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Cell population data for early detection of sepsis in patients with suspected infection in the emergency department

  • Marta Cancella De Abreu ORCID logo EMAIL logo , Caren Brumpt , Timothé Sala , Nathalie Oueidat , Martin Larsen and Pierre Hausfater
Published/Copyright: April 11, 2025

Abstract

Objectives

Traditional biomarkers used for sepsis diagnosis have limited sensitivity and specificity and, so far, are not recommended for sepsis diagnosis. We aimed to evaluate diagnostic accuracy of XN-9000® hematology analyzer derived cell population data (CPD) for sepsis.

Methods

We conducted a cross-sectional cohort study on patients admitted to an emergency department (ED) with a suspicion of infection, having a complete blood count with differential (CBC-Diff). CBC-Diff were performed on XN-9000® analyzer (Sysmex, Kobe, Japan). CPD were measured routinely for each CBC-Diff ordered by ED physician. They include: neutrophils-related - Neut-GI and Neut-RI; monocytes-related - Mono-X, Mono-Z, Re-Mono and Mono-Y; IG referring to immature granulocytes; and lymphocytes-related - As-lymp and Re-lymp. Intensive care infection (ICIS) and neutrophile and monocyte (NEMO) scores were calculated using several CPD parameters. Diagnostic performance of each biomarker was computed together with receiver operating characteristic curves for sepsis diagnosis (according to Sepsis-3 definition).

Results

A total of 1,155 patients with a suspicion of infection were included and 230 had sepsis. Median age was 64 years and 49 % were female. Except for lymphocyte count with an area under the receiver operating characteristic (AUROC) of 0.67 (95 % confidential interval 0.63–0.70), the other CPD exhibited modest performances with AUROC under 0.65. The ICIS and NEMO scores had a modest performance with AUROC of 0.56 (0.52–0.61) and 0.55 (0.51–0.59) respectively.

Conclusions

None of the biomarkers and scores tested demonstrated sufficient diagnostic accuracy to be recommended for routine sepsis screening in the ED.


Corresponding author: Marta Cancella De Abreu, Emergency Department, APHP-Sorbonne Université, Hôpital Pitié-Salpêtrière, Paris, France; and GRC-14 BIOSFAST, CIMI, UMR 1135, Sorbonne Université, Paris, France, E-mail:

Funding source: Sysmex Corporation

Acknowledgments

Enfel HOUAS and Ilaria CHERUBINI (our CRA) for their enormous help on data collection and quality control performance daily; Laura WAKSELMAN, Naima ZEMIRLI and Juliette BLONDY (Unité de Recherche Clinique (URC), Hôpitaux Universitaires Pitié Salpêtrière – Charles Foix), for helping with ethical approval; Jeremy CORRIGER, Sorbonne University, for helping in discussion of statistical analysis.

  1. Research ethics: Infectious Ethic Committee (CER-MIT) (in Paris, France) approved the study.

  2. Informed consent: According to the French law, as there were no modifications in standard of care, it was exempted from informed consent. At ED arrival, patients were informed on possible inclusion to this study, in case of sepsis.

  3. Author contributions: MCA – Conceptualization, Methodology, Data review and Management, Formal Analysis, Investigation, Writing TS – Patient’s screening CB – Methodology, Formal Analysis. NO – Methodology, Formal Analysis. ML – Methodology, Statistical Analysis supervision. PH – Conceptualization, Methodology, Funding Acquisition, Supervision, patient’s screening, writing review and editing. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: Sysmex participated in funding the ED clinical research assistants for data collection. Sysmex provided the reagents for measuring CPD free of charge. Sysmex did not had a role in the conceptualization, design, data collection and analysis neither on decision to publish nor on preparation of the manuscript.

  7. Data availability: Not applicable.

References

1. Singer, M, Deutschman, CS, Seymour, CW, Shankar-Hari, M, Annane, D, Bauer, M, et al.. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315:801. https://doi.org/10.1001/jama.2016.0287.Search in Google Scholar PubMed PubMed Central

2. Rudd, KE, Johnson, SC, Agesa, KM, Shackelford, KA, Tsoi, D, Kievlan, DR, et al.. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. Lancet 2020;395:200–11. https://doi.org/10.1016/s0140-6736(19)32989-7.Search in Google Scholar

3. Le Conte, P, Thibergien, S, Obellianne, JB, Montassier, E, Potel, G, Roy, PM, et al.. Recognition and treatment of severe sepsis in the emergency department: retrospective study in two French teaching hospitals. BMC Emerg Med 2017;17:27. https://doi.org/10.1186/s12873-017-0133-6.Search in Google Scholar PubMed PubMed Central

