Skip to main content
Top
Published in: Critical Care 1/2015

Open Access 01-12-2015 | Research

The diagnostic and prognostic significance of monitoring blood levels of immature neutrophils in patients with systemic inflammation

Authors: Tracey Anne Mare, David Floyd Treacher, Manu Shankar-Hari, Richard Beale, Sion Marc Lewis, David John Chambers, Kenneth Alun Brown

Published in: Critical Care | Issue 1/2015

Login to get access

Abstract

Introduction

In this cohort study, we investigated whether monitoring blood levels of immature neutrophils (myelocytes, metamyelocytes and band cells) differentiated patients with sepsis from those with the non-infectious (N-I) systemic inflammatory response syndrome (SIRS). We also ascertained if the appearance of circulating immature neutrophils was related to adverse outcome.

Methods

Blood samples were routinely taken from 136 critically ill patients within 48 hours of ICU entry and from 20 healthy control subjects. Clinical and laboratory staff were blinded to each other’s results, and patients were retrospectively characterised into those with SIRS (n = 122) and those without SIRS (n = 14). The patients with SIRS were further subdivided into categories of definite sepsis (n = 51), possible sepsis (n = 32) and N-I SIRS (n = 39). Two established criteria were used for monitoring immature white blood cells (WBCs): one where band cells >10% WBCs and the other where >10% of all forms of immature neutrophils were included but with a normal WBC count. Immature neutrophils in blood smears were identified according to nuclear morphology and cytoplasmic staining.

Results

With the first criterion, band cells were present in most patients with SIRS (mean = 66%) when compared with no SIRS (mean = 29%; P <0.01) and with healthy subjects (0%). The prevalence of band cells was higher in definite sepsis (mean = 82%) than in patients with possible sepsis (mean = 63%; P <0.05) or with N-I SIRS (mean = 39%; P <0.001), and they had a sensitivity of 84% and a specificity of 71% for the detection of definite sepsis. With the second criterion (that is, patients with normal WBC counts), we noted that immature neutrophils did not differentiate any of the patient groups from one another. Patients who died within 1 week of blood sample provision had higher levels of myelocytes and metamyelocytes (median = 9%; P <0.05) than patients who died at 2 to 4 weeks (median =0.5%).

