Managing hemolyzed samples in clinical laboratories

Critical Reviews in Clinical Laboratory Sciences

Volumn 57, Issue 1, 2020, Pages 1-21

  Simundic, Ana Maria ^a   Baird, Geoffrey ^b   Cadamuro, Janne ^c   Costelloe, Seán J ^d   Lippi, Giuseppe ^e  

^a University Hospital Sveti Duh   (Croatia)

^b UNIVERSITY OF WASHINGTON   (United States)

^c PARACELSUS MEDICAL UNIVERSITY   (Austria)

^d Department of Medicine National University of Ireland Cork   (Ireland)

^e UNIVERSITY OF VERONA   (Italy)

Author keywords

Hemolysis; interference; preanalytical phase; standardization

Indexed keywords

BLOOD SAMPLING; CELL COMPONENT; CLINICAL LABORATORY; HEALTH CARE COST; HEMATOLOGY; HEMOLYSIS; HUMAN; IMMUNOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; LABORATORY PERSONNEL; LABORATORY TEST; PHLEBOTOMY; PREVALENCE; PRIORITY JOURNAL; QUALITY CONTROL; REVIEW; SPECTROPHOTOMETRY; STANDARDIZATION; TOTAL QUALITY MANAGEMENT; VISION; BLOOD ANALYSIS; CLINICAL LABORATORY SERVICE; LABORATORY AUTOMATION;

AUTOMATION, LABORATORY; BLOOD CHEMICAL ANALYSIS; BLOOD SPECIMEN COLLECTION; CLINICAL LABORATORY SERVICES; HEMOLYSIS; HUMANS;

EID: 85074456003     PISSN: 10408363     EISSN: 1549781X     Source Type: Journal    
DOI: 10.1080/10408363.2019.1664391     Document Type: Review

References (107)