4. Morr, M, Lukasz, A, Rübig, E, Pavenstädt, H, Kümpers, P. Sepsis recognition in the emergency department – impact on quality of care and outcome? BMC Emerg Med 2016;17:11. https://doi.org/10.1186/s12873-017-0122-9.Search in Google Scholar PubMed PubMed Central

5. Levy, MM, Evans, LE, Rhodes, A. The surviving sepsis campaign bundle: 2018 update. Crit Care Med 2018;46. https://doi.org/10.1097/ccm.0000000000003119.Search in Google Scholar

6. Husabø, G, Nilsen, RM, Flaatten, H, Solligård, E, Frich, JC, Bondevik, GT, et al.. Early diagnosis of sepsis in emergency departments, time to treatment, and association with mortality: an observational study. PLoS One 2020;15:e0227652. https://doi.org/10.1371/journal.pone.0227652.Search in Google Scholar PubMed PubMed Central

7. Pierrakos, C, Velissaris, D, Bisdorff, M, Marshall, JC, Vincent, JL. Biomarkers of sepsis: time for a reappraisal. Crit Care 2020;24:287. https://doi.org/10.1186/s13054-020-02993-5.Search in Google Scholar PubMed PubMed Central

8. Faix, JD. Biomarkers of sepsis. Crit Rev Clin Lab Sci 2013;50:23–36. https://doi.org/10.3109/10408363.2013.764490.Search in Google Scholar PubMed PubMed Central

9. Evans, L, Rhodes, A, Alhazzani, W, Antonelli, M, Coopersmith, CM, French, C, et al.. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med 2021;47:1181–247. https://doi.org/10.1007/s00134-021-06506-y.Search in Google Scholar PubMed PubMed Central

10. Somogyi, RD, Sheridan, C, Recent, D. Advances in bedside device-based early detection of sepsis. J Intensive Care Med 2022;37:849–56. https://doi.org/10.1177/08850666211044124.Search in Google Scholar PubMed

11. Urrechaga, E, Bóveda, O, Aguirre, U. Role of leucocytes cell population data in the early detection of sepsis. J Clin Pathol 2018;71:259–66. https://doi.org/10.1136/jclinpath-2017-204524.Search in Google Scholar PubMed

12. Buoro, S, Seghezzi, M, Vavassori, M, Dominoni, P, Esposito, SA, Manenti, B, et al.. Clinical significance of cell population data (CPD) on Sysmex XN- 9000 in septic patients with our without liver impairment. Ann Transl Med 2016;4. https://doi.org/10.21037/atm.2016.10.73.Search in Google Scholar PubMed PubMed Central

13. Park, SH, Park, CJ, Lee, BR, Nam, KS, Kim, MJ, Han, MY, et al.. Sepsis affects most routine and cell population data (CPD) obtained using the S ysmex XN ‐2000 blood cell analyzer: neutrophil‐related CPD NE ‐ SFL and NE ‐ WY provide useful information for detecting sepsis. Int J Lab Hematol 2015;37:190–8. https://doi.org/10.1111/ijlh.12261.Search in Google Scholar PubMed

14. Luo, Y, Lin, J, Chen, H, Zhang, J, Peng, S, Kuang, M. Utility of neut-X, neut-Y and neut-Z parameters for rapidly assessing sepsis in tumor patients. Clin Chim Acta 2013;422:5–9. https://doi.org/10.1016/j.cca.2013.03.026.Search in Google Scholar PubMed

15. Ha, SO, Park, SH, Park, SH, Park, JS, Huh, JW, Lim, CM, et al.. Fraction of immature granulocytes reflects severity but not mortality in sepsis. Scand J Clin Lab Invest 2015;75:36–43. https://doi.org/10.3109/00365513.2014.965736.Search in Google Scholar PubMed

16. Litell, JM, Guirgis, F, Driver, B, Jones, AE, Puskarich, MA. Most emergency department patients meeting sepsis criteria are not diagnosed with sepsis at discharge. Acad Emerg Med 2021;28:745–52. https://doi.org/10.1111/acem.14265.Search in Google Scholar PubMed PubMed Central

17. Cornet, E, Boubaya, M, Troussard, X. Contribution of the new XN‐1000 parameters NEUT‐RI and NEUT‐WY for managing patients with immature granulocytes. Int J Lab Hematol [Internet] 2015;37. https://doi.org/10.1111/ijlh.12372.Search in Google Scholar PubMed

18. Van Der Geest, PJ, Mohseni, M, Linssen, J, Duran, S, de Jonge, R, Groeneveld, ABJ. The intensive care infection score – a novel marker for the prediction of infection and its severity. Crit Care 2016;20. https://doi.org/10.1186/s13054-016-1366-6.Search in Google Scholar PubMed PubMed Central

