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    Ionized Versus Albumin-Adjusted Total Calcium | AACC.

    org 11/3/22 5:27 pm

    All Articles

    Ionized Versus Albumin-


    Adjusted Total Calcium
    Ask the Expert: June 2019

    Author: Tahir Pillay, MBchB, PhD, FRCPath, FCPath //


    Date: JUN.1.2019 // Source: Clinical Laboratory News

    Topics: Analytes, Analytical Techniques and Applications,


    Electrolytes

    WHY DO LABS CORRECT TOTAL CALCIUM


    BASED ON ALBUMIN?
    A: Ionized calcium is the most accurate test for assessing a
    patient’s calcium status, but its application remains limited.
    Clinical laboratories were not able to broadly use the first
    method developed for measuring ionized calcium because it
    was based on a bioassay requiring frog tissue. Following the
    introduction of direct potentiometry with ion-selective
    electrodes (ISE), the availability and precision of ionized
    calcium measurement has improved, but preanalytical and
    analytical challenges still hamper its universal application.
    These include issues related to sample handling, cost,
    equipment maintenance, analytical performance, and lack of
    measurement standardization.

    In light of this, the International Federation of Clinical


    Chemistry and Laboratory Medicine (IFCC) states that total
    calcium measurement may be used as a surrogate for
    ionized calcium in patients who do not have protein and pH
    abnormalities. Labs can measure total calcium using ISE,
    atomic absorption spectrophotometry, or photometric
    methods employing metallochromic indicators or dyes such
    as o-cresolphthalein complexone and arsenazo III. However,
    the correlation between ionized calcium and total calcium can

    https://www.aacc.org/cln/articles/2019/june/ionized-versus-albumin-adjusted-total-calcium Page 1 of 3
    Ionized Versus Albumin-Adjusted Total Calcium | AACC.org 11/3/22 5:27 pm

    be compromised by alterations in albumin concentration,


    blood pH, elevated levels of drugs or fatty acids bound to
    albumin, and unusual serum proteins such as monoclonal
    immunoglobulins. This is a major drawback of total calcium
    measurement, especially in hospitalized patients.

    To overcome this, various nomograms and formulae have


    been developed to estimate ionized calcium by correcting
    total calcium for total protein, albumin, globulins, and pH. The
    most widely used of these is the Payne et al. formula:
    Adjusted calcium (mmol/L) = Total calcium (mmol/L) + 0.02
    [40 – serum albumin (g/L)]. This and other correction
    formulae were derived by determining the linear regression
    relationship of serum calcium to albumin concentration in
    healthy patients.

    WHAT ARE THE SHORTCOMINGS OF USING


    CORRECTION FORMULAE?
    The Payne formula and related equations were derived
    decades ago using the bromocresol green (BCG) method for
    albumin measurement. Since then, however, analytical
    techniques for albumin measurement have changed. BCG
    overestimates serum albumin because of nonspecific dye
    binding with many proteins, particularly at low serum albumin
    concentrations, so a large proportion of labs now use the
    more effective bromocresol purple (BCP) method. If a lab
    uses the BCP method, this can affect the performance of
    BCG-based equations. Studies also show that the Payne
    formula correlates poorly with ionized calcium in specific
    patient populations such as critically ill surgical patients, renal
    failure and hemodialysis patients, primary
    hyperparathyroidism patients, and very elderly hospitalized
    patients. For these cases, BCP-specific and other alternative
    formulae have been developed, but experts recommend that
    labs use ionized calcium for the most accurate results.

    HOW SHOULD LABS APPROACH CALCIUM


    MEASUREMENTS?
    Taking all of this into account, there are several ways
    laboratories can handle calcium measurements. Labs may
    elect to measure ionized calcium in all samples. In some
    countries this is standard practice, although technical
    reasons may hinder this approach. If choosing this route, labs
    can refer to recommendations provided by the IFCC on using
    ISE to determine ionized calcium in whole blood, plasma, and
    serum, as well as on sampling, transport, and storage for this
    test. These recommendations emphasize rapid analysis of an
    anaerobic sample placed on ice to counteract various causes
    of pH alteration, which impacts the concentration of ionized

    https://www.aacc.org/cln/articles/2019/june/ionized-versus-albumin-adjusted-total-calcium Page 2 of 3
    Ionized Versus Albumin-Adjusted Total Calcium | AACC.org 11/3/22 5:27 pm

    calcium. The IFCC also cautions labs to avoid dilution effects


    from anticoagulant solutions such as heparin.

    On the other hand, if testing all samples for ionized calcium


    proves to be too difficult, labs might elect to measure ionized
    calcium only in specific patients for whom there is a clear
    clinical indication. For all other patients, labs can report
    albumin-adjusted total calcium, with the caveat that—given
    the differences in the performance of published correction
    equations—each laboratory should derive its own equation
    for correcting total calcium based on albumin.

    Tahir S. Pillay, MBChB, PhD, FRCPath, FCPath, is chief


    specialist, professor, and head of the department of chemical
    pathology at the University of Pretoria in South Africa.
    +Email: [email protected]

    https://www.aacc.org/cln/articles/2019/june/ionized-versus-albumin-adjusted-total-calcium Page 3 of 3

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