Anaemia of Chronic Disease (ACD) and Inflammation

PATHCHAT Edition No. 39
Please contact your local Ampath pathologist for more information.

Author: Dr. Ingrid Aronson, BSc(Hons), MBChB, MMed(Path)(Haem)

Introduction

🔹 What is Anaemia of Chronic Disease (ACD)?

• ACD is the leading cause of anaemia in hospitalized patients and the second-most common cause of anaemia after iron deficiency.
• It occurs in chronic infections, autoimmune diseases, and malignancies.
• The severity of anaemia correlates with the severity of the underlying disease.

✅ Key Mechanisms Behind ACD:

1. Disordered iron metabolism due to increased hepcidin production.
2. Suppression of erythropoiesis (red blood cell production).
3. Shortened red blood cell survival.

📌 Hepcidin, a liver-produced hormone, is the central regulator of iron metabolism and plays a crucial role in ACD.

Iron Metabolism & the Role of Hepcidin

🔹 Key Functions of Iron in the Body:

• Iron is essential for haemoglobin synthesis and oxygen transport.
• The body requires >20 mg of iron per day, most of which is recycled from aged red blood cells.
• Storage sites include hepatocytes and macrophages.

✅ Iron Balance is Regulated by Hepcidin:

• Hepcidin binds to ferroportin (the iron export protein) on hepatocytes, macrophages, and enterocytes.
• This causes ferroportin degradation, preventing iron release into the plasma.
• Iron then becomes trapped in cells, leading to hypoferremia (low serum iron) despite adequate iron stores.

📌 Increased hepcidin in ACD prevents iron from being available for red blood cell production, causing functional iron deficiency.

Key Features of ACD

✅ Laboratory Findings in ACD:

• Low serum iron.
• Low transferrin levels (due to downregulation of transferrin synthesis).
• High ferritin levels (iron is trapped in macrophages and hepatocytes).
• Normal soluble transferrin receptor (sTfr) levels (unlike iron deficiency, where sTfr is elevated).

✅ Characteristics of ACD Anaemia:

• Usually normocytic and normochromic.
• Hypochromic and microcytic in <25% of cases.
• Mild to moderate anaemia (severity depends on the underlying chronic condition).

📌 ACD is often difficult to distinguish from iron deficiency, especially when both conditions coexist.

Distinguishing ACD from Iron Deficiency Anaemia (IDA)

✅ Key Laboratory Differences Between ACD and IDA:

✔ Anaemia of Chronic Disease (ACD):

• Serum Iron: Low.
• Transferrin: Low.
• Transferrin Saturation: Low.
• Ferritin: High.
• Soluble Transferrin Receptor (sTfr): Normal.

✔ Iron Deficiency Anaemia (IDA):

• Serum Iron: Low.
• Transferrin: High (compensatory increase).
• Transferrin Saturation: Low.
• Ferritin: Low.
• Soluble Transferrin Receptor (sTfr): High.

📌 sTfr can help differentiate ACD from IDA, as it is normal in ACD but elevated in iron deficiency.

Treatment of ACD

✅ Management Strategies for ACD:

1. Treat the underlying disease (infection, inflammation, malignancy).
2. Red blood cell transfusions (for Hb < 8 g/dL).
3. Iron supplementation (preferably intravenous in selected cases).
4. Erythropoiesis-stimulating agents (ESA) to boost red cell production (target Hb <13 g/dL).
5. Novel therapies targeting hepcidin regulation are under development.

📌 Oral iron supplementation is often ineffective in ACD due to iron sequestration by hepcidin.

Key Takeaways for Clinicians

✅ ACD is the most common anaemia in hospitalized patients and is associated with chronic inflammation.
✅ Hepcidin plays a central role in iron sequestration, leading to functional iron deficiency.
✅ ACD is normocytic and normochromic in most cases, but it can be microcytic in 25% of patients.
✅ A combination of iron studies, ferritin levels, and soluble transferrin receptor testing helps differentiate ACD from iron deficiency.
✅ Treatment focuses on managing the underlying disease and, in select cases, iron therapy or erythropoiesis-stimulating agents.

📌 Emerging therapies targeting hepcidin could offer new treatment options for ACD in the future.