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Licensed Unlicensed Requires Authentication Published by De Gruyter August 5, 2019

Heparin and citrate additive carryover during blood collection

Martin H. Keppel, Simon Auer, Giuseppe Lippi, Alexander von Meyer, Michael Cornes, Thomas K. Felder, Hannes Oberkofler, Cornelia Mrazek, Elisabeth Haschke-Becher and Janne Cadamuro ORCID logo

Abstract

Background

Published evidence on the risk of additive carryover during phlebotomy remains elusive. We aimed to assess potential carryover of citrated and heparinized blood and the relative volume needed to bias clinical chemistry and coagulation tests.

Methods

We simulated standardized phlebotomies to quantify the risk of carryover of citrate and heparin additives in distilled water, using sodium and lithium as surrogates. We also investigated the effects of contamination of heparinized blood samples with increasing volumes of citrated blood and pure citrate on measurements of sodium, potassium, chloride, magnesium, total and ionized calcium and phosphate. Likewise, we studied the effects of contamination of citrated blood samples with increasing volumes of heparinized blood on heparin (anti-Xa) activity, lithium, activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). We interpreted these results based on measurement deviations beyond analytical, biological and clinical significance.

Results

Standardized phlebotomy simulations revealed no significant differences in concentration of surrogate markers. Clinically significant alterations were observed after contamination of heparinized blood samples with volumes of citrated blood beyond 5–50 μL for ionized calcium and beyond 100–1000 μL for sodium, chloride and total calcium. Investigations of pure citrate carryover revealed similar results at somewhat lower volumes. Heparinized blood carryover showed clinically significant interference of coagulation testing at volumes beyond 5–100 μL.

Conclusions

Our results suggest that during a standardized phlebotomy, heparin or citrate contamination is highly unlikely. However, smaller volumes are sufficient to severely alter test results when deviating from phlebotomy guidelines.


Corresponding author: Janne Cadamuro, MD, University Hospital Salzburg, Paracelsus Medical University, Department of Laboratory Medicine, Salzburger Landeskliniken, Müllner Hauptstr. 48, 5020 Salzburg, Austria, Phone: 0043-57255-57263, Fax: 0043-57255-23199

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

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. 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.

References

1. Rohr UP, Binder C, Dieterle T, Giusti F, Messina CG, Toerien E, et al. The value of in vitro diagnostic testing in medical practice: a status report. PLoS One 2016;11:e0149856.10.1371/journal.pone.0149856Search in Google Scholar PubMed PubMed Central

2. Plebani M, Laposata M, Lundberg GD. The brain-to-brain loop concept for laboratory testing 40 years after its introduction. Am J Clin Pathol 2011;136:829–33.10.1309/AJCPR28HWHSSDNONSearch in Google Scholar PubMed

3. Jafri L, Khan AH, Ghani F, Shakeel S, Raheem A, Siddiqui I. Error identification in a high-volume clinical chemistry laboratory: five-year experience. Scand J Clin Lab Invest 2015;75:296–300.10.3109/00365513.2015.1010175Search in Google Scholar PubMed

4. Cadamuro J. Internal quality assurance for preanalytical phase. In: Guder WG, Narayanan S, editors. Pre-examination procedures in laboratory diagnostics. Berlin: De Gruyter, 2015:345–51.10.1515/9783110334043-040Search in Google Scholar

5. Calam RR, Cooper MH. Recommended “order of draw” for collecting blood specimens into additive-containing tubes. Clin Chem 1982;28:1399.10.1093/clinchem/28.6.1399Search in Google Scholar

6. Cornes M, van Dongen-Lases E, Grankvist K, Ibarz M, Kristensen G, Lippi G, et al. Order of blood draw: Opinion Paper by the European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase (WG-PRE). Clin Chem Lab Med 2017;55:27–31.10.1515/cclm-2016-0426Search in Google Scholar PubMed

7. Simundic AM, Bolenius K, Cadamuro J, Church S, Cornes MP, van Dongen-Lases EC, et al. Joint EFLM-COLABIOCLI recommendation for venous blood sampling. Clin Chem Lab Med 2018;56:2015–38.10.1515/cclm-2018-0602Search in Google Scholar PubMed

8. Sharratt CL, Gilbert CJ, Cornes MC, Ford C, Gama R. EDTA sample contamination is common and often undetected, putting patients at unnecessary risk of harm. Int J Clin Pract 2009;63:1259–62.10.1111/j.1742-1241.2008.01981.xSearch in Google Scholar PubMed

9. Sulaiman RA, Cornes MP, Whitehead SJ, Othonos N, Ford C, Gama R. Effect of order of draw of blood samples during phlebotomy on routine biochemistry results. J Clin Pathol 2011;64:1019–20.10.1136/jclinpath-2011-200206Search in Google Scholar PubMed

10. Cornes MR, Sulaiman RA, Whitehead SJ, Othonos N, Ford C, Gama R. Incorrect order of draw of blood samples does not cause potassium EDTA sample contamination. Br J Biomed Sci 2012;69:136–8.10.1080/09674845.2012.12069141Search in Google Scholar

