Consensus Statement for Haemolysed Specimens
Commentary
Consensus Statement for the Management and Reporting of Haemolysed Specimens Tony Badrick1, Harry Barden2, Shaw Callen3, Goce Dimeski4,5, Stephanie Gay1, Peter Graham6, Penny Petinos1, Ken Sikaris7
RCPAQAP, St Leonards, Sydney, NSW, 2065, Australia; 2Pathology Queensland, Hervey Bay Hospital, Hervey Bay, Qld., 4655, Australia; 3Clinpath Laboratories, Kent Town, Adelaide, SA, 5067, Australia; 4Pathology Queensland, Chemical Pathology, Princess Alexandra Hospital, Woolloongabba, Qld., 4102, Australia; 5School of Medicine, University of Queensland, Qld., 4072, Australia; 6AACB, Alexandria, Sydney, NSW, 2015, Australia; 7Melbourne Pathology, Sonic Healthcare, Collingwood, Vic., 3066, Australia. *For correspondence: [email protected] 1
Introduction Haemolysis of blood samples has been documented as the most frequent pre-analytical artefact encountered by laboratories.1 Haemolysis of blood samples can cause interference in testing and result in erroneous results.2,3 The impact of Haemolysis on laboratory test results can be positive or negative depending on the analyser/method. The interference can be the result of various mechanisms including: • Additive - as result of greater concentrations of analytes in cells than in plasma (e.g. potassium, phosphate, folate, lactate dehydrogenase) • Spectral (haemoglobin absorbs at 415, 540 and 570 nm) - leading to interference with alkaline phosphatase, gamma-glutamyl transferase, total and direct bilirubin • Chemical (cross-reactivity) - e.g. errors in creatine kinase due to red cell adenylate kinase • Enzymatic - release of enzymes which degrade analytes (e.g. insulin)4 • Dilutional (gross haemolysis releasing cell fluid and content) - leading to false lowering of results e.g. sodium, chloride etc. The interference with immunoassays is less frequent than with photometric assays, but is still a significant consideration; one of the most commonly affected immunoassays are the cardiac Troponin assays.5 The mechanism of interference with immunoassays is unknown but may be due to released compounds from the lysed cells which then cross-react with antibodies, bind to analyte and inhibit the antibody binding site, or suppress the reactions used in the detection method employed.
A 2014 survey of Australian Laboratories enrolled in the RCPA Quality Assurance Programs confirmed an ongoing variation in the management and reporting of haemolysed samples.6 While there are approved Clinical and Laboratory Standards Institute (CLSI) guidelines to assist laboratories in the evaluation of common interferences in relation to sample integrity,7 to date there are no nationally agreed reporting standards for haemolysed specimens. This consensus statement is primarily intended as a guideline for diagnostic pathology laboratories undertaking any analyses performed on serum or plasma samples. However, these guidelines may also be considered for other sample types e.g. fluids and whole blood samples for point-of-care devices. Guidelines The following guidelines have been endorsed by the Australasian Association of Clinical Biochemists (AACB) and the Royal College of Pathologists of Australasia (RCPA). In this document ‘S’ refers to a standard and ‘C’ refers to a commentary. 1. Best Practice Collection Technique S1.1 Laboratories must ensure correct collection techniques are employed to minimise the incidence of haemolysis resulting from collection and transfer artefact. Laboratories must be familiar with best practice collection processes.
