Key Facts

Anaemia of chronic disease (ACD), also termed anaemia of inflammation, is the second most common cause of anaemia worldwide. It occurs in the setting of chronic immune activation.

Epidemiology

• Most common cause of anaemia in hospitalised patients
• Prevalence: depends on underlying condition (~30–60% of patients with chronic inflammatory conditions)

Aetiology

• Chronic infections: TB, HIV, osteomyelitis, endocarditis
• Chronic inflammatory disease: RA, SLE, IBD, sarcoidosis
• Malignancy: solid tumours, haematological malignancies
• CKD: reduced EPO production + inflammation

Pathophysiology

• Inflammatory cytokines (IL-6, TNF-α, IL-1) stimulate hepatic hepcidin production
• Hepcidin: master iron regulator — degrades ferroportin on enterocytes and macrophages
  • Blocks intestinal iron absorption
  • Traps iron in macrophages (functional iron deficiency)
• Reduced EPO production and EPO resistance
• Shortened RBC lifespan
• Impaired erythroid progenitor proliferation
• Result: normocytic (or mildly microcytic) anaemia with iron present but sequestered

Symptoms

• Often mild and overshadowed by the underlying disease
• Fatigue, pallor, dyspnoea on exertion
• Usually mild-moderate anaemia (Hb rarely <80 g/L)

Clinical Context

• Patient with known chronic inflammatory/infective/malignant condition
• Anaemia discovered on routine blood tests

Red Flags

• Severe anaemia (Hb <80 g/L) — consider additional cause (iron deficiency, B12/folate, bone marrow infiltration)
• Worsening anaemia in cancer patient (bleeding, bone marrow failure)
• Newly discovered anaemia without obvious cause (investigate for occult malignancy/infection)

Bloods

• FBC: normocytic normochromic anaemia (MCV 75–95 fL); may be mildly microcytic
• Iron studies:
  • Serum iron: LOW
  • Ferritin: NORMAL or RAISED (acute phase reactant)
  • TIBC/transferrin: LOW (key distinguishing feature from IDA)
  • Transferrin saturation: low-normal
• CRP/ESR: elevated (underlying inflammation)
• Reticulocyte count: inappropriately low
• Blood film: normocytic normochromic; no specific features

Special Tests (if diagnostic uncertainty)

• Soluble transferrin receptor (sTfR): raised in true iron deficiency but normal in pure ACD (helps diagnose combined ACD + IDA)
• sTfR/log ferritin ratio: >2 suggests concurrent iron deficiency
• Hepcidin levels: elevated (research/specialist use)
• EPO level: in CKD (low for degree of anaemia)
• Bone marrow: iron stores present (stainable iron in macrophages — Prussian blue); rarely needed

Non-pharmacological

• Treat the underlying cause (most important)
  • Control inflammation (DMARDs for RA, treat infection, cancer treatment)
  • Resolution of underlying cause → anaemia improves

Pharmacological

Mild ACD:

• Often no specific treatment needed; treat underlying cause

Moderate-severe or symptomatic:

• IV iron: if concurrent true iron deficiency (ferritin <100 in inflammatory state; sTfR raised)
  • Ferric carboxymaltose (Ferinject) 1g IV
  • Oral iron poorly absorbed in ACD (hepcidin blocks absorption)

CKD-associated anaemia (NICE NG203):

• Erythropoiesis-stimulating agents (ESAs): epoetin alfa, darbepoetin alfa
  • Target Hb 100–120 g/L (avoid >120 — cardiovascular risk)
  • Ensure iron-replete before starting (transferrin sat >20%, ferritin >200)
• IV iron: first-line in CKD before ESAs (if iron-deficient)

Transfusion:

• Rarely needed; only if symptomatic with very low Hb

Referral Criteria

• Haematology: unexplained anaemia, severe, or diagnostic uncertainty
• Nephrology: CKD-associated anaemia for ESA management

• Prognosis depends on underlying condition
• Anaemia usually mild-moderate and well-tolerated
• Resolves with treatment of underlying cause in many cases
• CKD-anaemia: managed long-term with ESAs and IV iron
• Does not progress to more severe marrow failure

Iron Studies Comparison