Monocyte distribution width (MDW): a useful biomarker to improve sepsis management in Emergency Department

Donatella Poz; Danila Crobu; Elena Sukhacheva; Marco Bruno Luigi Rocchi; Maria Chiara Anelli; Francesco Curcio

doi:10.1515/cclm-2021-0875

Article

Monocyte distribution width (MDW): a useful biomarker to improve sepsis management in Emergency Department

Donatella Poz , Danila Crobu , Elena Sukhacheva , Marco Bruno Luigi Rocchi , Maria Chiara Anelli and Francesco Curcio

Published/Copyright: January 11, 2022

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 60 Issue 3

Abstract

Objectives

Sepsis is a time-dependent and life-threating condition. Despite several biomarkers are available, none of them is completely reliable for the diagnosis. This study aimed to evaluate the diagnostic utility of monocyte distribution width (MDW) to early detect sepsis in adult patients admitted in the Emergency Department (ED) with a five part differential analysis as part of the standard clinical practice.

Methods

A prospective cohort study was conducted on 985 patients aged from 18 to 96 and included in the study between November 2019 and December 2019. Enrolled subjects were classified into four groups based on sepsis-2 diagnostic criteria: control, Systemic Inflammatory Response Syndrome (SIRS), infection and sepsis. The hematology analyzer DxH 900 (Beckman Coulter Inc.) provides the new reportable parameter MDW, included in the leukocyte 5 part differential analysis, cleared by Food and Drug administration (FDA) and European Community In-Vitro-Diagnostic Medical Device (CE IVD) marked as early sepsis indicator (ESId).

Results

MDW was able to differentiate the sepsis group from all other groups with Area Under the Curve (AUC) of 0.849, sensitivity of 87.3% and specificity of 71.7% at cut-off of 20.1. MDW in combination with white blood cell (WBC) improves the performance for sepsis detection with a sensitivity increased up to 96.8% when at least one of the two biomarkers are abnormal, and a specificity increased up to 94.6% when both biomarkers are abnormal.

Conclusions

MDW can predict sepsis increasing the clinical value of Leukocyte 5 Part Differential analysis and supporting the clinical decision making in sepsis management at the admission to the ED.

Keywords: biomarker; blood; Emergency Department; infection; monocyte; monocyte distribution width (MDW); sepsis; systemic inflammatory response syndrome (SIRS)

Corresponding author: Francesco Curcio, p.le S. Maria della Misericordia 33100, Udine, Italy; Department of Laboratory Medicine, Institute of Clinical Pathology, University Hospital of Udine, Udine, Italy; and Department of Medicine (DAME), University Hospital of Udine, Udine, Italy, E-mail: francesco.curcio@uniud.it

Funding source: Beckman Coulter Srl

Award Identifier / Grant number: DAME Dept. Council Approval 10/15/2019

Acknowledgments

The authors would like to thank Corin Evans for proofreading the article.

Research funding: Beckman Coulter Srl sponsored the study through a grant to Department of Medicine (DAME), University Hospital of Udine, Udine, Italy.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Author MBLG has consulting agreement with Beckman Coulter Srl. Authors DC and MCA are employees of Beckman Coulter Srl, the sponsor of the project. ES is employee of Beckman Coulter Eurocenter.
Informed consent: Not applicable.
Ethical approval: No further procedures (including blood collection or other diagnostic investigations) were requested in addition to the patient’s standard care pathway and the written informed consent was exempted, in accordance with the guidelines established by the Local Ethics Committee Department of Medicine (DAME); all data were anonymized before analysis.

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;315:801–10. https://doi.org/10.1001/jama.2016.0287.Search in Google Scholar

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. Kaukonen, KM, Bailey, M, Suzuki, S, Pilcher, D, Bellomo, R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012. JAMA 2014;311:1308–16. https://doi.org/10.1001/jama.2014.2637.Search in Google Scholar

4. Esper, AM, Martin, GS. Extending international sepsis epidemiology: the impact of organ dysfunction. Crit Care 2009;13:120–2. https://doi.org/10.1186/cc7704.Search in Google Scholar

5. Blanco, J, Muriel-Bombín, A, Sagredo, V, Taboada, F, Gandía, F, Tamayo, L, et al.. Grupo de Estudios y Análisis en Cuidados Intensivos. Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study. Crit Care 2008;12:R158. https://doi.org/10.1186/cc7157.Search in Google Scholar

6. Harrison, DA, Welch, CA, Eddleston, JM. The epidemiology of severe sepsis in England, Wales and Northern Ireland, 1996 to 2004: secondary analysis of a high quality clinical database, the ICNARC Case Mix Programme Database. Crit Care 2006;10:R42. https://doi.org/10.1186/cc4854.Search in Google Scholar