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C1.1 There are a number of resources provided by industry groups and collection tube manufacturers including • CLSI approved standards and guidelines including CLSI document numbers GP41-A6,8 GP39-A6,9 GP43-A4,10 GP44-A4,11 H21-A5,12 H56-A13 • WHO Guidelines on Drawing Blood: Best Practices in Phlebotomy14 • NPAAC Guidelines for Approved Pathology Collection Centres (Requirements for medical pathology specimen collection)15 • Best Practice Pathology Collection (Quality Use of Pathology Program Publication, Department of Health)16 • Factors Affecting Haemolysis, specimencare.com17. This is a useful website featuring a variety of preanalytical issues with blood collection, sponsored by Becton Dickinson S1.2 Education, training and competency must be provided, assessed and recorded for all staff involved in collection of blood samples and other body fluids if relevant. S1.3 Laboratories must ensure documented phlebotomy procedures reflecting best practice are available. C1.2 These should include examples of unacceptable techniques. The most frequently encountered causes of haemolysis of blood samples include use of inappropriately small gauge needles during phlebotomy and transfer of blood from a syringe into a vacutainer tube via a needle (e.g. collected via an intravenous cannula at the time of insertion)18 S1.4. Laboratories must monitor the frequency of haemolysed blood samples and investigate the source of collection to enable continuous improvement. C1.3 Laboratories are advised to target recurrent sources of haemolysed specimens which may include hospital emergency departments, hospital clinical staff, GPs, regional collections or laboratory phlebotomy staff with a view to adapting best practice collection techniques via education, training and competency review. 2. Quantitative Estimation of Haemolysis S2.1 A quantitative estimation of the degree of haemolysis present in serum or plasma samples must be utilised within the laboratory for tests that may be significantly affected by haemolysis. S2.2 A quantitative Haemolysis Index (H-Index) must be used for this purpose, when available, in accordance with 140 Clin Biochem Rev 37 (4) 2016
instrument manufacturers’ recommendations. S2.3 Where a H-Index is not available a visual assessment of haemolysis must be made using a colour chart. C2.1 Colour charts should be traceable to a validated chemistry analyser haemolysis index study such as that provided in the Appendix. C2.2 Visual assessment of haemolysis by comparison with a colour chart is recognised as significantly less accurate than a measured haemolysis index, only gross classification is possible. Colour charts must list at least 4 levels of haemolysis ranging from 1+ to 4+ and each level must list the “equivalent” haemolysis index range. C2.3 Selected levels should reflect points at which assays show clinically significant errors (see Section 3 for guidance on clinical significance) C2.4 If no chemistry analyser H-Index is available for creation of the colour chart, laboratories should use a colour chart from a reliable source such as Table 1 from CLSI document C56-A2 or Appendix. S2.4 Units of measurement for the H-Index are required and must be documented. Where semi-quantitative estimates are in use, their equivalence to a conventional unit (e.g. mg/dL) must be documented. The Appendix shows an example of the equivalence of semi-quantitative estimates to mg/dL on 6 different analytical platforms. C2.5 The H-index should be retained in laboratory databases for each patient episode. C2.6 Where laboratories employ a H-Index other than that provided by instrument manufacturers’ recommendations, adequate validation data must be available. C2.7 Caution must be used if issuing the H-index to requesting clinicians, with consideration to: • Non standardisation of units • Methodological differences • Lack of understanding of the meaning of the value amongst clinical staff 3. Impact of Haemolysis on Test Results S3.1 All laboratories must assess which tests are affected by haemolysis. C3.1 This can be done via in-house or local studies (including data mining)2, manufacturer information or peer reviewed publications.
Consensus Statement for Haemolysed Specimens
S3.2 Laboratories must be aware of, and document, the impact of elevated H-Index levels on significantly affected analyses. C3.2 The effects of haemolysis are method specific depending on wavelengths used or assay components. The H-index at which a clinically relevant effect is seen must be determined for each method in use. Clinically relevant limits can be sourced from: • Published clinical outcome studies describing performance requirements for the specific analyte. • Biological Variation Database derived limits. • RCPA AACB Quality Assurance Programs Allowable Limits of Performance. • Local in-house studies • Chemical Pathologist or expert group opinion. C3.3 The laboratory must record their clinically relevant limits in a readily accessible manner. C3.4 IVD Manufacturers may provide their own cut-offs for their assays for use with their proprietary H-Index. If these are not used or not available, then an alternate documented policy (with reference to point “C2.6” above) should be available from the laboratory. C3.5 Methodological differences in how the H-Index is derived and at what thresholds assays are affected are also recognised. Cut-offs at which assays are affected must be reviewed and updated when analytical platforms are changed. Where multiple different analytical platforms are in use, for example across a network of laboratories or in a large central laboratory, laboratories must ensure H-Index thresholds are appropriate for each. 4. Actions in Response to Haemolysis S4.1 Where analyses are determined to have a significant error resulting from haemolysis, as determined in section 3 above: • Laboratories must have a means to identify affected patient results e.g. via LIS or Expert Systems • Laboratories must determine and document at which H-Index level recollection of the sample is appropriate • If a laboratory decides to report affected tests, the H-Index levels used for these purposes must be documented C4.1 If the laboratory has determined not to report the affected result, the patient report should include a statement explaining why the value was not reported.
