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Question answered:09/06/08
CKS guidance on Anaemia - B12 and folate deficiency has a section on Investigations for diagnosis (1). This states:
§ Check the full blood count.
§ If the haemoglobin level is low and the mean cell volume (MCV) is high, check serum vitamin B12 and serum folate concentrations.
o Red cell folate can also be used to screen for folate deficiency, but is more difficult to interpret than serum folate.
§ If the haemoglobin level is low and the MCV is normal or low, check ferritin, vitamin B12, and folate levels.
o Conditions such as iron deficiency anaemia or thalassaemia trait can mask the development or presence of macrocytosis.
o For more information, see the CKS topic on Anaemia - iron deficiency.
§ Generally the diagnosis should rely on the clinical situation and the vitamin B12 and folate levels. A blood film may be useful in certain cases if there is diagnostic uncertainty. Discuss with a haematologist before requesting.
§ Consider requesting liver function tests, gamma-glutamyl transpeptidase, and/or thyroid function tests if other causes of macrocytosis (e.g. alcohol excess, hypothyroidism) are suspected.
The document also has a section:
How should I investigate a person with vitamin B12 deficiency anaemia in primary care?
§ Determine whether there is an underlying cause for the vitamin B12 deficiency.
o Check serum anti-intrinsic factor and anti-parietal cell antibodies.
§ Determine whether the person has experienced complications of anaemia, or of vitamin B12 or folate deficiency.
Clarification / Additional information
§ Anti-intrinsic factor antibody is extremely specific for pernicious anaemia, but has a low sensitivity (50%). Around half of people with pernicious anaemia will have anti-intrinsic factor antibody [Andres et al, 2004; Longmore et al, 2007]. If anti-intrinsic factor antibody is present, pernicious anaemia is very likely, but its absence does not rule out a diagnosis of pernicious anaemia.
§ Anti-parietal cell antibody is found in 90% of people with pernicious anaemia, but also in 3–10% of people without it [Longmore et al, 2007]. The sensitivity of anti-parietal cell antibody for pernicious anaemia is more than 90%. However, its specificity is 50%, which is much lower than that of anti-intrinsic factor antibody [Andres et al, 2004]. If anti-parietal cell antibody is not present it is unlikely that the person has pernicious anaemia, but its presence is not diagnostic as it can occur in other conditions (e.g. atrophic gastritis) and older people (16% of normal women over 60 years of age) [Carmel, 1992; Hoffbrand et al, 2006].
Basis for recommendation
§ This recommendation is based on an article on macrocytic anaemias in the ABC of Clinical Haematology [Hoffbrand and Provan, 2007].
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