1. Guder WG. Haemolysis as an influence and interference factor in clinical chemistry. J Clin Chem Clin Biochem. 1986;24(2):125–126.
2. Simundic AM, Topic E, Nikolac N. Hemolysis detection and management of hemolyzed specimens. Biochem Med. 2010;20:154–159.
3. Jones BA, Calam RR, Howanitz PJ. Chemistry specimen acceptability: a College of American Pathologists Q-Probes study of 453 laboratories. Arch Pathol Lab Med. 1997;121(1):19–26.
4. Simundic AM, Nikolac N, Vukasovic I, et al. The prevalence of preanalytical errors in a Croatian ISO 15189 accredited laboratory. Clin Chem Lab Med. 2010;48(7):1009–1014.
5. Carraro P, Servidio G, Plebani M. Hemolyzed specimens: a reason for rejection or a clinical challenge? Clin Chem. 2000;46(2):306–307.
6. Simundic AM, Nikolac N, Guder WG. Preanalytical variation and preexamination processes In Rifai N, Horvath R, Wittwer C, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 6th ed. St. Louis, Missour: Elsevier; 2018. p. 81–120.
7. Guillaud C, Loustau V, Michel M. Hemolytic anemia in adults: main causes and diagnostic procedures. Expert Rev Hematol. 2012;5(2):229–241.
8. Barcellini W, Fattizzo B. Clinical applications of hemolytic markers in the differential diagnosis and management of hemolytic anemia. Dis Markers. 2015;2015:635670.
9. Langlois MR, Delanghe JR. Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem. 1996;42(10):1589–1600.
10. Lippi G, Blanckaert N, Bonini P, et al. Hemolysis: an overview of the leading cause of unsuitable specimens in clinical laboratories. Clin Chem Lab Med. 2008;46(6):764–772.
11. Lippi G, Mercadanti M, Aloe R, et al. Erythrocyte mechanical fragility is increased in patients with type 2 diabetes. Eur J Intern Med. 2012;23(2):150–153.
12. Thomas MR, Scully M. Microangiopathy in cancer: causes, consequences, and management. Cancer Treat Res. 2019;179:151–158.
13. Schauf CL, Frischer H, Davis FA. Mechanical fragility of erythrocytes in multiple sclerosis. Neurology. 1980;30(3):323–325.
14. Raval JS, Waters JH, Seltsam A, et al. Menopausal status affects the susceptibility of stored RBCs to mechanical stress. Vox Sang. 2011;100(4):418–4121.
15. Maurin C, Vassal O, Darien M, et al. Immune hemolysis secondary to injection of contrast medium. Transfusion. 2018;58(9):2113–2114.
16. Burns ER, Yoshikawa N. Hemolysis in serum samples drawn by emergency department personnel versus laboratory phlebotomists. Lab Med. 2002;33(5):378–380.
17. Kennedy C, Angermuller S, King R, et al. A comparison of hemolysis rates using intravenous catheters versus venipuncture tubes for obtaining blood samples. J Emerg Nurs. 1996;22(6):566–569.
18. Tanabe P, Kyriacou DN, Garland F, et al. Factors affecting the risk of blood bank specimen hemolysis. Acad Emerg Med. 2003;10(8):897–900.
19. Lippi G, Salvagno GL, Montagnana M, et al. Influence of the needle bore size used for collecting venous blood samples on routine clinical chemistry testing. Clin Chem Lab Med. 2006;44(8):1009–1014.
20. Sharp MK, Mohammad SF. Scaling of hemolysis in needles and catheters. Ann Biomed Eng. 1998; 26(5):788–797.
21. Mrazek C, Simundic AM, Wiedemann H, et al. The relationship between vacuum and hemolysis during catheter blood collection: a retrospective analysis of six large cohorts. Clin Chem Lab Med. 2017;55(8):1129–1134.
22. Simundic AM, Bölenius K, Cadamuro J, et al. Joint EFLM-COLABIOCLI Recommendation for venous blood sampling. Clin Chem Lab Med. 2018;56(12):2015–2038.
23. Juricic G, Kopcinovic LM, Saracevic A, et al. Liquid citrate acidification introduces significant glucose bias and leads to misclassification of patients with diabetes. Clin Chem Lab Med. 2016;54(2):363–371.
24. Ernst DJ. Flawless phlebotomy: becoming a great collector. Nursing. 1995;25(10):54–57.
25. Grant MS. The effect of blood drawing techniques and equipment on the hemolysis of ED laboratory blood samples. J Emerg Nurs. 2003;29(2):116–121.
26. Baer DM, Ernst DJ, Willeford SI, et al. Investigating elevated potassium values. MLO Med Lab Obs. 2006;38(11):24, 26, 30–31.
27. Statland BE, Bokelund H, Winkel P. Factors contributing to intra-individual variation of serum constituents: 4. Effects of posture and tourniquet application on variation of serum constituents in healthy subjects. Clin Chem. 1974;20(12):1513–1519.
28. Shah KG, Idrovo JP, Nicastro J, et al. A retrospective analysis of the incidence of hemolysis in type and screen specimens from trauma patients. Int J Angiol. 2009;18(04):182–183.
29. Söderberg J, Jonsson PA, Wallin O, et al. Haemolysis index-an estimate of preanalytical quality in primary health care. Clin Chem Lab Med. 2009;47(8):940–944.
