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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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1437-4331
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Volume 56, Issue 1

Issues

Handling the altered test results of hemolyzed samples. Recommendations of the Quality, Management, Safety and Evidence Committee (CCGSE) of the Spanish Association of Medical Biopathology and Laboratory Medicine (AEBM-ML)

Daniel Pineda-Tenor
  • Corresponding author
  • Comité de Calidad, Gestión, Seguridad y Evidencia (CCGSE) de la Asociación Española de Biopatología Médica – Medicina de Laboratorio (AEBM-ML); and Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain
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/ Enrique Prada de Medio
  • Comité de Calidad, Gestión, Seguridad y Evidencia (CCGSE) de la Asociación Española de Biopatología Médica – Medicina de Laboratorio (AEBM-ML); and Hospital Virgen de la Luz, Cuenca, Spain
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/ Pedro María Belinchón Torres
  • Comité de Calidad, Gestión, Seguridad y Evidencia (CCGSE) de la Asociación Española de Biopatología Médica – Medicina de Laboratorio (AEBM-ML); and Complejo Hospitalario Infanta Cristina, Badajoz, Spain
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/ Félix Gascón Luna
  • Comité de Calidad, Gestión, Seguridad y Evidencia (CCGSE) de la Asociación Española de Biopatología Médica – Medicina de Laboratorio (AEBM-ML); and Hospital Valle de los Pedroches, Pozoblanco, Córdoba, Spain
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/ Luis Javier Morales García / María del Carmen Lorenzo Lozano
  • Comité de Calidad, Gestión, Seguridad y Evidencia (CCGSE) de la Asociación Española de Biopatología Médica – Medicina de Laboratorio (AEBM-ML); and Hospital Santa Bárbara, Puertollano, Spain
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/ María Pacheco Delgado
  • Comité de Calidad, Gestión, Seguridad y Evidencia (CCGSE) de la Asociación Española de Biopatología Médica – Medicina de Laboratorio (AEBM-ML); and Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain
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/ Ana Cosmen Sánchez
  • Comité de Calidad, Gestión, Seguridad y Evidencia (CCGSE) de la Asociación Española de Biopatología Médica – Medicina de Laboratorio (AEBM-ML); and Hospital Santa Bárbara, Puertollano, Spain
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/ Santiago Prieto Menchero
  • Corresponding author
  • Comité de Calidad, Gestión, Seguridad y Evidencia (CCGSE) de la Asociación Española de Biopatología Médica – Medicina de Laboratorio (AEBM-ML); and Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain
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/ María Ángeles Cuadrado Cenzual
  • Comité de Calidad, Gestión, Seguridad y Evidencia (CCGSE) de la Asociación Española de Biopatología Médica – Medicina de Laboratorio (AEBM-ML); and Hospital Clínico San Carlos, Madrid, Spain
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Published Online: 2017-06-16 | DOI: https://doi.org/10.1515/cclm-2017-0354

To the Editor,

Hemolysis is one of the most frequently occurring problems in the clinical laboratory and is a primary reason for rejecting samples [1, 2]. According to the current consensus, results that have been altered by hemolytic events should be discarded [3, 4]. Various researchers have proposed using mathematical algorithms to correct for the error caused by hemolysis and thereby estimate the result, but the use of corrected data from a distorted sample is risky because it may be misinterpreted by the clinic [5].

Recently, Cadamuro et al. [6] looked at the problem from a different point of view, pointing out that a clinic often does not need an exact result. Sometimes an approximation suffices to guide a diagnosis or make a clinical decision. For this reason, one possibility being explored is substituting the distorted result in a report with a text such as “see comments”. The altered results can then be documented in the comments section of the report along with information about why the data has been rejected, the level of hemolysis, specific cut-off values for each parameter, and whether or not the values are artificially inflated or reduced [6]. Lippi et al. [7] have studied the problem and subscribe to the previously published recommendations. They point out that “suppressing data in unsuitable (hemolyzed) samples and promptly notifying the clinicians by direct contact about the need to recollect the sample and repeating laboratory testing probably remains the most (clinically and analytically) viable and safe practice” [7].

The Quality, Management, Safety and Evidence Committee (CCGSE) of the Spanish Association of Medical Biopathology and Laboratory Medicine (AEBM-ML) have developed a set of recommendations which have been published and endorsed by three Spanish clinical laboratory associations: the AEBM-ML, the AEFA, and the SEQC [5] (Figure 1).