C4.2 If the laboratory intends to report the affected result, the presence of haemolysis must be clearly notated on the patient report. A clear statement describing the magnitude and direction of the interference must be included. C4.3 The decision to recollect or report an affected test result should be made in the context of the impact on patient care (e.g. in an Emergency Department setting a recollection may delay lifesaving intervention). This decision should be guided by a policy developed in consultation with requesting clinicians. C4.4 Consideration should be given to the possibility of in vivo haemolysis when the sample appears visually haemolysed with (or without) an elevated H-Index on consecutive occasions or the clinical history is suggestive (e.g. post transfusion, on bypass pump, dialysis, ECMO or sepsis). Similarly, brown coloured serum due to methaemalbumin, normal results for potassium or the same result from arterial and venous collections should prompt further investigation (e.g. haptoglobins). C4.5 When haemolysis is present, consideration must be given to tests performed in other areas of the laboratory which may also be affected including coagulation testing. C4.6 Where it is decided to not report test results or to recollect tests, consideration must be given to tests performed in other areas of the laboratory which may also require recollection or modification to reporting. 5. Whole Blood Analyses S5.1 Consideration must be given to haemolysis interference in whole blood analyses C5.1 POCT samples may be whole blood samples in which a visible or measured change resulting from haemolysis is unable to be readily assessed. When a POCT result shows a result (e.g. K+ elevated significantly) that could be affected by haemolysis, is clinically inconsistent, or contains a relevant instrument flag, further investigation such as repeat testing by an alternate method or other assessment of haemolysis must be considered. 6. Future/Ongoing evaluation While the above guidelines are intended to encourage a more consistent approach to the handling and reporting of results which are affected by haemolysis, future/ongoing research and improvement is still required. Areas to consider could include data mining, guidance on how to perform in-house studies and the defining of appropriate action limits.
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Competing Interests: None declared. References 1. Bonini P, Plebani M, Ceriotti F, Rubboli F. Errors in laboratory medicine. Clin Chem 2002;48:691-8. 2. Lippi G, Salvagno GL, Montagnana M, Brocco G, Guidi GC. Influence of hemolysis on routine clinical chemistry testing. Clin Chem Lab Med 2006;44:311-6. 3. Thomas L. Haemolysis as influence and interference factor. eJIFCC vol 13 no 4: http://www.ifcc.org/ifccfiles/ docs/130401002end.pdf (Accessed 6 June 2016). 4. Chevenne D, Letailleur A, Trivin F, Porquet D. Effect of hemolysis on the concentration of insulin in serum determined by RIA and IRMA. Clin Chem 1998;44:3546. 5. Florkowski C, Wallace J, Walmsley T, George P. The effect of hemolysis on current troponin assays confounding preanalytical variable? Clin Chem 2010;56:1195-7. 6. Petinos P, Gay S, Badrick T. Variation in Laboratory Reporting of Haemolysis - a Need for Harmonisation. Clin Biochem Rev 2015;36:133-7. 7. Clinical and Laboratory Standards Institute (CLSI). Haemolysis, Icterus, and Lipemia/Turbidity Indices as Indicators of interference in Clinical Laboratory Analysis: Approved Guideline, First Edition CLSI C56-A. Wayne, PA, USA: CLSI; 2012. 8. Clinical and Laboratory Standards Institute (CLSI). Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture; Approved Standard, Sixth Edition CLSI GP41-A6. Wayne, PA, USA: CLSI; 2007. 9. Clinical and Laboratory Standards Institute (CLSI). Tubes and Additives for Venous and Capillary Blood Specimen Collection; Approved Standard, Sixth Edition CLSI GP39-A6. Wayne, PA, USA: CLSI; 2010. 10. Clinical and Laboratory Standards Institute (CLSI). Procedures for the Collection of Arterial Blood Specimens; Approved Standard, Fourth Edition CLSI GP43-A4. Wayne, PA, USA: CLSI; 2004. 11. Clinical and Laboratory Standards Institute (CLSI). Procedures for the Handling and Processing of Blood Specimens for Common Laboratory Tests; Approved Guideline Fourth Edition. CLSI GP44-A4. Wayne, PA, USA: CLSI; 2010. 12. Clinical and Laboratory Standards Institute (CLSI). Collection, Transport, and Processing of Blood Specimens for Testing Plasma-Based Coagulation Assays and Molecular Hemostasis Assays; Approved Guideline, Fifth Edition CLSI H21-A5. Wayne, PA, USA: CLSI; 2008.
