Anaemia of chronic disease (ACD)

Essentials

  • Exclude "specific" anaemias (iron deficiency, vitamin deficiency, haemolysis, acute haemorrhage, myelodysplastic syndrome and malignanat haematological diseases). This can be done with basic investigations of anaemia (1).
  • Assess whether the severity of the anaemia can be explained by the severity of the primary disease.
  • Avoid unnecessary iron therapy in secondary anaemia, but aim at finding those patients who would benefit from iron, i.e. who have combined anaemia.

Basis

  • A heterogeneous group of anaemic conditions
  • Pathogenesis: in anaemia associated with a chronic disease, erythropoiesis is attenuated and the utilization of iron is inhibited by mediators of inflammation and by hepcidin that regulates iron transport. Hepcidin, in a manner of speaking, "closes the ports for iron" preventing iron absorption and its release from macrophages. Usually, anaemia of chronic disease appears 1–2 months after onset of the primary disease and reflects its inflammatory activity.
  • Common in some patient groups (e.g. in severe rheumatoid arthritis and renal insufficiency (2)).
  • Is not caused by a deficiency of vitamins or mineral elements.
  • The coexistence of anaemia of chronic disease and some other type of anaemia is not uncommon.

Underlying diseases

  • Anaemia associated with a chronic disease (synonyms: anaemia of inflammation, secondary anaemia)
    • Chronic infections
    • Other chronic inflammatory diseases (autoimmune disease, severe traumas and burns)
    • Malignant tumours (without infiltrates to bone marrow)
  • "Organ-specific" causes
    • Chronic renal failure (3)
    • Cirrhosis and other liver diseases
    • Endocrinopathies (hypothyroidism, hyperthyroidism, adrenal failure, androgen deficiency, hypopituitarism, hyperparathyroidism, anorexia nervosa)

Diagnostic assessment

  • Identify the underlying disease. Include erythrocyte sedimentation rate, CRP and blood white cell count determinations in the routine laboratory examination of anaemia (the others are: haemoglobin, haematocrit, MCV and reticulocyte count).
  • Consider whether the underlying disease can explain the degree of anaemia. In moderate and mild diseases the haemoglobin concentration is usually 100–110 g/l and in more severe diseases it may be 70–90 g/l or even lower.
  • If the haemoglobin concentration is disproportionately low, search for specific causes of anaemia.
  • Exclude increased red cell loss (bleeding or haemolysis, reticulocyte count increased).
  • Exclude iron deficiency (decreased ferritin, increased plasma TfR concentration; check the reference range applied in your own laboratory), vitamin B12 deficiency and folate deficiency (MCV > 100 fl).
  • In anaemia associated with a chronic disease, red cell morphology is usually normochromic and normocytic, but becomes hypochromic and microcytic as the condition is prolonged. At this stage, the condition resembles iron deficiency anaemia.
  • Note that plasma ferritin that reflects the amount of iron storages in the tissues also acts in the same way as acute-phase proteins. Therefore, a person with inflammatory disease may have iron deficiency even if plasma ferritin concentration would be as much as 100–200 µg/l.
  • Bone marrow examination is useful in all obscure cases.
  • A patient with anaemia of chronic disease often also has other concurrent factors that contribute to the anaemia, like iron deficiency and renal insufficiency.
  • An iron therapy trial is a practical approach if iron deficiency is combined with the anaemia of chronic disease. Iron stores are restored in 2–3 months and the true level of anaemia of chronic disease is revealed. Also in this case, the assessment of the cause of iron deficiency must be kept in mind.

Treatment

  • Treat the underlying disease.
  • It is important for successful treatment to exclude the action of complicating factors such as haemorrhage, iron deficiency, vitamin deficiency, haemolysis, renal insufficiency and bone marrow effects of drugs.
  • Avoid routine administration of iron, but iron medication may be considered for a persistent inflammatory anaemia, in which case parenteral preparations are the primary choice. The best response is obtained in patients with obvious iron deficiency and low activity of inflammation.
  • Certain groups of renal or cancer patients are treated with erythropoietin (epoetin, darbepoetin alfa) according to the treatment regime chosen by a specialist.
  • Red cell transfusions are given in special cases.

Evidence Summaries


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