THE VITAMIN B12 AND FOLATE PATHOLOGY INVESTIGATION
THE INVESTIGATION OF ERRORS IN PATHOLOGY TESTS
FOR VITAMIN B12 AND FOLATE DEFICIENCY
BY MEANS OF MEDICAL EXPERIMENTS
THE SERUM VITAMIN B12 INVESTIGATION
SERUM B12 ERRORS
Summary
Laboratory Performance
Sullivan Nicolaides
Interpretation Errors
Immunoassays

Index

This page contains the following sections:

You can go to a section by selecting the link.

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Introduction

Here you will find my specific claims about what I consider to be the poor performance by Sullivan Nicolaides Pathology, Brisbane (SNP).

For each issue raised, I explain:

  • What Went Wrong
  • Why it Matters

Notes for Charts and Tables

Where a chart is shown, you can view a larger chart in a new window by selecting the link shown above the chart.

Where there is a link to a table, above a chart, you can view the complete Excel table in a new window.

Tables will initially appear at low resolution in the new window. To enlarge the table to full size, move the cursor from the white space below the table to inside the lower right corner of the table; an icon will then appear in the lower right corner of the table. Click on the icon to view the table full-size. Use the horizontal scroll-bar, in the new window, to view the entire table.

The chart and table numbers used here correspond to the sheet numbers in the Excel file, Series 1 - Serum B12 Investigation, which may be downloaded from Evidence.

These results can be verified from the scanned original pathology reports, available on this site from Evidence.

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SNP B12 - Use of Incorrect "Normal" Level

Summary of what went wrong

Sullivan Nicolaides Pathology incorrectly quotes a "normal" level of >130 pmol/L for serum vitamin B12:

A level of 130 pmol/L is not considered normal by experts, reference DA01 to DA10, and a level below 295 pmol/L should be considered suspicious of B12 deficiency in the presence of symptoms. This is clear in the flowchart from Oh and Brown, reference DA01:

Oh and Brown

It is also clearly stated in the Abbott AxSym B12 Package Insert, reference AD01, supplied with the instrument used by Sullivan Nicolaides Pathology:

A serum B12 cut-of level of 200 pmol/L, for defining B12 deficiency, is recommended by Clarke et al, reference DA04.

Why it Matters

Sullivan Nicolaides Pathology failed to report the onset of an actual vitamin B12 deficiency that should have been interpretable from their serum B12 results...

As my serum B12 level fell, after I ceased taking the oral B12, my MMA levels increased during 2006. Here is a chart showing the relationship between my serum B12 measured by SNP, and MMA measured by Westmead:

Chart C24 Table C8

My MMA level exceeded the Westmead (CHW) cut-off, of 0.34 umol/L, between 24 February (Day 114) and 5 June 2006 (Day 215). This means that I was becoming vitamin B12 deficient, by the very latest, after 5 June 2006.

According to experts, methylmalonic acid is a sensitive and selective marker of vitamin B12 deficiency. Some excellent articles on this can be found by selecting reference DA0 to DA10.

After ceasing taking the oral B12, my serum B12 level rapidly fell to 323 pmol/L, in mid-March 2006, then fell much more slowly to a minimum of 140 pmol/L in October 2006. The anomalous peak on 9 October will be considered separately in the next section.

During 2006, my B12 level did not fall below the "normal" level of >130 pmol/L quoted by Sullivan Nicolaides in their reports, so they did not report a vitamin B12 deficiency..

There is clearly a problem when the Westmead MMA results unambiguously indicate the onset of vitamin B12 deficiency, whereas the SNP serum B12 results remain "normal" and do not even enter their quoted "borderline range".

For a detailed investigation of the reference Intervals and limits, select Reference Intervals and Limits under Interpreting Results.

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SNP B12 - Misleading Comments in Reports

Summary of what went wrong

The report SNP reports use the heading Anaemia Profile for the B12 results, and include the comment "but unexplained low levels do occur in some patients without B12 deficiency".

Why it Matters

The heading Anaemia Profile is misleading because anaemia is not present in 30% of cases of vitamin B12 deficiency. This is very well documented in many of the references cited here; an excellent example is the article by Lindenbaum et al, reference CA12.

The comment "but unexplained low levels do occur in some patients without B12 deficiency", is true but very misleading because the quoted SNP "normal" and "borderline" levels are far too low. B12 deficiency can also occur in patients with high levels of serum B12, but this is not commented on in the reports.

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SNP B12 - Anomaly in Results

Summary of what went wrong

On 30 October 2006, we received an anomalous result for my serum vitamin B12 test from Sullivan Nicolaides Pathology.

According to the SNP result for 30 October, my B12 level increased from 169 pmol/L to 250 pmol/L in one week. As I was not taking any supplements, and am on a very strictly controlled vegetarian diet, there was nothing to drive my serum B12 level higher.

Here is a chart showing the anomaly:

Chart C11 Table C8

You will see that it appears that my levels fell gradually to a low of 140 pmol/L on 16 October, then climbed to a peak of 250 pmol/L on 30 October, then fell again to a low of 143 pmol/L. There is no reasonable explanation for this other than very significant analytical error. The rapid increase in B12 level after 13 November was caused by me re-starting B12 therapy.

With a claimed SD (Standard Deviation) of 18 pmol/L, an error of 110 pmol/L represents about 5 SD, placing it outside the 99.9999% confidence interval. The spike in B12 level cannot be explained as being within normal error limits; something is seriously wrong.

I believe that this episode is an example of problems with calibration, and control ranges. For more details select Control Ranges - Open to Abuse under Immunoassays.

Why it Matters

There is a totally different interpretation for the result of 250 pmol/L compared to a result of 140 pmol/L. This potentially has very serious implications for other patients, if their results contain similar errors.

In the absence of any symptoms, a result of 250 pmol/L would not require further investigation, according to the criteria given in the Abbott AxSym B12 Package Insert, reference AD0C1, whereas a result of 140 pmol/L would be considered abnormal.

A result of 140 pmol./L satisfies the criteria for vitamin B12 deficiency, as defined by Clarke et al, reference DA04.

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