Summary of the recommendations proposed by the CCGSE AEBM-ML and a procedural flowchart to handle the altered test results from hemolyzed samples.
Figure 1:

Summary of the recommendations proposed by the CCGSE AEBM-ML and a procedural flowchart to handle the altered test results from hemolyzed samples.

As a general rule, it is not advisable to report a result that is distorted by hemolysis, whether a direct analytical result or a corrected one. An exception to this rule can be made when the hemolysis is found at a clinically insignificant level. Below are the recommendations that have been made for the following concrete situations:

Recommendation 1: Preventive action. Before establishing the use of corrective algorithms, a clinical laboratory should have the mechanisms in place needed to minimize, as much as possible, the pre-analytical errors that lead to hemolysis. This should include training the staff responsible for sample extraction and handling. These mechanisms should also include the development of a pre-analytical workflow that allows for suitable sample transport, storage, and processing.

The clinical laboratory should be able to identify phlebotomy services and professionals that have an excessive error rate and take steps to minimize this source of error (in the cases where the country works council allow to track the personal error rates).

It is advisable for the clinical laboratory to incorporate the following type of quality indicator as part of its quality control system “number of hemolyzed samples/total number of samples in which hemolysis was measured”. The quality control system should keep track of pre-analytical errors and exhaustively control and monitor the entire process. In this context, we recommend the inspiration of the IFCC project from the IFCC Working Group on Laboratory Errors and Patient Safety (IFCC WG-LEPS), which aims to standardize quality-indicators [8], which is complemented with the free software for recording these preanalytical errors [9].

Recommendation 2: Before applying a corrective equation, each laboratory should calculate its own regression line coefficients or otherwise perform its own validation of the algorithm. The corrective algorithms found in the literature are usually based on regression lines developed under specific laboratory conditions. Every laboratory has its own types of analyzers, reagents, calibration methods, and personnel. This means that, even if an equation is based on a sensible experimental design and has been optimized by the group that designed it, this algorithm cannot be applied “as is” in another laboratory. The equation needs to be validated in every laboratory in which it is employed. Providing a detailed explanation of how to design or validate equations is not one of the objectives of this document, but in general terms there are two possible options for adopting corrective equation.

Option 1: A clinical laboratory can design its own equation (recommended). The parameters of the regression line can be calculated by replicating the accepted and validated empirical methods of a previously published study. We consider that a value of R2≥0.95 indicates an adequate model-data fit.

Option 2 (acceptable): Verify that the results of measuring hemolyzed serum/plasma samples followed by application of an equation coincide with the results of measuring the same samples in the absence of any distortion. In this case, we recommend to use at least 40 pairs of hemolyzed/non-hemolyzed samples, including a sample set representative of the full range of hemolysis that the equation is meant to cover. A result that is estimated by the equation is acceptable when it differs from the with the non-hemolyzed result by an amount that is less the total acceptable error as defined by the laboratory for the determination in question. For example, that difference has to be <5.61% for potassium or 11.4% for LDH according to the desirable specification based on biological variation [10]. In order for the verification to be approved, at least 95% of the estimated results have to be acceptable.

Recommendation 3: Under no circumstances should the values estimated by the corrective equation be reported. It is advisable to include a comment in the laboratory report as a guide for the petitioning clinic. Possible approaches to a variety of situations follow below. These approaches depend on the level of hemolysis in the sample.

3.1 Lightly hemolyzed samples. A sample is considered lightly hemolyzed when the level of distortion does not exceed the reference change value or bias percentage cutoffs based on the analytical quality specification, such as biological variation ADDIN EN.CITE ADDIN EN.CITE.DATA [10]. The uncorrected value can be reported because the deviation from the “true value” is less than delta check or allowed bias and consequently do not significantly impact among the clinical interpretation.

3.2 Hemolyzed samples that are suitable for correction. Some samples have a level of hemolysis that significantly changes the result and that falls within the limits of the equation. For directions on how to proceed, potassium measurements are used as an example (additional comments should be designed for another altered tests).

If the corrected values fall below the reference range for potassium, discard the original result and add the following comment:

Hemolyzed serum or plasma. A new sample is requested for the evaluation of the concentration of potassium. Having applied the corrective algorithm that is based on statistical methods, the result suggests the possibility of hypokalemia. A clinical evaluation of the patient is recommended. Please provide a new sample as soon as possible.