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13. Clinical and Laboratory Standards Institute (CLSI). Body Fluid Analysis for Cellular Composition; Approved Guideline, First Edition CLSI H56-A. Wayne, PA, USA: CLSI; 2006. 14. World Health Organization. WHO Guidelines on Drawing Blood: Best Practices in Phlebotomy; 2010. http://www. who.int/injection_safety/sign/drawing_blood_best/en/ (Accessed 5 June 2016). 15. NPAAC Guidelines for Approved Pathology Collection Centres (Requirements for Medical Pathology Specimen Collection), Third Edition; 2013. http://www.health.gov. au/internet/main/publishing.nsf/Content/health-npaacdocs-apcc.htm (Accessed 5 June 2016). 16. Best Practice Pathology Collection (Quality Use of Pathology Program Publication, Commonwealth of Australia, Department of Health); 2013. http://www. health.gov.au/internet/main/publishing.nsf/Content/E01 78836BF3A78C3CA257EF20018BB97/$File/Best%20 Practice%20Path%20Coll%20Nov%202013.pdf (Accessed 5 June 2016). 17. Factors Affecting Haemolysis. 2012. http://www. specimencare.com/main.aspx?cat=711&id=3031 (Accessed 5 June 2016). 18. Ong ME, Chan YH, Lim CS. Observational study to determine factors associated with blood sample haemolysis in the emergency department. Ann Acad Med Singapore 2008;37:745-8. Appendix Example of a Haemolysis Colour Chart which also shows haemolysis index concentration levels across different analytical platforms (Courtesy Goce Dimeski, Pathology Queensland)
Commentary
Consensus Statement for the Management and Reporting of Haemolysed Specimens Tony Badrick1, Harry Barden2, Shaw Callen3, Goce Dimeski4,5, Stephanie Gay1, Peter Graham6, Penny Petinos1, Ken Sikaris7
RCPAQAP, St Leonards, Sydney, NSW, 2065, Australia; 2Pathology Queensland, Hervey Bay Hospital, Hervey Bay, Qld., 4655, Australia; 3Clinpath Laboratories, Kent Town, Adelaide, SA, 5067, Australia; 4Pathology Queensland, Chemical Pathology, Princess Alexandra Hospital, Woolloongabba, Qld., 4102, Australia; 5School of Medicine, University of Queensland, Qld., 4072, Australia; 6AACB, Alexandria, Sydney, NSW, 2015, Australia; 7Melbourne Pathology, Sonic Healthcare, Collingwood, Vic., 3066, Australia. *For correspondence: [email protected] 1
Introduction Haemolysis of blood samples has been documented as the most frequent pre-analytical artefact encountered by laboratories.1 Haemolysis of blood samples can cause interference in testing and result in erroneous results.2,3 The impact of Haemolysis on laboratory test results can be positive or negative depending on the analyser/method. The interference can be the result of various mechanisms including: • Additive - as result of greater concentrations of analytes in cells than in plasma (e.g. potassium, phosphate, folate, lactate dehydrogenase) • Spectral (haemoglobin absorbs at 415, 540 and 570 nm) - leading to interference with alkaline phosphatase, gamma-glutamyl transferase, total and direct bilirubin • Chemical (cross-reactivity) - e.g. errors in creatine kinase due to red cell adenylate kinase • Enzymatic - release of enzymes which degrade analytes (e.g. insulin)4 • Dilutional (gross haemolysis releasing cell fluid and content) - leading to false lowering of results e.g. sodium, chloride etc. The interference with immunoassays is less frequent than with photometric assays, but is still a significant consideration; one of the most commonly affected immunoassays are the cardiac Troponin assays.5 The mechanism of interference with immunoassays is unknown but may be due to released compounds from the lysed cells which then cross-react with antibodies, bind to analyte and inhibit the antibody binding site, or suppress the reactions used in the detection method employed.
