Describe anaemia of chronic disease and differentiate it from iron deficiency anaemia.
Definition
Anaemia of chronic disease (anaemia of inflammation) is a mild to moderate anaemia occurring in chronic infection, inflammation or malignancy, in which iron is present but unavailable for erythropoiesis.
- The second commonest anaemia after iron deficiency, and the commonest in hospitalised patients
Causes
- Chronic infection — tuberculosis, bronchiectasis, chronic osteomyelitis, infective endocarditis, HIV
- Chronic inflammation — rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease
- Malignancy — carcinoma, lymphoma
- Chronic kidney disease — though here erythropoietin deficiency dominates
Pathogenesis
Chronic inflammation → IL-6 from macrophages → IL-6 induces hepatic synthesis of hepcidin → Hepcidin binds and degrades ferroportin, the only cellular iron exporter → Iron is trapped in macrophages and enterocytes → Reduced iron absorption and reduced release from stores → Plus shortened red cell survival and blunted erythropoietin response → A functional iron deficiency in the presence of adequate stores
- It is probably an adaptive response — withholding iron from invading organisms, which need it as much as we do; the anaemia is the price
Distinguishing It from Iron Deficiency
| Test | Iron deficiency | Anaemia OF chronic disease |
|---|---|---|
| MCV | Low | Normal, or mildly low late in the course |
| Serum iron | Low | Low |
| TIBC (transferrin) | High | Low or normal — the key difference |
| Serum ferritin | Low | Normal or high |
| Marrow iron stores | Absent | Present (indeed increased) |
| Sideroblasts | Absent | Reduced |
| Soluble transferrin receptor | Raised | Normal |
| Response to iron | Good | None |
CLINICAL PEARL
Serum iron is low in both, which is why it is useless alone. The discriminators are TIBC and ferritin, and they move in opposite directions: in iron deficiency the body is hungry for iron, so transferrin rises and ferritin falls; in chronic disease iron is being hoarded, so ferritin rises and transferrin falls. When both coexist, the soluble transferrin receptor is the most reliable test, being unaffected by inflammation.
Applied Aspects
- Treat the underlying disease — the anaemia resolves as the inflammation settles, and nothing else works reliably
- Iron is not indicated and may be harmful unless true deficiency coexists, which it often does — hence the value of the transferrin receptor assay
- Erythropoietin is effective in chronic kidney disease and in some malignancy-related anaemia, but is expensive and raises thrombotic risk
- In India, tuberculosis is the commonest cause, and an unexplained normocytic anaemia with a raised ESR should always prompt a search for it
- Transfusion is reserved for symptomatic patients, since the anaemia is usually mild and well tolerated
All questions in Haematology I: Anaemias & Red-cell Disorders
- Q1Define anaemia. Classify anaemia morphologically and aetiologically. Describe the approach to its investigation. ★
- Q2Describe the causes, stages, laboratory findings and clinical features of iron deficiency anaemia. ★
- Q3Describe megaloblastic anaemia with its causes, laboratory findings and clinical features. Differentiate B12 from folate deficiency. ★
- Q4Classify haemolytic anaemias. Describe the laboratory findings and differentiate intravascular from extravascular haemolysis. ★
- Q5Describe the pathogenesis, clinical features and laboratory diagnosis of thalassaemia. ★
- SN1Describe sickle cell disease with its pathogenesis, crises and diagnosis. ★
- SN2Describe hereditary spherocytosis with its pathogenesis, features and diagnosis. ★
- SN3Describe G6PD deficiency with its pathogenesis, precipitating factors and diagnosis. ★
- SN4Describe aplastic anaemia with its causes, features and investigations. ★
- SN5Describe autoimmune haemolytic anaemia. Differentiate warm from cold types and explain the Coombs test. ★
- SN6Describe anaemia of chronic disease and differentiate it from iron deficiency anaemia. ★
- SN7Describe the abnormal red cell shapes and inclusions seen on a peripheral smear with their significance.