7. Danai, P, Martin, GS. Epidemiology of sepsis: recent advances. Curr Infect Dis Rep 2005;7:329–34. https://doi.org/10.1007/s11908-005-0005-1.Search in Google Scholar

8. Astiz, M, Saha, D, Lustbader, D, Lin, R, Rackow, E. Monocyte response to bacterial toxins, expression of cell surface receptors, and release of anti-inflammatory cytokines during sepsis. J Lab Clin Med 1996;128:594–600. https://doi.org/10.1016/s0022-2143(96)90132-8.Search in Google Scholar

9. Sfeir, T, Saha, DC, Astiz, M, Rackow, EC. Role of interleukin-10 in monocyte hyporesponsiveness associated with septic shock. Crit Care Med 2001;29:129–33. https://doi.org/10.1097/00003246-200101000-00026.Search in Google Scholar PubMed

10. Saha, DC, Astiz, ME, Eales-Reynolds, LJ, Rackow, EC. Lipopolysaccharide- and superantigen-modulated superoxide production and monocyte hyporesponsiveness to activating stimuli in sepsis. Shock 2012;38:43–8. https://doi.org/10.1097/shk.0b013e318257ed62.Search in Google Scholar

11. Polilli, E, Sozio, F, Frattari, A, Persichitti, L, Sensi, M, Posata, R, et al.. Comparison of monocyte distribution width (MDW) and procalcitonin for early recognition of sepsis. PLoS One 2020;15:e0227300. https://doi.org/10.1371/journal.pone.0227300.Search in Google Scholar PubMed PubMed Central

12. Crouser, ED, Parrillo, JE, Seymour, C, Angus, DC, Bicking, K, Tejidor, L, et al.. Improved early detection of sepsis in the ED with a novel monocyte distribution width biomarker. Chest 2017;152:518–26. https://doi.org/10.1016/j.chest.2017.05.039.Search in Google Scholar PubMed PubMed Central

13. Crouser, ED, Parrillo, JE, Seymour, CW, Angus, DC, Bicking, K, Esguerra, VG, et al.. Monocyte distribution width: a novel indicator of sepsis-2 and sepsis-3 in high-risk emergency department patients. Crit Care Med 2019;47:1018–25. https://doi.org/10.1097/ccm.0000000000003799.Search in Google Scholar PubMed PubMed Central

14. Crouser, ED, Parrillo, JE, Martin, GS, Huang, DT, Hausfater, P, Grigorov, I, et al.. Monocyte distribution width enhances early sepsis detection in the emergency department beyond SIRS and qSOFA. J Intensive Care 2020;33:8–17. https://doi.org/10.1186/s40560-020-00446-3.Search in Google Scholar PubMed PubMed Central

15. Agnello, L, Bivona, G, Vidali, M, Scazzone, C, Giglio, RV, Iacolino, G, et al.. Monocyte distribution width (MDW) as a screening tool for sepsis in the Emergency Department. Clin Chem Lab Med 2020;58:1951–7. https://doi.org/10.1515/cclm-2020-0417.Search in Google Scholar PubMed

16. Levy, MM, Fink, MP, Marshall, JC, Abraham, E, Angus, D, Cook, D, et al.. 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Intensive Care Med 2003;29:530–8. https://doi.org/10.1007/s00134-003-1662-x.Search in Google Scholar PubMed

17. Liu, VX, Fielding-Singh, V, Greene, JD, Baker, JM, Iwashyna, TJ, Bhattacharya, J, et al.. The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med 2017;196:856–63. https://doi.org/10.1164/rccm.201609-1848oc.Search in Google Scholar PubMed PubMed Central

18. Pruinelli, L, Westra, BL, Yadav, P, Hoff, A, Steinbach, M, Kumar, V, et al.. Delay within the 3-hour surviving sepsis campaign guideline on mortality for patients with severe sepsis and septic shock. Crit Care Med 2018;46:500–5. https://doi.org/10.1097/ccm.0000000000002949.Search in Google Scholar

19. Kim, MJ, Cheng, G, Agrawal, DK. Cl-channels are expressed in human normal monocytes: a functional role in migration, adhesion and volume change. Clin Exp Immunol 2004;138:453–9. https://doi.org/10.1111/j.1365-2249.2004.02635.x.Search in Google Scholar PubMed PubMed Central

20. Leckie, MJ, Bryan, SA, Khan, J, Dewar, A, Aikman, SL, McGrath, J, et al.. Automated quantitation of circulating neutrophil and eosinophil activation in asthmatic patients. Thorax 2000;55:471–7. https://doi.org/10.1136/thorax.55.6.471.Search in Google Scholar PubMed PubMed Central

21. Krause, JR. Automated differentials in the hematology laboratory. Am J Clin Pathol 1990;93:S11–6.Search in Google Scholar

