Anaemia of chronic disease

Definition. Also called anaemia of inflammation — a mild to moderate, usually normocytic normochromic anaemia occurring in chronic infection, inflammation or malignancy. It is the second commonest anaemia worldwide and the commonest anaemia in hospitalised older patients.

Causes. Chronic infections (tuberculosis, osteomyelitis, endocarditis, HIV), chronic inflammatory disease (rheumatoid arthritis, polymyalgia rheumatica, giant cell arteritis, inflammatory bowel disease), malignancy, chronic kidney disease, heart failure, COPD and diabetes.

Pathogenesis — three mechanisms. Inflammatory cytokines (IL-6, TNF-α, IL-1, interferon-γ) drive: (a) IL-6-induced hepcidin release from the liver, which degrades ferroportin and traps iron in macrophages and enterocytes — producing functional iron deficiency; (b) blunted erythropoietin production and reduced marrow responsiveness to EPO; and (c) shortened red cell survival. Hepcidin is the central molecule.

Laboratory features. Hb usually 8–11 g/dL, normocytic (microcytic in 25–30% if long-standing), low reticulocyte count, low serum iron with low TIBC/transferrin, transferrin saturation low or normal, normal or high ferritin (an acute-phase reactant), raised CRP and ESR, and normal soluble transferrin receptor.

Distinction from iron deficiency (very high yield). Parameter Iron deficiency Anaemia of chronic disease Serum ferritin Low (<30 ng/mL) Normal or high TIBC / transferrin High Low Transferrin saturation <16% Low or normal Soluble transferrin receptor High Normal sTfR / log ferritin index >2 <1 Serum hepcidin Low High The two frequently coexist in the elderly — use the sTfR/log ferritin index, or a ferritin cut-off of 100 ng/mL in the presence of inflammation.

Management. Treat the underlying disease — this is the definitive therapy and the anaemia resolves with disease control. Do not give oral iron unless true deficiency coexists, because high hepcidin blocks its absorption; if iron is needed, use intravenous iron, which bypasses the hepcidin-ferroportin block. Erythropoiesis-stimulating agents are indicated in CKD and chemotherapy-induced anaemia, targeting Hb 10– 11.5 g/dL (never normalisation, because of thrombosis, hypertension and tumour progression risk), with iron repletion first. Transfuse only for symptomatic anaemia.

Hepcidin-targeted and HIF-PHI therapy. Hypoxia-inducible factor prolyl-hydroxylase inhibitors (roxadustat, daprodustat, vadadustat) are now approved for anaemia of CKD; they are orally active, raise endogenous erythropoietin and simultaneously suppress hepcidin, thereby improving iron mobilisation — a mechanistic advantage over conventional ESAs in inflammatory states, although cardiovascular safety signals mean current guidance restricts them to selected patients. Anti-hepcidin and anti-IL-6 agents are in trials for anaemia of inflammation.