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The Anaemia of Chronic Disease
Anaemia of chronic disease was established as a distinct entity in 1962.
75% clinical causes are secondary to1;
- Infection.
- Inflammation -including connective tissue disorders.
- Neoplasia
.
Anaemia is also commonly associated with chronic renal failure.
The anaemia of chronic disease is still poorly understood.
- One theory is that the anaemia results from a depressed response to erythropoietin.
- An alternative theory is that inflammation causes a change in iron recirculation, with iron
being held back in the reticuloendothelial system rather than being released to the marrow
-the 'reticuloendothelial block'. - In this case inflammatory mediators possibly interfere with the normal maintenance of iron homoeostasis, mediated by iron regulatory proteins.
- Ferritin synthesis may also be upregulated by proinflammatory cytokines,
diverting iron into the reticuloendothelial system.
The anaemia of chronic renal failure is thought to be slightly different.
- It probably results from a combination of erythropoietin deficiency and anaemia of chronic disease.2
- A further contributory factor may be the functional iron deficiency resulting from erythropoietin replacement for patients undergoing haemodialysis.
- In this situation despite adequate ferritin concentration, the erythropoietic drive outstrips the ability of the reticuloendothelial system to release storage iron quickly enough to satisfy the demands of the erythropoietin-stimulated bone marrow.
Symptoms
- Tiredness
- Pallor
- Breathlessness on exercise.
Signs
- Tachycardia
Anaemia of chronic disease typically occurs despite adequate reticuloendothelial iron stores.
- Reduced serum iron, transferrin and total iron binding capacity.
- Measuring serum ferritin is essential in investigating unexplained anaemia.
- Serum ferritin concentration is directly related to reticuloendothelial iron stores, and normally 1 μg/l serum ferritin roughly corresponds to about 8 mg of storage iron.
- Reduced serum ferritin provides unequivocal evidence of diminished iron stores and occurs in no other condition.
- Normal or raised ferritin are typical.
- In the presence of inflammation ferritin concentrations may remain normal even when reticuloendothelial iron stores are absent.
- High erythrocyte sedimentation rate.
- Red cells often normochromic, normocytic but may be hypochromic, microcytic, as frequently seen in RA and Crohn's disease.
- Bone marrow examination for iron is the definitive test for deficiency. This is very uncomfortable and expensive.
- Estimation of soluble transferrin receptor if available.
- This will differentiate microcytic anaemia of chronic disease from genuine iron deficiency when ferritin values are normal3.
- Values of both soluble transferrin receptor and the soluble transferrin receptor-ferritin index are raised in iron deficiency anaemia, but are normal or only slightly raised in anaemia of chronic disease.
- Soluble transferrin receptor concentrations have high sensitivity and specificity for identifying iron deficiency in anaemic patients with rheumatoid arthritis4.
- They are comparable to bone marrow aspiration as a diagnostic test 5.
- They are, however, five times more expensive than ferritin measurement and should be reserved for patients in whom marrow iron assessment is being considered.
Treatment of underlying condition should cause Hb to rise.
It is unresponsive to iron therapy.
Drugs
- EPO with IV or oral iron if required in chronic renal failure
- Novel erythropoiesis stimulating protein (NESP, darbepoetin alfa) stimulates erythropoiesis by the same mechanism as recombinant human erythropoietin (rHuEPO) but it is biochemically distinct.
It has a 3-fold greater serum half-life and can maintain haemoglobin levels as effectively as rHuEPO in anaemic patients with chronic renal failure with less frequent dosing. - Also consider in RA6 and cancer7.
- In temporal arteritis or polymyalgia rheumatica, hypochromic microcytic anaemia with dysproteinaemia can be treated with prednisolone and maintained on low dose steroids8.
Document References
- Fitzsimons EJ, Brock JH; The anaemia of chronic disease.; BMJ. 2001 Apr 7;322(7290):811-2.
- Nissenson AR, Strobos J; Iron deficiency in patients with renal failure.; Kidney Int Suppl. 1999 Mar;69:S18-21. [abstract]
- Punnonen K, Irjala K, Rajamaki A; Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency.; Blood. 1997 Feb 1;89(3):1052-7. [abstract]
- Suominen P, Mottonen T, Rajamaki A, et al; Single values of serum transferrin receptor and transferrin receptor ferritin index can be used to detect true and functional iron deficiency in rheumatoid arthritis patients with anemia.; Arthritis Rheum. 2000 May;43(5):1016-20. [abstract]
- Fitzsimons EJ, Houston T, Munro R, Sturrock RD, Brock JD. Erythroblast iron metabolism and serum transferrin receptor in anaemic patients with rheumatoid arthritis. Blood 1998; 92: 325a.
- Peeters HR, Jongen-Lavrencic M, Bakker CH, et al; Recombinant human erythropoietin improves health-related quality of life in patients with rheumatoid arthritis and anaemia of chronic disease; utility measures correlate strongly with disease activity measures.; Rheumatol Int. 1999;18(5-6):201-6. [abstract]
- Smith RE Jr, Jaiyesimi IA, Meza LA, et al; Novel erythropoiesis stimulating protein (NESP) for the treatment of anaemia of chronic disease associated with cancer.; Br J Cancer. 2001 Apr;84 Suppl 1:24-30. [abstract]
- Hume R, Dagg JH, Goldberg A; Refractory anemia with dysproteinemia: long-term therapy with low-dose corticosteroids.; Blood. 1973 Jan;41(1):27-35.
DocID: 827
Document Version: 20
DocRef: bgp988
Last Updated: 10 Jul 2006
Review Date: 9 Jul 2008
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