22. Richardson-Jones, A. An automated hematology instrument for comprehensive WBC, RBC, and platelet analysis. Am Clin Lab 1990;9:18–22.Search in Google Scholar

23. Lee, AJ, Kim, SG. Mean cell volumes of neutrophils and monocytes are promising markers of sepsis in elderly patients. Blood Res 2013;48:193–7. https://doi.org/10.5045/br.2013.48.3.193.Search in Google Scholar PubMed PubMed Central

24. Park, DH, Park, K, Park, J, Park, HH, Chae, H, Lim, J, et al.. Screening of sepsis using leukocyte cell population data from the Coulter automatic blood cell analyzer DxH800. Int J Lab Hematol 2011;33:391–9. https://doi.org/10.1111/j.1751-553x.2011.01298.x.Search in Google Scholar PubMed

25. Pradier, O, Dimoula, K, Kassengera, Z, Vincent, JL. Diagnosis of sepsis in intensive care; role of the cell population data of the hematology analyzer DxH 800 and expression of CD64 on neutrophils analysed by the platform hematoflow. Int J Lab Hematol 2012;34 S1 PM49:43–173.Search in Google Scholar

26. Dilmoula, K, Kassengera, Z, Turkan, H, Dalcomune, D, Sukhachev, D, Vincent, JL, et al.. Volume, conductivity and scatter properties of leukocytes (VCS Technology) in detecting sepsis in critically ill adult patients. Blood 2011;118:4729. https://doi.org/10.1182/blood.v118.21.4729.4729.Search in Google Scholar

27. Agnello, L, Lo Sasso, B, Bivona, G, Gambino, CM, Giglio, RV, Iacolino, G, et al.. Reference interval of monocyte distribution width (MDW) in healthy blood donors. Clin Chim Acta 2020;510:272–7. https://doi.org/10.1016/j.cca.2020.07.036.Search in Google Scholar PubMed

28. Hausfater, P, Robert Boter, N, 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

29. Wang, HE, Shapiro, NI, Angus, DC, Yealy, DM. National estimates of severe sepsis in United States emergency departments. Crit Care Med 2007;35:1928–36. https://doi.org/10.1097/01.ccm.0000277043.85378.c1.Search in Google Scholar PubMed

30. Agnello, L, Sasso, BL, Giglio, RV, Bivona, G, Gambino, CM, Cortegiani, A, et al.. Monocyte distribution width as a biomarker of sepsis in the intensive care unit: a pilot study. Ann Clin Biochem 2021;58:70–3. https://doi.org/10.1177/0004563220970447.Search in Google Scholar PubMed

31. Piva, E, Zun, J, Pelloso, M, Tosato, F, Fogar, P, Plebani, M. Monocyte distribution width (MDW) parameter as a sepsis indicator in intensive care units. Clin Chem Lab Med 2021;59:1307–14. https://doi.org/10.1515/cclm-2021-0192.Search in Google Scholar PubMed

32. McLymont, N, Glover, GW. Scoring systems for the characterization of sepsis and associated outcomes. Ann Transl Med 2016;4:527. https://doi.org/10.21037/atm.2016.12.53.Search in Google Scholar PubMed PubMed Central

33. Pradhan, S, Ghimire, A, Bhattarai, B, Khanal, B, Pokharel, K, Lamsal, M, et al.. The role of C-reactive protein as a diagnostic predictor of sepsis in a multidisciplinary Intensive Care Unit of a tertiary care center in Nepal. Indian J Crit Care Med 2016;2:417–20. https://doi.org/10.4103/0972-5229.186226.Search in Google Scholar PubMed PubMed Central

34. Mikkelsen, ME, Miltiades, AN, Gaieski, DF, Goyal, M, Fuchs, BD, Shah, CV, et al.. Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock. Crit Care Med 2009;37:1670–7. https://doi.org/10.1097/ccm.0b013e31819fcf68.Search in Google Scholar

35. Bakker, J, Gris, P, Coffernils, M, Kahn, RJ, Vincent, JL. Serial blood lactate levels can predict the development of multiple organ failure following septic shock. Am J Surg 1996;171:221–6. https://doi.org/10.1016/s0002-9610(97)89552-9.Search in Google Scholar

36. Waeschle, RM, Moerer, O, Hilgers, R, Herrmann, P, Neumann, P, Quintel, M. The impact of the severity of sepsis on the risk of hypoglycaemia and glycaemic variability. Crit Care 2008;12:R129. https://doi.org/10.1186/cc7097.Search in Google Scholar PubMed PubMed Central

Received: 2021-12-01

Accepted: 2021-12-29

Published Online: 2022-01-11

Published in Print: 2022-02-23

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Keywords for this article

biomarker; blood; Emergency Department; infection; monocyte; monocyte distribution width (MDW); sepsis; systemic inflammatory response syndrome (SIRS)