Hi all
I came across this document whilst inadvertently finding a "back door" into the BMJ "Best Practice" website. I've been on this forum for a while and have read all of the excellent links to various B12 articles that others have posted. I haven't seen this one before however and note that it has also been updated in March 2017.
The link is shown below, but if you click on it you will be asked to sign in (presumably GP's only), however I've found if you go to Google search and type in:-
mcv should not be used as a marker for B12 insufficiency
and then limit the search results to UK only then this will display a link to this page that will then open the full article!
bestpractice.bmj.com/best-p...
I've enclosed the full text of the article here:-
Vitamin B12 deficiency
Diagnostic approach
Traditionally, the diagnosis of vitamin B12 deficiency has relied on the finding of low serum vitamin B12 (generally, <200 picograms/mL) and clinical symptoms consistent with vitamin B12 deficiency. Unfortunately, neurological disease associated with vitamin B12 deficiency may be irreversible, and early detection can be critical in preventing permanent neurological damage. Additionally, there is no true consensus on what a normal serum vitamin B12 level should be for optimal neurological and haematological function.
Use of markers of tissue deficiency such as homocysteine, methylmalonic acid (MMA), and holotranscobalamin has improved earlier diagnosis of vitamin B12 deficiency. Optimal use of serum vitamin B12 and tissue markers is undefined, but general guidelines given here will help guide the clinician in determining whether a patient has true vitamin B12 deficiency.
At-risk groups
The clinician should take certain risk factors into account when considering who should be tested for vitamin B12 deficiency. Advancing age has increased risk. [2] [3] [4] Chronic use of medicines (specifically, metformin, proton-pump inhibitors, and anticonvulsants) can also place a patient at risk of deficiency. [22] Finally, patients with chronic GI illnesses that can cause malabsorption or inadequate absorption, including Crohn's disease and coeliac disease, and those with a history of upper GI surgery, including gastrectomy, gastric bypass, or iliectomy, should be tested for vitamin B12 deficiency.
Symptoms and signs
Patients with unexplained neurological disease (specifically, decreased vibration sense, gait abnormalities, and peripheral neuropathies) should be tested for vitamin B12 deficiency. Neuropsychiatric complaints such as depression and dementia may also clue the clinician in to an occult vitamin B12 deficiency. Late signs of vitamin B12 deficiency include angular cheilitis, glossitis of the tongue, and signs of frank anaemia and thrombocytopenia.
Initial diagnostic testing
Serum vitamin B12 remains a useful initial diagnostic test for vitamin B12 deficiency due to its widespread availability and familiarity with the test. However, caution must be used when interpreting the values, as there are no well-defined cut-offs for deficiency. [35]
Generally, serum vitamin B12 can be broken down into 3 values:
•Likely vitamin B12 deficiency: <148 picomols/L (<200 picograms/mL)
•Possible vitamin B12 deficiency: 148 to 258 picomols/L (201 to 350 picograms/mL)
•Unlikely vitamin B12 deficiency: >258 picomols/L (>350 picograms/mL).
An FBC with peripheral smear is useful to determine whether there is evidence of macrocytosis and frank anaemia, leukopenia, or thrombocytopenia. This suggests a more severe and prolonged vitamin B12 deficiency. However, a normal MCV, haemoglobin, and haematocrit are not useful to rule out tissue vitamin B12 deficiency, as many patients with vitamin B12 deficiency may have normal haematological parameters.
A peripheral smear may show the classic hypersegmented polymorphonucleated cells and megalocytes found in severe vitamin B12 deficiency with associated macrocytic anaemia, but is not sensitive to early vitamin B12 deficiency.
Serum folate level measurements were previously recommended, as low serum folate may falsely lower serum vitamin B12 levels. [36] However, in the era of folic acid fortification, concomitant folate deficiency is rare. In parts of the world where nutritional deficiencies are common, testing for concomitant folic acid deficiency and treatment can help clarify whether true vitamin B12 deficiency co-exists.
Clinical assessment of deficiency severity
The severity of the deficiency can be graded clinically as follows:
•Mild to moderate neurological manifestations: dysaesthesia/paraesthesias, polyneuropathy and depression
•Mild to moderate haematological manifestations: usually asymptomatic with normal haematocrit and high normal to mildly elevated MCV.
