Anaemia of chronic disease

This article is no. 3 of the anaemia series. Next article: sideroblastic anaemia. Previous article- Iron-deficiency anaemia.

Pathogenesis

The second most prevalent anaemia is anaemia of chronic disease (ACD), it is more often seen alongside chronic infections or malignancies, other causes include infections, autoimmune diseases, and transplant rejection. The pathogenesis of the condition is greatly lead by the effectiveness of the immune system, the immune response to tumour cells and pathogens is to remove and deny access to iron, which is needed to thrive. The processes are mainly thought to be mediated through cytokines such as TNF, IL-6s and IFN as well as the acute phase protein hepcidin. IL-6 is a very powerful cytokine in that it can inhibit erythropoiesis through the downregulation of gene expression; SLC4a1 reducing haemoglobin production, it increases ferratin production whilst inhibiting TNF-α, it upregulates DMT-1 which is a protein (transmembrane) involved in iron uptake in macrophages and it upregulates the production of hepcidin.

Hepicidin

Hepcidin is a peptide hormone, 25 amino acid chain protein, derived mainly from hepatic cells its synthesis is induced as a response to iron overload or inflammation, its presence crucial in the diagnosis of ACD. IL-6 induces hepcidin release from hepatocytes, upregulation causes the transport protein (ferroportin) degradation inhibiting iron absorption in duodenum enterocytes and macrophage recycling via upregulation of dMT-1 and mobilization of stored iron resulting in low iron plasma.

Clinical presentation

A patient with ACD may have low haemoglobin (Hb) and the reticulocyte index (new RBC) count may be reduced also, this is a common feature of an iron deficient anaemia. A blood film may help diagnose the underlying condition, but the red cell morphology varies greatly, less than half can be microcytic or hypochromic. Iron studies are what helps ACD stand out from the other anaemias, raised IL-6, hepcidin and ferratin are the key markers; the presence of iron results with raised ferratin and iron will be seen if a blood film is stained correctly. There may also be reduced serum iron, % saturation and TIBC. Should erythrocyte sedimentation rates be high Rouleaux’s may be seen, which are aggregations of RBC.

Conclusion

The most efficient way to diagnose an anaemia is through serum biomarkers in a FBC and iron studies. Hepcidin and other chemical markers play a key role in the diagnosis of ACD. Iron studies help to paint a clearer picture when diagnosing anaemias but should be supported with a medical history alongside a clinical examination, as comorbidities may influence chronic inflammatory markers.

By Lauren Kelly