To highlight the dilemma of raised troponin and what it means, below are the jumbled results of various biochemical tests including TnI. The patient is 73-year-old female presented with acute diverticulitis and possibly perforation. The tests showed severe lactic acidosis, multi-organ damage, severe hypoglycaemia, hypochlestrolaemia and hypoalbuminaemia, a picture that we commonly see when death is imminent. It represents hypoperfusion multiorgan damage most probably due to septic shock in this lady. The patient died and the SHO was asking an academic question, whether the raised troponin is part of the shock syndrome or it was due to proper coronary occlusion, my answer was: it could be either or both especially as the ECG showed non specific changes only.

Sodium 144

Potassium + 5.6

Chol 1.00

Magnesium 0.79

Urea 7.1

CK + 378

TropI + 11.05

Creatinine + 117

eGFR 44

CRP + 46

Creatinine + 117

Amylase 36

R. Glucose - 1.2

AST + 5693

GGT 7

Calcium 1.37

ALT + 4670

Albumin - 14

ALP 46

Adj.Calc. - 1.89

Bilirubin 5

Albumin - 14

pH - 6.791

pCO2 - 3.63

pO2 - 6.0

Base XS - -27.0

Act Bicarb - 3.9

O2 SAT 46.4

Sodium 140

Potassium 6.8

Lactate +15.00

Glucose -1.6

From: "Indovina, Joe [OCDUS]" <[log in to unmask]>
To: [log in to unmask]
Sent: Wednesday, 3 December, 2008 13:18:53
Subject: Re: Troponins reporting

Ian you recall correctly. Presence of circulating troponin above the 99^th percentile by itself does not indicate AMI but does indicate myocardial cell insult. After having worked with this assay for several years, it is my feeling that presence of troponin is part of a continuum of myocardial cell insult from minimal damage through to AMI. There is building data that presence above the 99^th percentile is a prognostic indicator of long term outcome.

Chris I agree with your approach and thinking in that troponin must be looked at in context. I wonder too if we have done a good enough job educating physicians. Initially troponin was discussed as a marker for AMI. As I have learned more, listened to talks, and had the opportunity to discuss and work with this assay with investigators, I now believe it is an indicator of subtle myocardial cell death yet the patient may not be at a AMI diagnosis. Other causes may be at play

What do others think?

In regards to the table, most of the vendors AMI cutoff I was able to confirm was developed on evidence of AMI. The table and the table that Dr. Jim Miller sent around was meant to show the importance (to me) of clearly identifying the expected values and method of the troponin. Numerical commutability method to method is difficult.

-----Original Message-----
From: Clinical biochemistry discussion list [mailto:[log in to unmask]]On Behalf Of IAN WATSON
Sent: Wednesday, December 03, 2008 7:37 AM
To: [log in to unmask]
Subject: Re: Troponins reporting

If I recall correctly Fred Apple talked about this at AACC this year. If above the 99^th centile that is ACS not necessarily AMI. On-admission and 6h sampling with 12 hour if on admission not raised. Values > 0.01ng/ml for Trop T meant cardiac damage and if it wasn’t rising it was chronic. According to me the LLQ for this assay is 0.03ng/ml, but he may have a super-sensitive assay. Makes sense if we could do it?

Ian

Dr Ian D Watson

Consultant Biochemist & Toxicologist

Dept Clinical Biochemistry

University Hospital Aintree

Lower Lane

Liverpool

L9 7AL

Tel +44 151 529 3575

Fax +44 151 529 3310

Fundamentals of Analytical Toxicology recently published:
http://eu.wiley.com/WileyCDA/WileyTitle/productCd-0470319356.html

From: Clinical biochemistry discussion list [mailto:[log in to unmask]] On Behalf Of SERGEANT Chris (RF4) BHR Hospitals
Sent: 03 December 2008 10:48
To: [log in to unmask]
Subject: Re: Troponins reporting

We use a testing strategy that includes the possibility of repeat analysis to observe changes in troponin concentration when diagnosis is uncertain We have advised clinicians of the manufacturers quoted 99th centile cutoff as this is the concentration, according to the guidelines, consistent with AMI. As stated below, other evidence of myocardial ischaemia is important for the diagnosis, as well as a "rise and or fall". The clinical specifity and sensitivity of the lab result is not only affected by setting the "cutoff" at the 99th centile but also the timing of the sample(s) in relation to symptoms and the reproducibility of the assay. We try to ensure clinicans do not simply see a single TNI result (often taken at varying times post symptoms) as a simple "yes" or "no" number, although this is often what they want.