•Severe neurological manifestations: subacute combined spinal degeneration, dementia, or cognitive impairment. Subacute combined spinal degeneration is progressive neurological degeneration of the posterior and lateral columns of the spinal cord. Patients present with ataxia, decreased vibration sense, muscle weakness, and hyporeflexia.
•Severe haematological manifestations: pancytopenia and marked symptomatic anaemia.
Confirmatory diagnostic testing
Serum vitamin B12 <148 picomols/L (<200 picograms/mL): confirmatory treatment is generally unnecessary and empirical treatment should begin. Clinical and serological response in follow-up confirms vitamin B12 deficiency.
Serum vitamin B12 148 to 258 picomols/L (201 to 350 picograms/mL): MMA can be very sensitive for vitamin B12 deficiency but falsely high levels can occur in renal disease. Additionally, an abnormal MMA level is undefined. Patients with serum vitamin B12 in this range, together with an elevated MMA, can be considered to have probable vitamin B12 deficiency. Diagnosis is confirmed if vitamin levels normalise and serum vitamin B12 rises with adequate vitamin B12 treatment.
Homocysteine: this can be elevated with folate deficiency, hypothyroidism, and vitamin B12 deficiency. Patients with elevated homocysteine related to vitamin B12 deficiency (when folate deficiency and hypothyroidism are ruled out) should have normalisation with empirical vitamin B12 treatment.
Holotranscobalamin (hTC): this marker is being examined as a more specific marker for vitamin B12 absorption capabilities. hTC is transcobalamin bound to vitamin B12 and can be a measure of the true functional serum vitamin B12 levels. hTC may be the first marker to be detected with vitamin B12 deficiency. Levels of hTC <35 picograms/L can be consistent with vitamin B12 deficiency, and may be considered, but this test is not widely available. [37] [38] [39] [40]
Antiparietal cell antibody (APC): once vitamin B12 deficiency is confirmed, APC antibody can determine whether pernicious anaemia (PA) is the cause. This test is highly sensitive (85%) but not specific, as APC antibodies may be elevated in atrophic gastritis. [36]
Fasting serum gastrin levels: gastrin levels rise in gastric achlorhydria and can signify PA. [41]
Determining the underlying cause of vitamin B12 deficiency
Once the diagnosis of vitamin B12 deficiency is established, an aetiology should be sought. While treatment remains the same, vitamin B12 deficiency can lead the astute clinician to discover an underlying malabsorption process such as coeliac disease or Crohn's disease.
Testing for PA
•Intrinsic factor (IF) antibody is only 50% sensitive, but highly specific for PA. [36]
•Antiparietal cell antibody is highly sensitive (85%) but not specific, as APC antibodies may be elevated in atrophic gastritis. [36]
•Fasting serum gastrin levels rise in gastric achlorhydria and can signify PA. [41]
The Schilling test, the classic test to determine vitamin B12 absorption, is not in widespread use due to difficulty in performing the test and obtaining radiolabelled vitamin B12.
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The interesting bits for me were:-
"Additionally, there is no true consensus on what a normal serum vitamin B12 level should be for optimal neurological and haematological function."
"However, caution must be used when interpreting the values, as there are no well-defined cut-offs for deficiency."
•Likely vitamin B12 deficiency: <148 picomols/L (<200 picograms/mL)
•Possible vitamin B12 deficiency: 148 to 258 picomols/L (201 to 350 picograms/mL)
•Unlikely vitamin B12 deficiency: >258 picomols/L (>350 picograms/mL).
"However, a normal MCV, haemoglobin, and haematocrit are not useful to rule out tissue vitamin B12 deficiency, as many patients with vitamin B12 deficiency may have normal haematological parameters."
I realise that a lot of this advice is available from several other sources and organisations but to me this is something to refer my GP to as it is from the BMJ "Best Practice" website and they should therefore follow the guidelines !!
In my own case (B12 224) this would necessitate treatment.
Hope this helps someone!
Provider “B”-ware: Using Methylmalonic Acid Levels to Diagnose B12-deficiency Neuropathy 
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\"Function B12 Deficiency\" 
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\"Time to abandon the serum cobalamin level for diagnosing vitamin B12 deficiency\"
