About This Page
This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
Key points
- Normocytic normochromic anaemia (occasionally mildly microcytic) in the setting of chronic inflammation, infection, malignancy, or autoimmune disease
- Iron studies pattern: LOW serum iron, LOW TIBC (both low — key difference from iron deficiency where TIBC is raised), NORMAL or RAISED ferritin
- Pathophysiology: hepcidin (acute phase protein) blocks iron release from macrophages and absorption from gut → functional iron deficiency despite adequate stores
- Do NOT treat with iron supplementation (iron stores are adequate — the problem is iron sequestration)
- Treatment: manage the underlying condition. Erythropoiesis-stimulating agents (ESAs) for anaemia of CKD
Overview
Anaemia of chronic disease (ACD), also called anaemia of inflammation, is the second most common anaemia worldwide after iron deficiency. It occurs in the context of chronic inflammatory conditions (rheumatoid arthritis, IBD), chronic infections (TB, osteomyelitis), and malignancy. The key mediator is hepcidin — a hepatic peptide hormone upregulated by IL-6 during inflammation. Hepcidin blocks ferroportin (the iron export channel on macrophages and enterocytes), trapping iron inside cells and reducing circulating iron availability for erythropoiesis. This is an adaptive response designed to withhold iron from pathogens.
Epidemiology
ACD is extremely common in hospitalised patients — present in up to 40% of inpatients with chronic disease. It is the most common anaemia in hospitalised patients. Any chronic inflammatory condition can cause it, including rheumatoid arthritis, SLE, IBD, chronic infections, heart failure, and malignancy. It frequently coexists with true iron deficiency, making diagnosis challenging.
Clinical Features
Symptoms
Often mild and asymptomatic — discovered incidentally
Fatigue and reduced exercise tolerance (if Hb sufficiently low)
Symptoms of the underlying condition predominate
Signs
Pallor (often mild — Hb rarely drops below 80 g/L)
Signs of underlying disease (joint swelling, lymphadenopathy, etc.)
Investigations
First-line
FBCNormocytic normochromic anaemia (MCV 76-100 fL). Mild anaemia — Hb rarely <80 g/L unless combined with other causes
Iron studiesLOW serum iron, LOW TIBC (or low transferrin), NORMAL or RAISED ferritin. This is the classic exam pattern — distinguishes from IDA where TIBC is HIGH and ferritin is LOW
CRP/ESRRaised (confirms active inflammation)
Second-line
Ferritin interpretationFerritin is an acute phase reactant — may be "normal" (30-100 µg/L) despite coexisting true iron deficiency. If ferritin <100 in the presence of active inflammation, consider concurrent IDA
Soluble transferrin receptor (sTfR)Raised in true iron deficiency, NORMAL in pure ACD — useful for distinguishing ACD from coexistent IDA
Reticulocyte countLow or inappropriately normal for degree of anaemia (inadequate marrow response)
Specialist
Bone marrow biopsy with iron stainGold standard but rarely needed — shows adequate or increased iron stores in macrophages (Prussian blue stain) but reduced sideroblasts
1
Treat the underlying condition
- This is the most effective approach — anaemia improves when inflammation is controlled
- Treat RA, IBD, infection, or malignancy as appropriate
- Monitor Hb as a marker of disease activity
2
Iron supplementation
- NOT indicated in pure ACD (iron stores are adequate — the problem is sequestration)
- IV iron may be considered if coexistent true iron deficiency is confirmed (ferritin <100 with raised CRP)
- Oral iron is poorly absorbed in ACD (hepcidin blocks gut absorption) — IV route preferred if iron truly needed
3
Erythropoiesis-stimulating agents (ESAs)
- Indicated for anaemia of CKD (specific NICE guidelines: target Hb 100-120 g/L)
- Also used in anaemia of cancer, particularly chemotherapy-associated anaemia
- Darbepoetin alfa or epoetin — titrate to avoid Hb >120 g/L (increased thrombotic risk)
4
Transfusion
- Only if symptomatic severe anaemia — not for chronic mild anaemia
- Restrictive transfusion threshold (Hb <70 g/L) unless acute coronary syndrome
Complications
- Reduced quality of life: Fatigue from chronic mild anaemia
- Diagnostic confusion: May coexist with iron deficiency — interpretation requires careful assessment of ferritin in context of inflammation
- Overinvestigation: Avoiding unnecessary GI investigation for microcytic anaemia when the cause is clearly ACD
UKMLA Exam Tips
- 1The key iron studies comparison: IDA = low iron, HIGH TIBC, LOW ferritin. ACD = low iron, LOW TIBC, NORMAL/HIGH ferritin
- 2Hepcidin is the central mediator — upregulated by IL-6, blocks ferroportin, traps iron in macrophages
- 3Ferritin <100 µg/L with active inflammation (raised CRP) suggests COEXISTENT iron deficiency with ACD
- 4Do NOT give oral iron for ACD — hepcidin blocks gut absorption. If iron truly needed, give IV
- 5Hb rarely drops below 80 g/L in ACD alone — if lower, look for an additional cause
- 6sTfR raised = true iron deficiency. sTfR normal = ACD alone. Useful discriminator in combined pictures
Put your reading into practice
Topic-specific question practice is not linked for this article yet.
Choose UKMLA questions from the existing bank. General exam practice covers your selected topics; it is not filtered to this article. Your usual question-bank access applies.
Choose UKMLA practiceAfter your session, return to this section to revisit the reading and choose your next review.
Verified Sources & References
related resources
Save your place and choose what comes next
Haematology & Oncology · Article 9 of 28