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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 / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

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Volume 58, Issue 2


Serum or plasma? An old question looking for new answers

Mario PlebaniORCID iD: https://orcid.org/0000-0002-0270-1711 / Giuseppe Banfi
  • Direttore Scientifico, IRCCS Istituto Ortopedico Galeazzi, Università Vita e Salute San Raffaele, Milan, Italy
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Sergio Bernardini / Francesco Bondanini
  • Unità Operativa Complessa Patologia Clinica Presidio, Ospedaliero Sant’Eugenio/CTO ASL Roma 2, Rome, Italy
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Laura Conti / Romolo Dorizzi / Fulvio Enrico Ferrara
  • Direttore Servizio Integrato di Medicina di Laboratorio e Anatomia Patologica, Centro Diagnostico Italiano Spa, Milan, Italy
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Rita Mancini / Tommaso Trenti
  • Dipartimento di Medicina di Laboratorio e Anatomia Patologica Azienda Ospedaliera Universitaria e USL di Modena, Modena, Italy
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2019-09-17 | DOI: https://doi.org/10.1515/cclm-2019-0719


Serum or plasma? An old question looking for new answers. There is a continual debate on what type of sample a clinical laboratory should use. While serum is still considered the gold standard and remains the required sample for some assays, laboratories must consider turn-around time, which is an important metric for laboratory performance and, more importantly, plays a critical role in patient care. In addition, a body of evidence emphasise the choice of plasma in order to prevent modifications of some analytes due to the coagulation process and related interferences. Advantages and disadvantages of serum and plasma are discussed on the basis of current literature and evidence. In addition, data are provided on the current utilisation of the samples (serum or plasma) in Italy and in other countries. Finally, a rationale for a possible switch from serum to plasma is provided.

Keywords: anticoagulants; clinical laboratory; plasma; sample of choice; serum; whole blood


  • 1.

    Lum G, Gambino SR. A comparison of serum versus heparinized plasma for routine chemistry tests. Am J Clin Pathol 1974;61:108–13.CrossrefPubMedGoogle Scholar

  • 2.

    Ladenson JH, Tsai LM, Michael JM, Kessler G, Joist JH. Serum versus heparinized plasma for eighteen common chemistry tests. Am J Clin Pathol 1974;62:545–52.PubMedCrossrefGoogle Scholar

  • 3.

    Doumas BT, Hause LL, Simuncak DM, Breitenfeld D. Differences between values for plasma and serum in tests performed in the Ektachem 700 XR Analyzer, and evaluation of “plasma separator tubes (PST)”. Clin Chem 1989;35:151–3.PubMedGoogle Scholar

  • 4.

    Ebert SC, Leroy M, Darcey B. Comparison of aminoglycoside concentrations measured in plasma versus serum. Ther Drug Monit 1989;11:44–6.CrossrefPubMedGoogle Scholar

  • 5.

    Racine JF, Caya S, Delvin EE. Suitability of lithium heparinate plasma for the measurement of selected analytes on Beckman Synchron CX analyzers. Clin Biochem 1996;29:493–5.PubMedCrossrefGoogle Scholar

  • 6.

    Donnelly JG, Soldin SJ, Nealon DA, Hicks JM. Is heparinized plasma suitable for use in routine biochemistry? Pediatr Pathol Lab Med 1995;15:555–9.CrossrefPubMedGoogle Scholar

  • 7.

    Soffiati G, Giavarina D. Stat laboratory testing: integration or autonomy? Clin Chem Lab Med 2010;48:927–30.Web of SciencePubMedGoogle Scholar

  • 8.

    Dolci A, Giavarina D, Pasqualetti S, Panteghini M. Total laboratory automation: do stat tests still matter? Clin Biochem 2017;50:605–11.Web of ScienceCrossrefPubMedGoogle Scholar

  • 9.

    Tate J, Ward G. Interferences in immunoassay. Clin Biochem Rev 2004;25:105–20.PubMedGoogle Scholar

  • 10.

    Kazmierczak SC, Sekhon H, Richards C. False-positive troponin I measured with the Abbott AxSYM attributed to fibrin interference. Int J Cardiol 2005;101:27–31.PubMedCrossrefGoogle Scholar

  • 11.

    Lippi G, Giavarina D, Gelati M, Salvagno GL. 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;429:143–6.Web of ScienceCrossrefGoogle Scholar

  • 12.

    Pasqualetti S, Szőke D, Panteghini M. Heparinate but not serum tubes are susceptible to hemolysis by pneumatic tube transportation. Clin Chem Lab Med 2016;54:785–9.Web of SciencePubMedGoogle Scholar

  • 13.

    Mohamadkhani A, Poustchi H. Repository of human blood derivative biospecimens in biobank: technical implications. Middle East J Dig Dis 2015;7:61–8.PubMedGoogle Scholar

  • 14.

    Ishikawa M, Maekawa K, Saito K, Senoo Y, Urata M, Murayama M, et al. Plasma and serum lipidomics of healthy white adults shows characteristic profiles by subjects’ gender and age. PLoS One 2014;9:e91806.Web of SciencePubMedCrossrefGoogle Scholar

  • 15.

    Lippi G, Salvagno GL, Danese E, Lima-Oliveira G, Brocco G, Guidi GC. Inversion of lithium heparin gel tubes after centrifugation is a significant source of bias in clinical chemistry testing. Clin Chim Acta 2014;436:183–7.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 16.

    Padoan A, Zaninotto M, Piva E, Sciacovelli L, Aita A, TasinatoA, et al. Quality of plasma samples and BD Vacutainer Barricor tubes: effects of centrifugation. Clin Chim Acta 2018;483:271–4.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 17.

