Brian Payne, in a very authoritative response, declared that it can be
clinically dangerous not to make corrections and accordingly dismissed the
ionized calcium measurement as the property of choice in evaluation of the
calcium homeostasis. He gives three arguments:
Electrode junction problems,
small effects of the differences in algorithms and
poor correlation between ionized calcium and 'corrected calcium' in severely
ill patients.
Since Masters and Payne published their article on electrode junction
effects, more than a decade ago, technical achievements have been essential
and the conclusions made in the document do not seem relevant now and were
not even at that time as evident from the literature e.g. Fogh-Andersen N,
Bjerrum PJ, Siggaard-Andersen O. Ionic binding, net charge, and Donnan
effect of human serum albumin as a function of pH. Clin Chem 1993; 39: 48-52
and Fogh-Andersen N, Altura BM, Altura BT, Siggaard-Andersen O. Composition
of interstitial fluid. Clin Chem 1995; 41: 1522-5 that once and for all
describe and refute any significant protein influence and demonstrate and
illustrate the excellent agreement between the calculated and measured
Donnan effect. Intensive discussions on this matter were carried out
independently and under the auspices of the 'Expert Panel of pH and Blood
Gases' of IFCC that was active at that time.
The magnitude of the variation in the outcome of using different algorithms
is illustrated below.
The discordance between 'corrected albumin' and ionized calcium in various
diagnosis was described by Thode et al. in Scand J Clin Lab Invest
1989;49:217-223. About 15 % of the investigated 1213 patients would have
been misclassified by the 'corrected calcium'. There is no reason to believe
that the ionized calcium was the erroneous property.
More recently, Bilezikian et al. published 'Summary statements from a
workshop on asymptomatic primary hyperparathyroidism: a perspective for the
21st century' in J Bone Miner Res 2002;17:S2;N2-N11, also advocating
'corrected calcium'. The original paper was then summarized in a response
(Ionized calcium and corrected total Calcium? ibid.2003;18:1554) to a letter
to the Editor (Larsson and Magnusson. ibid. 2003;18:1554) in which the
authors criticised the Summary statements. You should read the original
papers, they are really illustrative level of the discussion. I will just
cite some passages from Bilezikian's response (ibid. 2003;18:1556) that are
all revealing:
After referring to technical and infrastructure related difficulties of the
measurements that Larsson et al. had explained as fictional Bilezikian et
al. state that their opion of the feasibility of 'corrected calcium' was
for US only and 'in those countries [that have overcome the limitations of
the ionized calcium] certainly one would opt for the ionized calcium
concentrations'. The obstacles that we have overcome e.g. in Sweden were
never specified but it seems unlikely that we should be that more advanced
than our neighbors in the west (UK and US). Many instruments have been
availble for long that allow a high throughput of ionised calcium samples.
As argued by Larsson et al. sticking to S-Calcium or 'corrected calcium'
does not comply with our obligation to improve the care of patients. An
example on the effect of the use of many different algorithms was given by
Larsson (ref above): the range of 'corrected calcium' concentration was
2,41 - 2,62 mmol/L when applied to a 'total calcium' of 2,00 mmol/L and
S-Albumin of 19 g/L. When was a difference of 0,21 mmol/L (8 %) unimportant?
A danger is with 'corrected calcium' is the false impression of reliability.
Any 'corrected calciium' would be misleading unless the used algorithm is
spelled out. A situation that is very similar to reporting results of some
hormone measurements without indicating the calibrator and method or an
expanded uncertainty without the coverage factor..
I would also like to refer to an article on preanalytical conditions that
illustrates a considerable robustness of the measurement: Kallner A
Preanalytical Procedures in the Measurement of Ioinized Calcium in Serum and
Plasma. Eur J Clin Chem Biochem 1996;34:53-58. The US fear of sending
samples by mail or courier is exaggerated unless the infrastructure is
exceptionally inefficient.
The bottom line is that even if you call it 'adjusted calcium' rather than
'corrected calcium' it is an unsuitable marker for calcium homeostasis. Many
laboratories have in fact abandoned measuring S-Calcium to the benefit of
patients and physicians.
Anders Kallner
----- Original Message -----
From: "Mike Bosomworth" <[log in to unmask]>
To: <[log in to unmask]>
Sent: Saturday, August 23, 2003 11:30 AM
Subject: Re: Corrected Calcium
I tend to agree with Trevor's answers to his own questions but would also
agree with Brian Payne, in that labs can derive their own adjustment based
upon their own data (Ann Clin Biochem 1996; 33: 55-58). I would also like to
suggest that we use the term adjusted calcium rather than corrected.
Corrected implies error in the orginal measurement.
Dr. Mike Bosomworth
Operations Manager for Pathology
Principal Biochemist
Tel. 0113 2064299 Fax 0113 2065971
Mobile 07789 174344
Please visit our web-site at www.leedsteachinghospitals.com
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