30. Simundic AM, Church S, Cornes MP, et al. Compliance of blood sampling procedures with the CLSI H3-A6 guidelines: An observational study by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) working group for the preanalytical phase (WG-PRE.). Clin Chem Lab Med. 2015;53(9):1321–1331.
31. Simundic AM, Cornes M, Grankvist K, et al. Survey of national guidelines, education and training on phlebotomy in 28 European countries: an original report by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) working group for the preanalytical phase (WG-PA). Clin Chem Lab Med. 2013;51(8):1585–1593.
32. Simundic AM. Who is doing Phlebotomy in Europe? In Guder WG, Narayanan S, eds. Pre-Examination Procedures in Laboratory Diagnostics. Preanalytical Aspects and their Impact on the Quality of Medical Laboratory Results. Berlin: De Gruyter; 2015. p. 90–94.
33. Cadamuro J, von Meyer A, Wiedemann H, et al. Hemolysis rates in blood samples: differences between blood collected by clinicians and nurses and the effect of phlebotomy training. Clin Chem Lab Med. 2016;54(12):1987–1992.
34. Simundic AM, Lippi G. Preanalytical phase–a continuous challenge for laboratory professionals. Biochem Med. 2012;22(2):145–149.
35. Lippi G, Avanzini P, Pavesi F, et al. Studies on in vitro hemolysis and utility of corrective formulas for reporting results on hemolyzed specimens. Biochem Med. 2011;21(3):297–305.
36. Kirschbaumweg LT. Hemolysis as influence & interference factor. EJIFCC. 2002;13(4):95–98.
37. Becan-McBride K. Laboratory sampling. Does the process affect the outcome? J Intraven Nurs. 1999;22(3):137–142.
38. Sodi R, Darn SM, Stott A. Pneumatic tube system induced haemolysis: assessing sample type susceptibility to haemolysis. Ann Clin Biochem. 2004;41(Pt 3):237–240.
39. Cadamuro J, Mrazek C, Leichtle AB, et al. Influence of centrifugation conditions on the results of 77 routine clinical chemistry analytes using standard vacuum blood collection tubes and the new BD-Barricor tubes. Biochem Med. 2018;28(1):010704.
40. Munnix I, Schellart M, Gorissen C, et al. Factors reducing hemolysis rates in blood samples from the emergency department. Clin Chem Lab Med. 2011;49(1):157–158.
41. Heireman L, Van Geel P, Musger L, et al. Causes, consequences and management of sample hemolysis in the clinical laboratory. Clin Biochem. 2017;50(18):1317–1322.
42. Joshi S, Vaitkute R, Jeffery J, et al. Haemolysis in neonatal blood samples: a survey of practice. Ann Clin Biochem. 2007;44(Pt 2):178–181.
43. Makarem A. Hemoglobins, myoglobins, and haptoglobins In: Henry RJ, Cannon DC, Winkelman JW, eds. Clinical chemistry: principles and techniques. Hagerstown, MD: Harper & Row, 1966. 1125–1127.
44. Pai SH, Cyr-Manthey M. Effects of hemolysis on chemistry tests. Lab Med. 1991;22(6):408–410.
45. Koseoglu M, Hur A, Atay A, et al. Effects of hemolysis interferences on routine biochemistry parameters. Biochem Med. 2011;21(1):79–85.
46. Szasz G, Gerhardt W, Gruber W, et al. Creatine kinase in serum: 2. Interference of adenylate kinase with the assay. Clin Chem. 1976;22(11):1806–1811.
47. Sonntag O. Hemolysis as an interference factor in clinical chemistry. J Clin Chem Clin Biochem. 1986;24(2):127–139.
48. van der Woerd-de Lange JA, Guder WG, Schleicher E, et al. Studies on the interference by haemoglobin in the determination of bilirubin. J Clin Chem Clin Biochem. 1983;21(7):437–443.
49. Wenk RE. Mechanism of interference by hemolysis in immunoassays and requirements for sample quality. Clin Chem. 1998;44(12):2554.
50. Fernandez P, Llopis MA, Perich C, et al. Harmonization in hemolysis detection and prevention. A working group of the Catalonian Health Institute (ICS) experience. Clin Chem Lab Med. 2014;52(11):1557–1568.
51. EQAnord. Nordic Hemolysis project. Effects of hemoglobin on some common serum analysis. [cited 2019 May 02]. Available from: http://deks.dk/pr/Nordic_Hemolysis_project_2014.pdf
52. Hawkins R. Variability in potassium/hemoglobin ratios for hemolysis correction. Clin Chem. 2002;48(5):796.
53. Lippi G, Fontana R, Avanzini P, et al. Influence of spurious hemolysis on blood gas analysis. Clin Chem Lab Med. 2013;51(8):1651–1654.
54. Baird G. Preanalytical considerations in blood gas analysis. Biochem Med. 2013;23(1):19–27.
55. Cook PR, Glenn C, Armston A. Effect of hemolysis on insulin determination by the Beckman Coulter Unicell DXI 800 immunoassay analyzer. Clin Biochem. 2010;43(6):621–622.
56. Woolley A, Golmard JL, Kitchen S. Effects of haemolysis, icterus and lipaemia on coagulation tests as performed on Stago STA-Compact-Max analyser. Int J Lab Hematol. 2016;38(4):375–388.