A 2014 survey of Australian Laboratories enrolled in the RCPA Quality Assurance Programs confirmed an ongoing variation in the management and reporting of haemolysed samples.6 While there are approved Clinical and Laboratory Standards Institute (CLSI) guidelines to assist laboratories in the evaluation of common interferences in relation to sample integrity,7 to date there are no nationally agreed reporting standards for haemolysed specimens. This consensus statement is primarily intended as a guideline for diagnostic pathology laboratories undertaking any analyses performed on serum or plasma samples. However, these guidelines may also be considered for other sample types e.g. fluids and whole blood samples for point-of-care devices. Guidelines The following guidelines have been endorsed by the Australasian Association of Clinical Biochemists (AACB) and the Royal College of Pathologists of Australasia (RCPA). In this document ‘S’ refers to a standard and ‘C’ refers to a commentary. 1. Best Practice Collection Technique S1.1 Laboratories must ensure correct collection techniques are employed to minimise the incidence of haemolysis resulting from collection and transfer artefact. Laboratories must be familiar with best practice collection processes.
Clin Biochem Rev 37 (4) 2016 139
Badrick T et al.
C1.1 There are a number of resources provided by industry groups and collection tube manufacturers including • CLSI approved standards and guidelines including CLSI document numbers GP41-A6,8 GP39-A6,9 GP43-A4,10 GP44-A4,11 H21-A5,12 H56-A13 • WHO Guidelines on Drawing Blood: Best Practices in Phlebotomy14 • NPAAC Guidelines for Approved Pathology Collection Centres (Requirements for medical pathology specimen collection)15 • Best Practice Pathology Collection (Quality Use of Pathology Program Publication, Department of Health)16 • Factors Affecting Haemolysis, specimencare.com17. This is a useful website featuring a variety of preanalytical issues with blood collection, sponsored by Becton Dickinson S1.2 Education, training and competency must be provided, assessed and recorded for all staff involved in collection of blood samples and other body fluids if relevant. S1.3 Laboratories must ensure documented phlebotomy procedures reflecting best practice are available. C1.2 These should include examples of unacceptable techniques. The most frequently encountered causes of haemolysis of blood samples include use of inappropriately small gauge needles during phlebotomy and transfer of blood from a syringe into a vacutainer tube via a needle (e.g. collected via an intravenous cannula at the time of insertion)18 S1.4. Laboratories must monitor the frequency of haemolysed blood samples and investigate the source of collection to enable continuous improvement. C1.3 Laboratories are advised to target recurrent sources of haemolysed specimens which may include hospital emergency departments, hospital clinical staff, GPs, regional collections or laboratory phlebotomy staff with a view to adapting best practice collection techniques via education, training and competency review. 2. Quantitative Estimation of Haemolysis S2.1 A quantitative estimation of the degree of haemolysis present in serum or plasma samples must be utilised within the laboratory for tests that may be significantly affected by haemolysis. S2.2 A quantitative Haemolysis Index (H-Index) must be used for this purpose, when available, in accordance with 140 Clin Biochem Rev 37 (4) 2016
instrument manufacturers’ recommendations. S2.3 Where a H-Index is not available a visual assessment of haemolysis must be made using a colour chart. C2.1 Colour charts should be traceable to a validated chemistry analyser haemolysis index study such as that provided in the Appendix. C2.2 Visual assessment of haemolysis by comparison with a colour chart is recognised as significantly less accurate than a measured haemolysis index, only gross classification is possible. Colour charts must list at least 4 levels of haemolysis ranging from 1+ to 4+ and each level must list the “equivalent” haemolysis index range. C2.3 Selected levels should reflect points at which assays show clinically significant errors (see Section 3 for guidance on clinical significance) C2.4 If no chemistry analyser H-Index is available for creation of the colour chart, laboratories should use a colour chart from a reliable source such as Table 1 from CLSI document C56-A2 or Appendix. S2.4 Units of measurement for the H-Index are required and must be documented. Where semi-quantitative estimates are in use, their equivalence to a conventional unit (e.g. mg/dL) must be documented. The Appendix shows an example of the equivalence of semi-quantitative estimates to mg/dL on 6 different analytical platforms. C2.5 The H-index should be retained in laboratory databases for each patient episode. C2.6 Where laboratories employ a H-Index other than that provided by instrument manufacturers’ recommendations, adequate validation data must be available. C2.7 Caution must be used if issuing the H-index to requesting clinicians, with consideration to: • Non standardisation of units • Methodological differences • Lack of understanding of the meaning of the value amongst clinical staff 3. Impact of Haemolysis on Test Results S3.1 All laboratories must assess which tests are affected by haemolysis. C3.1 This can be done via in-house or local studies (including data mining)2, manufacturer information or peer reviewed publications.