If the corrected values fall within the reference range for potassium, discard the original result and add the following comment:

Hemolyzed serum or plasma. Having applied the corrective algorithm that is based on statistical methods, the result suggests that the level of potassium falls within the reference range. A clinical evaluation of the patient is recommended. Please provide a new sample in the case there is a discrepancy in the state of the patient’s health and the estimated result.

If the corrected values fall above the reference range for potassium, discard the original result and add the following comment:

Hemolyzed serum or plasma. A new sample is requested for the evaluation of the concentration of potassium. Having applied the corrective algorithm that is based on statistical methods, the result suggests the possibility of hyperkalemia. A clinical evaluation of the patient is recommended. Please provide a new sample as soon as possible.

If the corrected values reveal a critical level of potassium, eliminate the original result. It is advisable to contact the clinic by phone according to the protocol established by the laboratory for handling critical/panic values. Include the following comment:

Hemolyzed serum or plasma. A new sample is requested for the evaluation of the concentration of potassium. Having applied the corrective algorithm that is based on statistical methods, the result suggests the possibility of severe hyperkalemia. A clinical evaluation of the patient is recommended. Please provide a new sample as soon as possible.

The levels of hemolysis and the range of valid corrections must be clearly defined by the laboratory.

3.3 Hemolyzed samples outside the range of the equation. A correction cannot be applied. The original result should be discarded without being corrected. A new sample should be requested.

If a laboratory does not employ corrective equations, the altered, uncorrected results should not be reported either. However, they should be interpreted. The same procedure should be followed as outlined in recommendation 3. Nevertheless, in the absence of a corrected approximation, the interpretation should be done by a laboratory professional with a high level of expertise.

In summary, the information is more important than data. If the reason for requesting an analysis is urgent and/or the patient is at risk, the possibility of testing a sample other than the one available needs to be considered. The petitioner should be contacted directly in order to explain the problem and to discuss whether a new sample should immediately be provided. In any case, the laboratory must advise to correctly understand the interferences, to prevent it occurrence and to adequate interpretation of the obtained results.

References

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    Lippi G, Blanckaert N, Bonini P, Green S, Kitchen S, Palicka V, et al. Haemolysis: an overview of the leading cause of unsuitable specimens in clinical laboratories. Clin Chem Lab Med 2008;46:764–72. PubMedWeb of ScienceGoogle Scholar

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    Simundic AM, Topic E, Nikolac N, Lippi G. Hemolysis detection and management of hemolysed specimens. Biochem Med 2010;20:154–9. Google Scholar

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    Pineda Tenor D, Prada de Medio E, Belinchón Torres PM, Gascón Luna F, Morales García LJ, Lorenzo Lozano MC, et al. Recomendación del uso de ecuaciones de corrección de valores de potasio en presencia de interferencia por hemólisis. Rev Lab Clin 2016;9:177–83. Google Scholar

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    Cadamuro J, Mrazek C, Haschke-Becher E, Sandberg S. To report or not to report: a proposal on how to deal with altered test results in hemolytic samples. Clin Chem Lab Med 2017;55:1109–11. Web of SciencePubMedGoogle Scholar

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    Lippi G, Cervellin G, Plebani M. Reporting altered test results in hemolyzed samples: is the cure worse than the disease? Clin Chem Lab Med 2017;55:1112–4. Web of ScienceGoogle Scholar

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    Sciacovelli L, Lippi G, Sumarac Z, West J, Garcia Del Pino Castro I, Furtado Vieira K, et al. Quality indicators in laboratory medicine: the status of the progress of IFCC working group “laboratory errors and patient safety” project. Clin Chem Lab Med 2017;55:348–57. Web of ScienceGoogle Scholar

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    Lippi G, Sciacovelli L, Simundic AM, Plebani M. Innovative software for recording preanalytical errors in accord with the ifcc quality indicators. Clin Chem Lab Med 2017;55:e51–3. Web of SciencePubMedGoogle Scholar

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    Ricos C, Alvarez V, Cava F, Garcia-Lario JV, Hernandez A, Jimenez CV, et al. Update 2012 (www.westgard.com) from the original paper: current databases on biological variation: pros, cons and progress. Scand J Clin Lab Invest 1999;59:491–500. Crossref

About the article

aSantiago Prieto Menchero and María Ángeles Cuadrado Cenzual contributed equally to this article.


Received: 2017-04-24

Accepted: 2017-05-08

Published Online: 2017-06-16

Published in Print: 2017-11-27


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 56, Issue 1, Pages e1–e4, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2017-0354.

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