57. D'Angelo G, Villa C, Tamborini A, et al. Evaluation of the main coagulation tests in the presence of hemolysis in healthy subjects and patients on oral anticoagulant therapy. Int Jnl Lab Hem. 2015;37(6):819–833.
58. Novelli C, Vidali M, Brando B, et al. A collaborative study by the Working Group on Hemostasis and Thrombosis of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC) on the interference of haemolysis on five routine blood coagulation tests by evaluation of 269 paired haemolysed/non-haemolysed samples. Biochem Med. 2018;28(3):030711.
59. Chandler WL, Ferrell C, Trimble S, et al. Development of a rapid emergency hemorrhage panel. Transfusion. 2010;50(12):2547–2552.
60. Ranjitkar P, Greene DN, Baird GS, et al. Establishing evidence-based thresholds and laboratory practices to reduce inappropriate treatment of pseudohyperkalemia. Clin Biochem. 2017;50(12):663–669.
61. Green SF. The cost of poor blood specimen quality and errors in preanalytical processes. Clin Biochem. 2013;46(13-14):1175–1179.
62. Bodansky DMS, Lumley SE, Chakraborty R, et al. Potential cost savings by minimisation of blood sample delays on care decision making in urgent care services. Ann Med Surg. 2017;20:37–40.
63. Jacobs P, Costello J, Beckles M. Cost of haemolysis. Ann Clin Biochem. 2012;49(Pt 4):412.
64. Lippi G, Bonelli P, Cervellin G. Prevalence and cost of hemolyzed samples in a large urban emergency department. Int Jnl Lab Hem. 2014;36(1):e24–6.
65. Cadamuro J, Wiedemann H, Mrazek C, et al. The economic burden of hemolysis. Clin Chem Lab Med. 2015;53(11):e285–8.
66. Cadamuro J, Fiedler GM, Mrazek C, et al. In-vitro hemolysis and its financial impact using different blood collection systems. J Lab Med. 2016;40:49–55.
67. Lippi G, Giavarina D, Gelati M, et al. Reference range of hemolysis index in serum and lithium-heparin plasma measured with two analytical platforms in a population of unselected outpatients. Clin Chim Acta. 2014;429:143–146.
68. Glick MR, Ryder KW, Glick SJ, et al. Unreliable visual estimation of the incidence and amount of turbidity, hemolysis, and icterus in serum from hospitalized patients. Clin Chem. 1989;35(5):837–839.
69. Simundic AM, Nikolac N, Ivankovic V, et al. Comparison of visual vs. automated detection of lipemic, icteric and hemolyzed specimens: can we rely on a human eye? Clin Chem Lab Med. 2009;47(11):1361–1365.
70. Shah JS, Soon PS, Marsh DJ. Comparison of methodologies to detect low levels of hemolysis in serum for accurate assessment of serum microRNAs. PLoS ONE. 2016;11(4):e0153200.
71. Luksic AH, Nikolac Gabaj N, Miler M, et al. Visual assessment of hemolysis affects patient safety. Clin Chem Lab Med. 2018;56(4):574–581.
72. Lippi G, Cadamuro J. Visual assessment of sample quality: quo usque tandem? Clin Chem Lab Med. 2018;56(4):513–515.
73. Farrell CJ, Carter AC. Serum indices: managing assay interference. Ann Clin Biochem. 2016;53(Pt 5):527–538.
74. Lippi G, Luca Salvagno G, Blanckaert N, et al. Multicenter evaluation of the hemolysis index in automated clinical chemistry systems. Clin Chem Lab Med. 2009;47(8):934–939.
75. Nikolac Gabaj N, Miler M, Vrtarić A, et al. Precision, accuracy, cross reactivity and comparability of serum indices measurement on Abbott Architect c8000, Beckman Coulter AU5800 and Roche Cobas 6000 c501 clinical chemistry analyzers. Clin Chem Lab Med. 2018;56(5):776–788.
76. Lippi G, Avanzini P, Campioli D, et al. Systematical assessment of serum indices does not impair efficiency of clinical chemistry testing: a multicenter study. Clin Biochem. 2013;46(13-14):1281–1284.
77. von Meyer A, Cadamuro J, Lippi G, et al. Call for more transparency in manufacturers declarations on serum indices: On behalf of the Working Group for Preanalytical Phase (WG-PRE), European Federation of Clinical Chemistry and Laboratory Medicine (EFLM). Clin Chim Acta. 2018;484:328–332.
78. Lippi G, Favaloro EJ, Franchini M. Hemolysis index for the screening of intravascular hemolysis: a novel diagnostic opportunity? Blood Transfus. 2018;16(5):433–437.
79. Sciacovelli L, Secchiero S, Zardo L, et al. Risk management in laboratory medicine: quality assurance programs and professional competence. Clin Chem Lab Med. 2007;45(6):756–765.
80. CLSI. Hemolysis, Icterus, and Lipemia/Turbidity Indices as Indicators of Interference in Clinical. Laboratory Analysis - Approved Guideline. CLSI document C56-A. Wayne (PA): Clinical and Laboratory Standards Institute; 2012.
81. Yoon J, Thapa S, Chow RD, et al. Hemolysis as a rare but potentially life-threatening complication of hemodialysis: a case report. BMC Res Notes. 2014;7:475.
