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Dear all
Apologies in advance.
Will not speaking specifically to all areas, there are system design advantages to running P to L. Years ago, measuring at 340 nm for assays that generate very little signal was a challenge. This was clearly evident in transaminase assays such as AST and ALT. LDH was in the same category in that L to P was a slower rate leading to low signal. Assays with little signal had precision issues at the low end due in part to noise of the reading system. Laboratories at that time complained of the low end precision and lack of (dare I say) low end ‘sensitivity’.
Assay design chemists faces how to overcome the signal to noise issue. Rrunning P to L increased the signal and improved low end performance substantially. It was also found that upper end linearity did not suffer nor did one have to increase the NADH levels. Reagent stability was also found to be improved.
This work for some assay design chemists was built in part from prior recommendations provided by the Scandinavian Committee of Enzymes in the early 1970’s in which the P to L reaction was discussed and proposed.
When P to L methods were then introduced in the back in the late 1970’s and early 1980’s, I recall this very discussion of harmonization. Labs were very pleased with the improved performance. Back then the idea was to move everyone to P to L.
Interesting how the discussion has come 180 degrees. The differences of P to L vs L to P are in fact based on very clear assay/system challenges that were and remain far from arbitrary.
Hope this bit helps explain some of the history as to how we got here.
Good discussion.
Joe I
From: Clinical biochemistry discussion list [mailto:[log in to unmask]] On Behalf Of Myers Martin (LTHTR)
Sent: Tuesday, September 11, 2012 8:11 AM
To: [log in to unmask]
Subject: Re: Lactate Dehydrogenase
David
I do not think that you are being provocative. Indeed I agree that you should have done something about it 20 years ago!
How can it make sense that in the UKNEQAS return for august 2012, there were 182 labs performing P to L methods and 179 labs performing L to P methods. Different ref ranges and unnecessary confusion amongst the users- differences probably based on flimsy and arbitrary evidence and opinions. Once again I agree with you that we have a collective professional responsibility to resolve these essentially arbitrary choices made by laboratarians.
Applying Newton's First law to Laboratarians shows that folk will resist change unless an external force is applied. We need an external force.
A challenge! If you have the evidence then why not post a list of assays that you think need "sorting", so that we can start the debate with providers and the diagnostics industry and pass the consensus recommendations to national bodies.
Martin
Ps just did a spell check and it did not like UKNEQAS, and recommended UNEASY
-----Original Message-----
From: Clinical biochemistry discussion list [mailto:[log in to unmask]] On Behalf Of David Bullock
Sent: 10 September 2012 20:32
Subject: Lactate Dehydrogenase comparability
Martin:
I'm gratified by your personal support for my advocacy for adoption of a single method principle across the UK, to facilitate comparability of all results submitted to the EPR and other cumulative patient records. This was included in our report to CfH/DH on the validity of combining data (accessable through birminghamquality.org.uk - this demonstrates how UK NEQAS experience can inform national practice), but had to be classified as a responsibility of professional societies
Unfortunately, there appears to be no clear route to get such recommendations forcibly to the attention of DH/CfH/NLMC/etc with a view to national implementation, despite what I believe to be substantive patient safety issues:
- can responsible individuals (eg Paul, Gifford & Ian) take this forward themselves in their designated professional roles?
- do the ACB Scientific Committe or Clinical Practice Division have a formal input route?
- what can the National Quality Assurance Advisory Panel and Joint Working Group (ie Pat, Tim & David) do through RCPath? I'm fairly sure Archie Prentice would facilitate such communications in the interests of national comparability of patient care
- can BIVDA (though Doris-Ann) confirm that all members have reagents available that comply, and if not what can be done to resolve the situation?
- has Pathology Harmony (over to you, Jonathan!) ever considered this issue? If PH can firmly advocate the minority practice of reporting haemoglobin in g/L, why not adoption of a two-thirds or even one-third practice (UK NEQAS can provide you with evidence on the national picture) for enzyme activity assays?
To be fully effective, this must be a collaborative effort - and similar issues also arise for PyrP inclusion in AST/ALT assays and buffer selection in ALP assay. We have a collective professional responsibility to resolve these essentially arbitrary choices
Best wishes, and no apologies whatsoever for being provocative
David
Organiser, UK NEQAS for Clinical Chemistry and Director, Birmingham Quality
PS1: If I was feeling jaundiced, I'd suggest UK NEQAS could have driven these initiatives 20 years ago if only Margaret Thatcher hadn't intervened with the mantra of "competition, even at the expense of comparability" . . .
PS2: [with tongue very firmly in cheek] Remembering my classical chemistry education, perhaps we could best enlist SoS support by expressing all recommendations as being valid "at ultimate dilution" . . .
________________________________
From: Clinical biochemistry discussion list [[log in to unmask]] On Behalf Of Myers Martin (LTHTR) [[log in to unmask]]
Sent: 10 September 2012 18:59
Subject: Re: Lactate Dehydrogenase
the counts are in!
There is an IFCC "reference" method: L to P The best LDH method as a tumour marker is L to P (Tietz and others).
I agree with David Bullock we should use just one method It would appear that L to P is the method of choice and for patient safety reasons we should all use L to P.
martin
________________________________
From: Clinical biochemistry discussion list [mailto:[log in to unmask]] On Behalf Of Myers Martin (LTHTR)
Sent: 05 September 2012 11:36
Do people have a view on whether lactate dehydrogenase should be measured by lactate to pyruvate or pyruvate to lactate, especially if the LDH assay is primarily being used as a tumour marker?
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