Consensus Statement for Haemolysed Specimens
S3.2 Laboratories must be aware of, and document, the impact of elevated H-Index levels on significantly affected analyses. C3.2 The effects of haemolysis are method specific depending on wavelengths used or assay components. The H-index at which a clinically relevant effect is seen must be determined for each method in use. Clinically relevant limits can be sourced from: • Published clinical outcome studies describing performance requirements for the specific analyte. • Biological Variation Database derived limits. • RCPA AACB Quality Assurance Programs Allowable Limits of Performance. • Local in-house studies • Chemical Pathologist or expert group opinion. C3.3 The laboratory must record their clinically relevant limits in a readily accessible manner. C3.4 IVD Manufacturers may provide their own cut-offs for their assays for use with their proprietary H-Index. If these are not used or not available, then an alternate documented policy (with reference to point “C2.6” above) should be available from the laboratory. C3.5 Methodological differences in how the H-Index is derived and at what thresholds assays are affected are also recognised. Cut-offs at which assays are affected must be reviewed and updated when analytical platforms are changed. Where multiple different analytical platforms are in use, for example across a network of laboratories or in a large central laboratory, laboratories must ensure H-Index thresholds are appropriate for each. 4. Actions in Response to Haemolysis S4.1 Where analyses are determined to have a significant error resulting from haemolysis, as determined in section 3 above: • Laboratories must have a means to identify affected patient results e.g. via LIS or Expert Systems • Laboratories must determine and document at which H-Index level recollection of the sample is appropriate • If a laboratory decides to report affected tests, the H-Index levels used for these purposes must be documented C4.1 If the laboratory has determined not to report the affected result, the patient report should include a statement explaining why the value was not reported.
C4.2 If the laboratory intends to report the affected result, the presence of haemolysis must be clearly notated on the patient report. A clear statement describing the magnitude and direction of the interference must be included. C4.3 The decision to recollect or report an affected test result should be made in the context of the impact on patient care (e.g. in an Emergency Department setting a recollection may delay lifesaving intervention). This decision should be guided by a policy developed in consultation with requesting clinicians. C4.4 Consideration should be given to the possibility of in vivo haemolysis when the sample appears visually haemolysed with (or without) an elevated H-Index on consecutive occasions or the clinical history is suggestive (e.g. post transfusion, on bypass pump, dialysis, ECMO or sepsis). Similarly, brown coloured serum due to methaemalbumin, normal results for potassium or the same result from arterial and venous collections should prompt further investigation (e.g. haptoglobins). C4.5 When haemolysis is present, consideration must be given to tests performed in other areas of the laboratory which may also be affected including coagulation testing. C4.6 Where it is decided to not report test results or to recollect tests, consideration must be given to tests performed in other areas of the laboratory which may also require recollection or modification to reporting. 5. Whole Blood Analyses S5.1 Consideration must be given to haemolysis interference in whole blood analyses C5.1 POCT samples may be whole blood samples in which a visible or measured change resulting from haemolysis is unable to be readily assessed. When a POCT result shows a result (e.g. K+ elevated significantly) that could be affected by haemolysis, is clinically inconsistent, or contains a relevant instrument flag, further investigation such as repeat testing by an alternate method or other assessment of haemolysis must be considered. 6. Future/Ongoing evaluation While the above guidelines are intended to encourage a more consistent approach to the handling and reporting of results which are affected by haemolysis, future/ongoing research and improvement is still required. Areas to consider could include data mining, guidance on how to perform in-house studies and the defining of appropriate action limits.
Clin Biochem Rev 37 (4) 2016 141
Badrick T et al.
