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TeroPirttinen

Anaemia of Chronic Disease (Acd)

Essentials

  • Exclude acute haemorrhage, deficiencies (iron and vitamins) and haematological diseases (haemolysis, myelodysplastic syndrome, leukaemias, myeloma). This can be done with basic investigations of anaemia Assessment of Anaemia in Adults.
  • 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 prevents iron absorption from the bowel 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 Rheumatoid Arthritis and renal insufficiency Treatment of Chronic Renal Failure).
  • 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)
    • Severe obesity
  • "Organ-specific" causes

Diagnostic assessment

  • Routine laboratory examinations: complete blood count and reticulocytes, erythrocyte sedimentation rate, CRP, plasma creatinine and plasma thyrotropin
  • 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, low fasting plasma transferrin iron saturation, increased plasma TfR concentration; check the reference range applied in your own laboratory) Iron Deficiency Anaemia and vitamin B12 and folate deficiency (MCV > 100 fl) Megaloblastic Anaemia.
  • 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 is an acute-phase protein, i.e. inflammation increases blood concentration. 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 may be necessary in unclear cases, especially if other cell lines are abnormal too.
  • A patient with inflammatory anaemia may have other concurrent factors that contribute to the anaemia, like iron deficiency and renal insufficiency.
  • An iron therapy trial is a practical approach in multifactorial anaemia. Iron stores are restored in 2-3 months and the true level of anaemia of chronic disease is revealed. Remember to think about the cause of iron deficiency.

Treatment Erythropoietin for Chronic Renal Failure Anaemia, Erythropoietin or Darbepoetin for Patients with Malignant Disease

  • Good treatment of the underlying disease is also the best treatment for anaemia.
  • It is important 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. Intravenous preparations are the most effective.
  • 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.
  • SGLT2 inhibitors used in diabetes and heart failure reduce hepsidine secretion and have a positive impact on anaemia in those taking them.

    References

    • Packer M. Alleviation of functional iron deficiency by SGLT2 inhibition in patients with type 2 diabetes. Diabetes Obes Metab 2023;25(5):1143-1146 [PubMed]
    • Weiss G, Ganz T, Goodnough LT. Anemia of inflammation. Blood 2019;133(1):40-50 [PubMed]
    • Fraenkel PG. Anemia of Inflammation: A Review. Med Clin North Am 2017;101(2):285-296 [PubMed]
    • Cullis J. Anaemia of chronic disease. Clin Med (Lond) 2013;13(2):193-6 [PubMed]