Anaemia of Chronic Disease

Also called anaemia of inflammation.

It is a multifactorial anaemia that occurs as part of a chronic inflammatory disorder — most often chronic infection, an autoimmune disease (especially rheumatoid arthritis), kidney disease, heart failure, or cancer.

The same process can begin acutely during almost any infection or inflammation, including trauma, critical illness, and the post-operative period.

Worldwide it is the second most common anaemia, and it is the most common cause of normocytic anaemia in hospitalised patients.

Red cells are normocytic early on; with time they may become microcytic. The anaemia is usually mild — haemoglobin is generally above 80 g/L unless another mechanism also contributes.

Pathophysiology

Three mechanisms operate together:

• Slightly shortened RBC survival, thought to be from increased haemophagocytosis by macrophages in inflammatory disease, mostly in the acute setting.
• Impaired erythropoiesis from decreased erythropoietin (EPO) production and reduced marrow responsiveness to EPO. EPO levels are usually above the reference range but remain inappropriately low for the degree of anaemia, because inflammatory cytokines suppress EPO gene expression. Cytokines (IL-1β, IL-6, TNF-α, interferon-γ) also directly impair erythroid proliferation and differentiation.
• Altered iron metabolism driven by hepcidin. IL-6 upregulates hepatic hepcidin via JAK-STAT3 signalling; hepcidin degrades ferroportin — the only cellular iron exporter — on enterocytes, macrophages and hepatocytes, reducing intestinal iron absorption and trapping iron in the reticuloendothelial system. The result is a functional iron deficiency despite adequate or increased total-body iron stores.

Diagnosis

Suspect it in a patient with microcytic or normocytic anaemia who also has a chronic illness, infection, inflammation or cancer. The clinical picture is usually that of the underlying disorder.

Order a full blood count with reticulocyte count and iron studies (serum iron, ferritin, transferrin or total iron-binding capacity). The characteristic pattern is a low serum iron with a low or low-normal transferrin and a normal or elevated ferritin — in contrast to true iron deficiency, where transferrin/TIBC is high and ferritin is low. The reticulocyte count is low.

Iron deficiency can be superimposed on anaemia of chronic disease, and it is easily missed because serum ferritin is raised as an acute-phase reactant. In a patient with inflammation, a ferritin below about 100 ng/mL (below 200 ng/mL in chronic kidney disease), particularly with transferrin saturation under 20%, suggests coexisting true iron deficiency. A low serum iron alone must not be read as iron deficiency: serum iron and transferrin both fall rapidly as part of the acute-phase response regardless of iron stores, so iron and transferrin should always be interpreted together.

When standard iron studies are equivocal, the soluble transferrin receptor (sTfR, elevated in iron deficiency but normal in anaemia of chronic disease), the sTfR–ferritin index, and reticulocyte haemoglobin content (low in functional iron deficiency) can help; each can still be confounded by inflammation. ESR and CRP are non-specific markers that support the presence of an inflammatory process.

Management

• Treat the underlying disorder — this is the mainstay, and the anaemia usually improves as the inflammation is controlled. Because the anaemia is mild, transfusion is rarely needed.
• Iron where concomitant iron deficiency is present or strongly suspected. Oral iron is often ineffective because hepcidin blocks intestinal absorption, so intravenous iron is preferred in this setting. Iron is generally avoided when there is no suspected iron deficiency and in acute uncontrolled infection. See Anaemia for current AJGP guidance on IV ferric carboxymaltose infusions.
• Erythropoiesis-stimulating agents (epoetin alfa, darbepoetin alfa) in selected patients — chronic kidney disease, some chemotherapy-induced anaemia, and occasionally before elective surgery — with attention to thromboembolic risk and target haemoglobin. KDIGO 2026 recommends ESAs as first-line pharmacotherapy for CKD-associated anaemia once correctable causes are addressed.