Competing Interests: None declared. References 1. Bonini P, Plebani M, Ceriotti F, Rubboli F. Errors in laboratory medicine. Clin Chem 2002;48:691-8. 2. Lippi G, Salvagno GL, Montagnana M, Brocco G, Guidi GC. Influence of hemolysis on routine clinical chemistry testing. Clin Chem Lab Med 2006;44:311-6. 3. Thomas L. Haemolysis as influence and interference factor. eJIFCC vol 13 no 4: http://www.ifcc.org/ifccfiles/ docs/130401002end.pdf (Accessed 6 June 2016). 4. Chevenne D, Letailleur A, Trivin F, Porquet D. Effect of hemolysis on the concentration of insulin in serum determined by RIA and IRMA. Clin Chem 1998;44:3546. 5. Florkowski C, Wallace J, Walmsley T, George P. The effect of hemolysis on current troponin assays confounding preanalytical variable? Clin Chem 2010;56:1195-7. 6. Petinos P, Gay S, Badrick T. Variation in Laboratory Reporting of Haemolysis - a Need for Harmonisation. Clin Biochem Rev 2015;36:133-7. 7. Clinical and Laboratory Standards Institute (CLSI). Haemolysis, Icterus, and Lipemia/Turbidity Indices as Indicators of interference in Clinical Laboratory Analysis: Approved Guideline, First Edition CLSI C56-A. Wayne, PA, USA: CLSI; 2012. 8. Clinical and Laboratory Standards Institute (CLSI). Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture; Approved Standard, Sixth Edition CLSI GP41-A6. Wayne, PA, USA: CLSI; 2007. 9. Clinical and Laboratory Standards Institute (CLSI). Tubes and Additives for Venous and Capillary Blood Specimen Collection; Approved Standard, Sixth Edition CLSI GP39-A6. Wayne, PA, USA: CLSI; 2010. 10. Clinical and Laboratory Standards Institute (CLSI). Procedures for the Collection of Arterial Blood Specimens; Approved Standard, Fourth Edition CLSI GP43-A4. Wayne, PA, USA: CLSI; 2004. 11. Clinical and Laboratory Standards Institute (CLSI). Procedures for the Handling and Processing of Blood Specimens for Common Laboratory Tests; Approved Guideline Fourth Edition. CLSI GP44-A4. Wayne, PA, USA: CLSI; 2010. 12. Clinical and Laboratory Standards Institute (CLSI). Collection, Transport, and Processing of Blood Specimens for Testing Plasma-Based Coagulation Assays and Molecular Hemostasis Assays; Approved Guideline, Fifth Edition CLSI H21-A5. Wayne, PA, USA: CLSI; 2008.
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13. Clinical and Laboratory Standards Institute (CLSI). Body Fluid Analysis for Cellular Composition; Approved Guideline, First Edition CLSI H56-A. Wayne, PA, USA: CLSI; 2006. 14. World Health Organization. WHO Guidelines on Drawing Blood: Best Practices in Phlebotomy; 2010. http://www. who.int/injection_safety/sign/drawing_blood_best/en/ (Accessed 5 June 2016). 15. NPAAC Guidelines for Approved Pathology Collection Centres (Requirements for Medical Pathology Specimen Collection), Third Edition; 2013. http://www.health.gov. au/internet/main/publishing.nsf/Content/health-npaacdocs-apcc.htm (Accessed 5 June 2016). 16. Best Practice Pathology Collection (Quality Use of Pathology Program Publication, Commonwealth of Australia, Department of Health); 2013. http://www. health.gov.au/internet/main/publishing.nsf/Content/E01 78836BF3A78C3CA257EF20018BB97/$File/Best%20 Practice%20Path%20Coll%20Nov%202013.pdf (Accessed 5 June 2016). 17. Factors Affecting Haemolysis. 2012. http://www. specimencare.com/main.aspx?cat=711&id=3031 (Accessed 5 June 2016). 18. Ong ME, Chan YH, Lim CS. Observational study to determine factors associated with blood sample haemolysis in the emergency department. Ann Acad Med Singapore 2008;37:745-8. Appendix Example of a Haemolysis Colour Chart which also shows haemolysis index concentration levels across different analytical platforms (Courtesy Goce Dimeski, Pathology Queensland)
