Meaning of a High Ferritin Level

• Ferritin of 622 µg/L in a patient with ulcerative colitis reflects anemia of chronic disease driven by active intestinal inflammation rather than iron overload. 8
• Ferritin functions as an acute‑phase reactant; its elevation during inflammation makes interpretation fundamentally different in ulcerative colitis compared with healthy individuals. 8

2. Diagnostic Thresholds Recommended by the European Crohn’s and Colitis Organisation (ECCO)

*These thresholds are derived from ECCO guidance and apply to patients with inflammatory bowel disease. 8

3. Required Additional Laboratory Assessment

• Ferritin alone cannot determine true iron status; measurement of transferrin saturation (TSAT) is essential. A TSAT < 20 % confirms ACD, while TSAT < 16 % suggests co‑existing iron deficiency. 8
• C‑reactive protein (CRP) should be measured to quantify the inflammatory burden. 9
• A complete blood count with mean corpuscular volume (MCV) and red‑cell distribution width (RDW) helps characterize the type of anemia. 8

4. Therapeutic Priorities

• The primary target is control of ulcerative colitis inflammation, which is the root cause of the elevated ferritin and any associated anemia. 9
• Optimizing IBD therapy to achieve clinical remission should precede any iron‑related interventions. 9
• Iron supplementation should not be started based solely on a high ferritin level. 8

Iron Supplementation Decision Algorithm

5. Monitoring and Follow‑Up

• Ferritin concentrations are expected to decline as ulcerative colitis inflammation is brought under control; persistent elevation suggests inadequate disease control or an alternative pathology. 8
• Re‑measure ferritin, CRP, and hemoglobin 4–8 weeks after intensifying ulcerative colitis therapy. 9
• Ongoing high ferritin after appropriate IBD management warrants investigation for other inflammatory conditions or complications. 8