11. Cornes MP, Ford C, Gama R. The order of draw, myth or science. Clin Chem Lab Med 2013;51:e285.10.1515/cclm-2013-0650Search in Google Scholar PubMed

12. Lima-Oliveira G, Lippi G, Salvagno GL, Montagnana M, Picheth G, Guidi GC. Incorrect order of draw could be mitigate the patient safety: a phlebotomy management case report. Biochem Med (Zagreb) 2013;23:218–23.10.11613/BM.2013.026Search in Google Scholar PubMed PubMed Central

13. Salvagno G, Lima-Oliveira G, Brocco G, Danese E, Guidi GC, Lippi G. The order of draw: myth or science? Clin Chem Lab Med 2013:1–5.10.1515/cclm-2013-0412Search in Google Scholar PubMed

14. Cadamuro J, Felder TK, Oberkofler H, Mrazek C, Wiedemann H, Haschke-Becher E. Relevance of EDTA carryover during blood collection. Clin Chem Lab Med 2015;53:1271–8.10.1515/cclm-2014-0944Search in Google Scholar PubMed

15. Cornes MP, Ford C, Gama R. Undetected spurious hypernatraemia wastes health-care resources. Ann Clin Biochem 2011;48 (Pt 1):87–8.10.1258/acb.2010.010200Search in Google Scholar PubMed

16. Logie JJ, Chaloner C. A national survey of specimen contamination in the UK. Ann Clin Biochem 2019;56:219–27.10.1177/0004563218812500Search in Google Scholar PubMed

17. Indevuyst C, Schuermans W, Bailleul E, Meeus P. The order of draw: much ado about nothing? Int J Lab Hematol 2015;37:50–5.10.1111/ijlh.12230Search in Google Scholar PubMed

18. Ricos C, Alvarez V, Cava F, Garcia-Lario JV, Hernandez A, Jimenez CV, et al. Current databases on biological variation: pros, cons and progress. Scand J Clin Lab Inv 1999;59:491–500.10.1080/00365519950185229Search in Google Scholar PubMed

19. Fraser CG. Reference change values. Clin Chem Lab Med 2012;50:807–12.10.1515/cclm.2011.733Search in Google Scholar PubMed

20. Berg JE, Ahee P, Berg JD. Variation in phlebotomy techniques in emergency medicine and the incidence of haemolysed samples. Ann Clin Biochem 2011;48(Pt 6):562–5.10.1258/acb.2011.011099Search in Google Scholar PubMed

21. Simundic AM, Church S, Cornes MP, Grankvist K, Lippi G, Nybo M, 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;53:1321–31.10.1515/cclm-2014-1053Search in Google Scholar PubMed

22. Cornes MP, Davidson F, Darwin L, Gay C, Redpath M, Waldron JL, et al. Multi-centre observational study of spurious hyperkalaemia due to EDTA contamination. Clin Lab 2010;56: 597–9.Search in Google Scholar

23. Bouzid K, Bartkiz A, Bouzainne A, Cherif S, Ramdhani S, Zairi A, et al. How to reduce EDTA contamination in laboratory specimens: a Tunisian experience. Clin Chem Lab Med 2015;53:E9–12.10.1515/cclm-2014-0686Search in Google Scholar PubMed

24. Boink AB, Buckley BM, Christiansen TF, Covington AK, Maas AH, Muller-Plathe O, et al. IFCC recommendation on sampling, transport and storage for the determination of the concentration of ionized calcium in whole blood, plasma and serum. J Automat Chem 1991;13:235–9.10.1155/S1463924691000391Search in Google Scholar PubMed PubMed Central

25. Ceron JJ, Martinez-Subiela S, Hennemann C, Tecles F. The effects of different anticoagulants on routine canine plasma biochemistry. Vet J 2004;167:294–301.10.1016/j.tvjl.2003.09.009Search in Google Scholar PubMed

26. Mohri M, Rezapoor H. Effects of heparin, citrate, and EDTA on plasma biochemistry of sheep: comparison with serum. Res Vet Sci 2009;86:111–4.10.1016/j.rvsc.2008.05.010Search in Google Scholar PubMed

27. van den Besselaar AM, van Zanten AP, Brantjes HM, Elisen MG, van der Meer FJ, Poland DC, et al. Comparative study of blood collection tubes and thromboplastin reagents for correction of INR discrepancies: a proposal for maximum allowable magnesium contamination in sodium citrate anticoagulant solutions. Am J Clin Pathol 2012;138:248–54.10.1309/AJCPGSB5YPJRREEVSearch in Google Scholar PubMed

28. White G. Serum ethylenediaminetetraacetic acid concentrations in routine samples submitted for biochemical analysis. Ann Clin Biochem 2010;47(Pt 5):485–6.10.1258/acb.2010.009306Search in Google Scholar PubMed

Received: 2019-04-24
Accepted: 2019-07-11
Published Online: 2019-08-05
Published in Print: 2019-11-26

© 2019 Walter de Gruyter GmbH, Berlin/Boston

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