Introduction

Anaemia of Chronic Disease (ACD) is common, particularly in the hospital setting. It occurs as a result of:

The anaemia is typically:

  • Normochromic – the concentration of Hb within each individual RBC is normal
  • Normocytic – the size of the red bloods cells themselves is within the normal range

As such, the anaemia is defined in terms of the total Hb and haematocrit.

However, it can also be:

  • Microcytic – small red blood cells
  • Hypochromic – reduced amounts of haemoglobin in each individual red blood cell

In this case may be difficult to distinguish from an iron deficiency anaemia (IDA), and in many cases, an iron deficiency anaemia may co-exist with anaemia of chronic disease.

Sometimes, anaemia of CKD is considered separately to the other causes of anaemia of chronic disease. In this artifice we will try explain where the differences arise between the causes of anaemia of chronic disease.

Other definitions

MCV – mean corpuscular volume – this tell you if it is micro / normo / macrocytic
MCH – mean corpuscular haemoglobin – this tells you if it is normo/hyper/hypo chromic
MCHC – mean corpuscular haemoglobin concentration – this is a calculation using MCV and MCH – it is not that useful!

Epidemiology

In chronic kidney disease

  • About 12% of patients will have an anaemia of chronic disease
  • This increases as the eGFR falls
  • Patients with CKD and diabetes are a greater risk of anaemia

Pathology

The anaemia is not related to bone marrow, bleeding or haemolysis, and is generally mild (Hb of 8.5-11.5g/dl).
There are varying pathologies depending on the cause.
In CKD it is though to arise from reduced renal synthesis of EPO.
In chronic inflammatory conditions, neoplasm and infection it is thought to arise from defects in iron utilisation, in particular, iron is not released from transferrin as well as normal. This seems to have an effect on erythropoiesis, and the level of EPO is reduced, although it often appears very low for such a mild anaemia. Basically – there is inhibition of erythrocyte production by cytokines.
  • The administration of EPO to patients with rheumatoid arthritis has shown to be of benefit to these patients.
  • Note that transferrin is the protein used to transport iron in the blood. It binds iron very strongly, but reversibly.
  • Ferritin is a compound that binds free iron within cells. In anaemia of chronic disease, levels of ferritin are often raised.
There are normal levels of iron stores in the bone marrow, but this, for some reason, is not released properly, and so developing erythroblasts do not receive enough of it. Therefore, the actual RBC’s will mimic those of iron deficiency anaemia.
Anaemia of chronic disease is generally a normocytic normochromic anaemia, but sometimes it can be a microcytic hypochromic anaemia.
Iron deficiency anaemia (IDA) is a microcytic hypochromic anaemia
It is thought that somewhere along this process of iron release, interferons, TNF and cytokines, such as IL-1, interfere with the release of iron.
It can be difficult to differentiate ACD from iron deficiency anaemia – they both have a low MCV. You may need to try a trial of oral iron. In ACD this will not improve the situation, but in IDA it should.
In ACD measures that treat the underlying condition will generally result in resolution of the anaemia.
You could also do an immunoassay to look at the number of serum transferrin receptors, as levels of these differ between diseases.
Anaemia
Ferritin
Iron
TIBC
Transferrin saturation
Soluble transferrin receptor
Iron deficiency
Low
Low
High
Low
High
ACD
High/Normal
Low
Low
Low
Low/normal

Normochromic – this means the concentration of haemoglobin within an RBC is normal.

Management

Treatment is generally just that of the underlying disorder. – However, in those with terminal malignancy and chronic kidney disease, you may be able to improve quality of life by giving EPO to reduce the level of anaemia. In cases of renal failure this is particularly effective as the levels of EPO are directly affected. A typical dosing regimen might include:

  • Darbepoetin alpha – given once every 2 weeks
    • Contraindicated uncontrolled hypertension
    • Side effects include:
      • Hypertension
      • Flu-like symptoms
      • Headaches
      • Increased platelets
      • Increase risk of thromboembolic events
      • Hyperkalaemia
      • Skin reactions
  • Epoetin alpha
    • An alternative drug, but less widely used due to shorter half-life, and as such requires stricter dose control and more dosage alterations
  • Iron supplementation is required for all patients on EPO agents
    • Aim for ferritin 200 – 500 ug/L
    • Transferrin saturation >20%

Treatment with EPO can reduce the need for blood transfusions – which is important in patients who may be considered for a future renal transplant

Complications

  • Anaemia puts strain on the heart, increasing the risk of left ventricular hypertrophy
  • Strongly associated with increased mortality

References

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