Chris

-----Original Message-----
From: Clinical biochemistry discussion list [mailto:[log in to unmask]]On Behalf Of Myers Martin (LTHTR)
Sent: 03 December 2008 10:08
To: [log in to unmask]
Subject: Re: Troponins reporting

I am a little uneasy about the "AMI Cut offs" that would indicate AMI. Are these evidence based? What does an arbitary cut off, e.g. 0.1 for troponin T (at a fixed time point of 12 hr), actually mean and how would one interpret the following:

admission TnT = <0.01

12 hour troponin T = 0.09

The Expert Consensus Document, Universal Definition of Myocardial Infarction, Circulation 2007;116;2634-2653; defines a acute myocardial infarction as (amongst others) : a rise and/or fall in [troponin] with at least one level above the 99th percentile of the URL together with evidence of myocardial ischaemia (at least one of the following: symptoms, ECG changes, pathological Q wave, imaging evidence). There is not mention of another arbitary cut-off which would indicate AMI.

martin

-----Original Message-----
From: Clinical biochemistry discussion list [mailto:[log in to unmask]]On Behalf Of Indovina, Joe [OCDUS]
Sent: 02 December 2008 18:39
To: [log in to unmask]
Subject: Re: Troponins reporting

Good discussion

To help I went through my files and put together a table of different vendors troponin assay cut offs and 99% URL

I used the package insert sheets that I have and thus urge caution as some may not be 100% current

What it does show is, in my opinion, the importance of identifying on the lab report as Mohammad does

	Abbott AxSYM TnI ADV	Abbott AxSYM TnI ADV	Beckman AccuTnI	Bayer Centaur Ultra TnI	Dade RXL	DPD STAT TnI	Roche TnT	Vitros Trop I ES

AMI Cut-off	0.4	0.3	0.5	0.8	1.5	??	0.1	0.120

URL 99th Percentile	<= 0.04	0.012	<= 0.04	0.04	<= 0.05	0.2	0.01	0.034

units	ng/mL

-----Original Message-----
From: Clinical biochemistry discussion list [mailto:[log in to unmask]]On Behalf Of Mohammad Al-Jubouri
Sent: Tuesday, December 02, 2008 9:06 AM
To: [log in to unmask]
Subject: Troponins reporting

There are various cut offs used for TnT and TnI reporting. The following aucomms are added to our TnI reports (Advia Centaur TnI ultra assay) using the manufacturer's recommendations:

< 0.05 ug/L No obvious myocardial damage.

0.05 – 0.78 ug/L Myocardial damage consistent with acute coronary syndrome and/or NSTEMI

> 0.78 ug/L Myocardial damage consistent with acute MI (WHO criteria)

Always interpret TnI results within the clinical context and ECG findings.

Above comments apply to samples taken 12h post-event.

All these comments are designed to enlighten the user about how to interpret the TnI test result, however it seems that a lot of patients with positive TnI results are labelled as acute MI despite the absence of other criteria to diagnose myocardial ischaemia.

How do other people report their Troponin results?

Is there a better way of reporting lab tests using test's sensitivity/specificity and positive/negative predictive values, rather than just reporting a numerical result with a reference range of dubious origin?

Many thanks

Mohammad

From: Mohammad Al-Jubouri <[log in to unmask]>
To: [log in to unmask]
Sent: Monday, 1 December, 2008 15:54:04
Subject: Re: Troponin I - quoted cut-off value 0.10 ug/L

Richard,

We actually use 0.05 ug/L as the cut off for detecting myocardial damage (not classical MI cut off) on the Advia Centaur TnI ultra assay. As myocardial damage can be of varying aetiology ischaemic & non-ischaemic, we leave it to the clinicians to decide if the myocardial damage is due to acute coronary ischaemia or due to some other causes.

David's original statement is probably related to a recent NEQAS interpretative comment.

Best wishes

Mohammad

From: Mainwaring-Burton Richard (RGZ) <[log in to unmask]>
To: [log in to unmask]
Sent: Monday, 1 December, 2008 15:34:36
Subject: Re: Troponin I - quoted cut-off value 0.10 ug/L

THAT IS WRONG !!!

0.1 is the M.I. cutoff for TnT and NOT TnI !

I suspect that the 0.1 value may be the lowest claimed detectable for TnI

Read ALL the small print, not just the box.

I never trust what it says on the box : I keep seeing "Open Other End " - and it never is !

with best wishes
Richard
Richard Mainwaring-Burton
Consultant Biochemist
Queen Mary's Hospital
Sidcup, Kent
020-8308-3084

-----Original Message-----
From: Mohammad Al-Jubouri [mailto:[log in to unmask]]
Sent: 01 December 2008 15:05
To: [log in to unmask]
Subject: Re: Troponin I - quoted cut-off value 0.10 ug/L

I interpret it as any TnI value of 0.1 ug/L and above indicates myocardial damage, and any value < 0.1 ug/L does not indicate myocardial damage.

regards

Mohammad

Dr. M A Al-Jubouri, MB ChB, MSc, FRCP Edin, FRCPath
Consultant Chemical Pathologist

From: David Burgess <[log in to unmask]>
To: [log in to unmask]
Sent: Monday, 1 December, 2008 14:58:32
Subject: Troponin I - quoted cut-off value 0.10 ug/L

Please - how do you interpret the phrase, "Troponin I was analysed on an
Advia Centaur: quoted cut-off value 0.10 ug/L"
Regards, David.

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