82. Topic E, Nikolac N, Panteghini M, et al. How to assess the quality of your analytical method? Clin Chem Lab Med. 2015;53(11):1707–1718.
83. Lippi G, Lima-Oliveira G, Brocco G, et al. Estimating the intra- and inter-individual imprecision of manual pipetting. Clin Chem Lab Med. 2017;55(7):962–966.
84. Miller WG, Erek A, Cunningham TD, et al. Commutability limitations influence quality control results with different reagent lots. Clin Chem. 2011;57(1):76–83.
85. Fraser CG, Peake MJ, Cresswell MA. Problems associated with clinical chemistry quality control materials. CRC Crit Rev Clin Lab Sci. 1980;12(1):59–86.
86. Lippi G, Cadamuro J, von Meyer A, et al. Local quality assurance of serum or plasma (HIL) indices. Clin Biochem. 2018;54:112–118.
87. Lippi G, Cadamuro J, Danese E, et al. Internal quality assurance of HIL indices on Roche Cobas c702. PLoS ONE. 2018;13(7):e0200088
88. Kristensen GB, Aakre KM, Kristoffersen AH, et al. How to conduct external quality assessment schemes for the pre-analytical phase? Biochem Med. 2014;24:114–122.
89. Nikolac N, Krleza JL, Simundic AM. Preanalytical external quality assessment of the Croatian Society of Medical Biochemistry and Laboratory Medicine and CROQALM: finding undetected weak spots. Biochem Med. 2017;27:131–143.
90. Sciacovelli L, Panteghini M, Lippi G, et al. Defining a roadmap for harmonizing quality indicators in Laboratory Medicine: a consensus statement on behalf of the IFCC Working Group "Laboratory Error and Patient Safety" and EFLM Task and Finish Group "Performance specifications for the extra-analytical phases. Clin Chem Lab Med. 2017;55:1478–1488.
91. Cadamuro J. Internal quality assurance for preanalytical phase In: Guder WG, Narayanan S, eds. Pre-examination Procedures in Laboratory Diagnostics. Berlin: de Gruyter, 2015. 345–351.
92. Cadamuro J, Gaksch M, Mrazek C, et al. How do we use the data from pre-analytical quality indicators and how should we? J Lab Precis Med. 2018;3:1–9.
93. Lippi G, Sciacovelli L, Simundic AM, et al. Innovative software for recording preanalytical errors in accord with the IFCC quality indicators. Clin Chem Lab Med. 2017;55(3):e51–3.
94. CLSI. Interference Testing in Clinical Chemistry - Third Edition. CLSI document EP-07. Wayne (PA): Clinical and Laboratory Standards Institute; 2018.
95. Delgado JA, Morell-Garcia D, Bauça JM. Hemolysis interference studies: the particular case of sodium ion. EJIFCC. 2019;30(1):25–34.
96. Lippi G. Interference studies: focus on blood cell lysates preparation and testing. Clin Lab. 2012;58(3-4):351–355.
97. Lippi G, Pavesi F, Benegiamo A, et al. What do hemolyzed whole-blood specimens look like? Analysis with a CellaVision DM96 automated image analysis system. J Lab Autom. 2015;20(1):60–63.
98. Srivastava T, Negandhi H, Neogi SB, et al. Methods for hemoglobin estimation: a review of “what works. J Hematol Transfus. 2014;2:1028.
99. Lippi G, Montagnana M, Salvagno GL, et al. Interference of blood cell lysis on routine coagulation testing. Arch Pathol Lab Med. 2006;130(2):181–184.
100. Simundic AM, Bilic-Zulle L, Nikolac N, et al. The quality of the extra-analytical phase of laboratory practice in some developing European countries and Mexico - a multicentric study. Clin Chem Lab Med. 2011;49(2):215–228.
101. Bilić Zulle L, Simundic AM, Supak Smolcic V, et al. Self reported routines and procedures for the extra-analytical phase of laboratory practice in Croatia - cross-sectional survey study. Biochem Med. 2010;20(1):64–74.
102. Cadamuro J, Lippi G, von Meyer A, et al. European survey on preanalytical sample handling - Part 2: Practices of European laboratories on monitoring and processing hemolytic, icteric and lipemic samples. On behalf of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase (WG-PRE). Biochem med. 2019;29(2):020705.
103. Pineda-Tenor D, Prada de Medio EB, Torres PM, et al. 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). Clin Chem Lab Med. 2017;56(1):e1–e4.
104. Lippi G, Banfi G, Buttarello M, et al. Recommendations for detection and management of unsuitable samples in clinical laboratories. Clin Chem Lab Med. 2007;45(6):728–736.
105. Lippi G, Cadamuro J, von Meyer A, et al. European Federation of Clinical Chemistry and Laboratory Medicine Working Group for Preanalytical Phase. Practical recommendations for managing hemolyzed samples in clinical chemistry testing. Clin Chem Lab Med. 2018;56(5):718–727.
106. Fraser CG. Reference change values. Clin Chem Lab Med. 2011;50(5):807–812.
107. Szoke D, Caruso S, Pasqualetti S, et al. Suppressing all test results in grossly hemolyzed samples: Is this approach appropriate in every case? Clin Chem Lab Med. 2019;57(6):e118–e120.