19. Hausfater, P, Robert, BN, Morales Indiano, C, Cancella De Abreu, M, Marin, AM, Pernet, J, et al.. Monocyte distribution width (MDW) performance as an early sepsis indicator in the emergency department: comparison with CRP and procalcitonin in a multicenter international European prospective study. Crit Care 2021;25:227. https://doi.org/10.1186/s13054-021-03622-5.Search in Google Scholar PubMed PubMed Central

20. Nierhaus, A, Klatte, S, Linssen, J, Eismann, NM, Wichmann, D, Hedke, J, et al.. Revisiting the white blood cell count: immature granulocytes count as a diagnostic marker to discriminate between SIRS and sepsis - a prospective, observational study. BMC Immunol 2013;14:8. https://doi.org/10.1186/1471-2172-14-8.Search in Google Scholar PubMed PubMed Central

21. Buoro1, S, Seghezzi, M, Vavassori, M, Dominoni, P, Apassiti Esposito, S, Manenti, B, et al.. Clinical significance of cell population data (CPD) on Sysmex XN-9000 in septic patients with our without liver impairment. Ann Transl Med 2016;4:418. https://doi.org/10.21037/atm.2016.10.73.Search in Google Scholar PubMed PubMed Central

22. Jha, B, Goel, S, Singh, MK, Sethi, M, Deswal, V, Kataria, S, et al.. Value of new advanced hematological parameters in early prediction of severity of COVID ‐19. Int J Lab Hematol 2023;45:282–8. https://doi.org/10.1111/ijlh.14035.Search in Google Scholar PubMed

23. Cancella De Abreu, M, Sala, T, Houas, E, Cherubini, I, Larsen, M, Hausfater, P. Clinical impact of the implementation of monocyte distribution width (MDW) measurement on time to anti-infective administration in sepsis patients in the emergency department: a before/after cohort study. Crit Care 2024;28:346. https://doi.org/10.1186/s13054-024-05141-5.Search in Google Scholar PubMed PubMed Central

24. Velissaris, D, Zareifopoulos, N, Lagadinou, M, Platanaki, C, Tsiotsios, K, Stavridis, EL, et al.. Procalcitonin and sepsis in the emergency department: an update. Eur Rev Med Pharmacol Sci 2021;25:466–79. https://doi.org/10.26355/eurrev_202101_24416.Search in Google Scholar PubMed

25. Hotchkiss, RS, Monneret, G, Payen, D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol 2013;13:862–74. https://doi.org/10.1038/nri3552.Search in Google Scholar PubMed PubMed Central

26. Borregaard, N. Neutrophils, from marrow to microbes. Immunity 2010;33:657–70. https://doi.org/10.1016/j.immuni.2010.11.011.Search in Google Scholar PubMed

27. Murao, A, Aziz, M, Wang, P. Neutrophil heterogeneity in sepsis: the role of DAMPs. Shock 2022;59:239–46. https://doi.org/10.1097/shk.0000000000002019.Search in Google Scholar PubMed PubMed Central

28. Zhang, X, Zhang, Y, Yuan, S, Zhang, J. The potential immunological mechanisms of sepsis. Front Immunol 2024;15:1434688. https://doi.org/10.3389/fimmu.2024.1434688.Search in Google Scholar PubMed PubMed Central

29. Yao, RQ, Zhao, PY, Li, ZX, Liu, YY, Zheng, LY, Duan, Y, et al.. Single-cell transcriptome profiling of sepsis identifies HLA-DRlowS100Ahigh monocytes with immunosuppressive function. Mil Med Res 2023;10:27. https://doi.org/10.1186/s40779-023-00462-y.Search in Google Scholar PubMed PubMed Central

30. Seghezzi, M, Buoro, S, Previtali, G, Moioli, V, Manenti, B, Simon-Lopez, R, et al.. A preliminary proposal for quality control assessment and harmonization of leukocytes morphology-structural parameters (cell population data parameters). J Med Biochem 2018;37:486–98. https://doi.org/10.2478/jomb-2018-0005.Search in Google Scholar PubMed PubMed Central

31. Hoffmann, JJML. Cell population data: much more to explore. Clin Chem Lab Med 2023;61:377–9. https://doi.org/10.1515/cclm-2022-1173.Search in Google Scholar PubMed


Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2025-0180).


Received: 2025-02-14
Accepted: 2025-03-24
Published Online: 2025-04-11
Published in Print: 2025-07-28

© 2025 Walter de Gruyter GmbH, Berlin/Boston

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