    Grzych G, Pekar JD, Maboudou P. Better glucose stability in serum than in plasma samples after 12-h stay at room temperature. Diabetes Technol Ther 2019;21:413–4.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 18.

    Balboni F, Burbui S, Lippi G. Glucose variation in centrifuged serum and lithium-heparin gel tubes stored for up to 96hours at room temperature or 4°C. Scand J Clin Lab Invest 2018;78: 546–50.CrossrefGoogle Scholar

  • 19.

    Grzych G, Pekar JD, Maboudou P, Lippi G. Leucocytosis-induced plasma hyperkalaemia in samples conveyed by a pneumatic transport system: tips and tricks. Br J Haematol 2019;186:e71–3.PubMedWeb of ScienceGoogle Scholar

  • 20.

    Bowen RA, Remaley AT. Interferences from blood collection tube components on clinical chemistry assays. Biochem Med (Zagreb) 2014;24:31–44.PubMedGoogle Scholar

  • 21.

    Demonte D, Pucci M, Salvagno GL, Lippi G. Can citrate plasma be used in exceptional circumstances for some clinical chemistry and immunochemistry tests? Diagnosis (Berl) 2019 May 4. doi: 10.1515/dx-2019-0027 [Epub ahead of print].Google Scholar

  • 22.

    Daves M, Lippi G, Cosio G, Raffagnini A, Peer E, Dangella A, et al. An unusual case of a primary blood collection tube with floating separator gel. J Clin Lab Anal 2012;26:246–7.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 23.

    Cervellin G, Aloe R, Lippi G. A case of factitious hyponatremia and hypokalemia due to the presence of fibrin gel in serum. Diagnosis 2015;2:73–4.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 24.

    Lippi G, Giavarina D, Montagnana M. National survey on the pre-analytical variability in a representative cohort of Italian laboratories. Clin Chem Lab Med. 2006;44:1491–4.Google Scholar

  • 25.

    Lippi G, Giavarina D. Indagine conoscitiva su matrice biologica e gestione della fase preanalitica nei laboratoriclinici. Biochim Clin 2017;41:142–7.Google Scholar

  • 26.

    Woltering EA, Hilton RS, Zolfoghary CM, Thomson J, Zietz S, Go VL, et al. Validation of serum versus plasma measurements of chromogranin A levels in patients with carcinoid tumours: lack of correlation between absolute chromogranin A levels and symptom frequency. Pancreas 2006;33:250–4.CrossrefPubMedGoogle Scholar

  • 27.

    Giavarina D, Fortunato A, Barzon E, Church S, Bérubé J, Green S, et al. Evaluation of BD Vacutainer PST II tubes for a wide range of immunoassays. Clin Chem Lab Med 2009;47:237–41.PubMedWeb of ScienceGoogle Scholar

  • 28.

    Denery JR, Nunes AA, Dickerson TJ. Characterization of differences between blood sample matrices in untargeted metabolomics. Anal Chem 2011;83:1040–7.Web of SciencePubMedCrossrefGoogle Scholar

  • 29.

    Gonzalez-Covarrubias V, Dane A, Hankemeier T, Vreeken RJ. The influence of citrate, EDTA, and heparin anticoagulants to human plasma LC–MS lipidomic profiling. Metabolomics 2013;9:337–48.CrossrefWeb of ScienceGoogle Scholar

  • 30.

    Khadka M, Todor A, Maner-Smith KM, Colucci JK, Tran V, Gaul DA, et al. The effect of anticoagulants, temperature, and time on the human plasma metabolome and lipidome from healthy donors as determined by liquid chromatography-mass spectrometry. Biomolecules 2019;9. pii: E200.Web of SciencePubMedGoogle Scholar

  • 31.

    Lee J-E, Kim SY, Shin S-Y. Effect of repeated freezing and thawing on biomarker stability in plasma and serum samples. Osong Public Health Res Perspect 2015;6:357–62.CrossrefPubMedGoogle Scholar

  • 32.

    Zhou Z, Chen Y, He J, Xu J, Zhang R, Mao Y, et al. Systematic evaluation of serum and plasma collection on the endogenous metabolome. Bioanalysis 2017;9:239–50.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 33.

    ISO 15189:2012 Medical laboratories: particular requirements for quality and competence. Geneva: International Organisation for Standardisation, 2012.Google Scholar

  • 34.

    Da Rin G. Technological solutions in favour or using plasma in routines. 47th National Congress SIBioC, Firenze, 2015.Google Scholar

  • 35.

    Clinical Laboratory Standards Institute (CLSI). Measurement procedure comparison and bias estimates using patient samples, approved guideline, 3rd ed. CLSI guideline EP09c. Wayne, PA: CLSI, 2018.Google Scholar

  • 36.

    Plebani M. Harmonization in laboratory medicine: more than clinical chemistry? Clin Chem Lab Med 2018;56:1579–86.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 37.

    Plebani M, Sciacovelli L, Aita A. Quality indicators for the total testing process. Clin Lab Med 2017;37:187–205.CrossrefWeb of SciencePubMedGoogle Scholar

About the article

Corresponding author: Prof. Mario Plebani, Dipartimento Strutturale Medicina di Laboratorio, Azienda Ospedale Università di Padova, Via Giustiniani, 2, 35128 Padova, Italy, Phone: 0498212792

Received: 2019-07-15

Accepted: 2019-08-22

Published Online: 2019-09-17

Published in Print: 2020-01-28

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.

Potential conflicts of interest: This document was produced with the non-conditional contribution of Becton Dickinson Italia SpA.

Competing interests: The funding organisation(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 58, Issue 2, Pages 178–187, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2019-0719.

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