Overview

Anaemia describes the reduced ability of the blood to carry oxygen. This can be due to a reduced amount of haemoglobin and/or a reduced number of red blood cells.

Anaemia itself is not a diagnosis and underlying causes must be investigated.

Presentation

Patients with anaemia may present with:

Investigations and Classification

Initial tests

Key initial tests in anaemia can help with classifying and identifying the suspected underlying cause:

  • Haemoglobin:
    • Identifies anaemia, low
  • Mean cell volume (MCV):
    • Helps with classifying anaemia, may be low, normal, or raised
  • Reticulocyte count:
    • Assesses the bone marrow’s ability to produce new red blood cells

Classification

Anaemia can broadly be categorised based on the mean cell volume (MCV) into:

  • Microcytic anaemia – low MCV
  • Normocytic anaemia – normal MCV
  • Macrocytic anaemia – high MCV

The next tests to consider are discussed below.

Microcytic anaemia – investigations and identifying causes

Microcytic anaemia occurs due to problems with haemoglobin synthesis. This can occur due to:

The next investigations to look at are iron studies:

  • Serum iron:
    • Iron circulates as ferric (Fe3+) ions bound to transferrin
    • Serum iron is not very useful as it can be affected by diet, infection, or inflammation (may be reduced)
  • Serum ferritin:
    • This is the form iron takes when stored
    • This is a positive acute phase protein – may be falsely normal/elevated in infection or inflammation
  • Transferrin saturation:
    • This measures the number of binding sites ‘taken up’ by iron
    • Higher values suggest ‘more spots’ have been taken up, therefore, more iron in the body 
  • Total iron binding capacity (TIBC):
    • This measures the number of binding sites free for iron to bind to
    • Higher values suggest more free ‘spots’ for iron to take up, therefore, less iron in the body
    • During inflammation, the body produces less transferrin, so there are fewer free spots for binding
  • Mentzer index:
    • This is the MCV divided by the red blood cell count
    • If <13, this suggests thalassaemia

Based on these results, microcytic anaemia can be classed as follows:

  • Low iron, low ferritin, high TIBC:
    • Suggests low iron in the body, therefore IDA is likely
  • Low/normal iron, low/normal ferritin, low TIBC:
    • Suggests low/normal levels of iron in the body, but fewer spots for iron to bind to
    • This may be due to chronic inflammation leading to AOCD
  • Mentzer index <13:
    • Suggests thalassaemia is likely

Normocytic anaemia – investigations and identifying causes

Normocytic anaemia occurs when haemoglobin levels are reduced, but MCV remains normal. This can be due to:

The next investigation to look at is the reticulocyte count.

Reticulocytes are immature red blood cells and are a measure of the bone marrow’s ability to produce new red blood cells. A high reticulocyte count suggests that the bone marrow is attempting to make new red blood cells to compensate. A low reticulocyte count suggests the bone marrow cannot make enough new red blood cells. Therefore:

  • High reticulocyte counts suggest haemolysis or blood loss
  • Low reticulocyte counts suggest bone marrow suppression or failure

Further investigations can help with identifying the underlying cause. The following can be used to differentiate between haemolysis and acute blood loss:

  • Tests associated with haemolysis:
    • Bilirubin – elevated in haemolysis (bilirubin is a product of haemolysis)
    • Lactate dehydrogenase – elevated in haemolysis
    • Haptoglobins – reduced (free haemoglobin is released in haemolysis which binds to haptoglobins)

If haemolysis is likely, the next step is to determine whether the haemolysis is immune-mediated or not:

  • Direct antiglobulin (Coombs’) test:
    • Positive – immune-mediated haemolysis
    • Negative – immune-mediated haemolysis

The next step is to look at the blood film, which may show signs that correlate to a specific disorder.

Macrocytic anaemia – investigations and identifying causes

Macrocytic anaemia occurs when the MCV is raised. This can be subdivided into whether megaloblastic (enlarged and immature) red blood cells and hypersegmented neutrophils are present:

  • Megaloblastic cells present with or without hypersegmented neutrophils:
  • Megaloblastic cells not present:
    • Causes include excessive alcohol consumption, liver disease, hypothyroidism, and drugs affecting DNA synthesis such as azathioprine

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