Conclusions

Raised blood levels of band cells have diagnostic significance for sepsis, provided that measurements are not confined to patients with normal WBC counts, whereas an increased prevalence of myelocytes and metamyelocytes may have prognostic application.
Literature
1.
go back to reference Vincent JL, Opal SO, Marshall JC, Tracey KJ. Sepsis definitions, time for a change. Lancet. 2013;381:774–5.CrossRef Vincent JL, Opal SO, Marshall JC, Tracey KJ. Sepsis definitions, time for a change. Lancet. 2013;381:774–5.CrossRef
2.
go back to reference American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992;20:864–74.CrossRef American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992;20:864–74.CrossRef
3.
go back to reference Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31:1250–6.CrossRef Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31:1250–6.CrossRef
4.
go back to reference Benez EI. Hematologic response to acute inflammation: the band neutrophil revisited. Tex Med. 1990;86:26–8. Benez EI. Hematologic response to acute inflammation: the band neutrophil revisited. Tex Med. 1990;86:26–8.
5.
go back to reference Summers C, Rankin SM, Condliffe AM, Singh N, Peters AM, Chilvers ER. Neutrophil kinetics in health and disease. Trends Immunol. 2010;31:318–24.CrossRef Summers C, Rankin SM, Condliffe AM, Singh N, Peters AM, Chilvers ER. Neutrophil kinetics in health and disease. Trends Immunol. 2010;31:318–24.CrossRef
6.
go back to reference Sadik CD, Kim ND, Luster AD. Neutrophils cascading their way to inflammation. Trends Immunol. 2011;32:452–60.CrossRef Sadik CD, Kim ND, Luster AD. Neutrophils cascading their way to inflammation. Trends Immunol. 2011;32:452–60.CrossRef
7.
go back to reference Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013;13:159–75.CrossRef Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013;13:159–75.CrossRef
8.
go back to reference Cornbleet P. Clinical utility of the band count. Clin Lab Med. 2002;22:101–36.CrossRef Cornbleet P. Clinical utility of the band count. Clin Lab Med. 2002;22:101–36.CrossRef
9.
go back to reference Al-Gwaiz LA, Babay HH. The diagnostic value of absolute neutrophil count, band count and morphologic changes of neutrophils in predicting bacterial infections. Med Princ Pract. 2007;16:344–7.CrossRef Al-Gwaiz LA, Babay HH. The diagnostic value of absolute neutrophil count, band count and morphologic changes of neutrophils in predicting bacterial infections. Med Princ Pract. 2007;16:344–7.CrossRef
10.
go back to reference Abraham E, Mathay M, Dinarello C, Vincent J, Cohen J, Opal S, et al. Consensus conference definitions for sepsis, septic shock, acute lung injury, and acute respiratory distress syndrome: time for a reevaluation. Crit Care Med. 2000;28:232–5.CrossRef Abraham E, Mathay M, Dinarello C, Vincent J, Cohen J, Opal S, et al. Consensus conference definitions for sepsis, septic shock, acute lung injury, and acute respiratory distress syndrome: time for a reevaluation. Crit Care Med. 2000;28:232–5.CrossRef
11.
go back to reference Vincent J. Dear SIRS, I’m sorry to say that I don't like you…. Crit Care Med. 1997;25:372–4.CrossRef Vincent J. Dear SIRS, I’m sorry to say that I don't like you…. Crit Care Med. 1997;25:372–4.CrossRef
12.
go back to reference Cavallazzi R, Bennin CL, Hirani A, Gilbert C, Marik PE. Is the band count useful in the diagnosis of infection? An accuracy study in critically ill patients. J Intensive Care Med. 2010;25:353–7.CrossRef Cavallazzi R, Bennin CL, Hirani A, Gilbert C, Marik PE. Is the band count useful in the diagnosis of infection? An accuracy study in critically ill patients. J Intensive Care Med. 2010;25:353–7.CrossRef
13.
go back to reference 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.CrossRef 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.CrossRef
14.
go back to reference Guérin E, Orabona M, Raquil MA, Giraudeau B, Bellier R, Gibot S, et al. Circulating immature granulocytes with T-cell killing functions predict sepsis deterioration. Crit Care Med. 2014;42:2007–18.CrossRef Guérin E, Orabona M, Raquil MA, Giraudeau B, Bellier R, Gibot S, et al. Circulating immature granulocytes with T-cell killing functions predict sepsis deterioration. Crit Care Med. 2014;42:2007–18.CrossRef
15.
go back to reference 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.CrossRef 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.CrossRef
16.
go back to reference Van der Geest PJ, Mohseni M, Brouwer R, van der Hoven B, Steyerberg EW, Groeneveld AB. Immature granulocytes predict microbial infection and its adverse sequelae in the intensive care unit. J Crit Care. 2014;29:523–7.CrossRef Van der Geest PJ, Mohseni M, Brouwer R, van der Hoven B, Steyerberg EW, Groeneveld AB. Immature granulocytes predict microbial infection and its adverse sequelae in the intensive care unit. J Crit Care. 2014;29:523–7.CrossRef
17.
go back to reference Segal AW. How neutrophils kill microbes. Annu Rev Immunol. 2005;23:197–223.CrossRef Segal AW. How neutrophils kill microbes. Annu Rev Immunol. 2005;23:197–223.CrossRef
18.
go back to reference Brown KA, Brain SD, Pearson JD, Edgeworth JD, Lewis SM, Treacher DF. Neutrophils in development of multiple organ failure in sepsis. Lancet. 2006;368:157–69.CrossRef Brown KA, Brain SD, Pearson JD, Edgeworth JD, Lewis SM, Treacher DF. Neutrophils in development of multiple organ failure in sepsis. Lancet. 2006;368:157–69.CrossRef
19.
go back to reference Vincent JL, Abraham E. The last 100 years of sepsis. Am J Respir Crit Care Med. 2006;173:256–63.CrossRef Vincent JL, Abraham E. The last 100 years of sepsis. Am J Respir Crit Care Med. 2006;173:256–63.CrossRef
20.
go back to reference Bermejo-Martín JF, Tamayo E, Ruiz G, Andaluz-Ojeda D, Herrán-Monge R, Muriel-Bombín A, et al. Circulating neutrophil counts and mortality in septic shock. Crit Care. 2014;18:407.CrossRef Bermejo-Martín JF, Tamayo E, Ruiz G, Andaluz-Ojeda D, Herrán-Monge R, Muriel-Bombín A, et al. Circulating neutrophil counts and mortality in septic shock. Crit Care. 2014;18:407.CrossRef
21.
go back to reference European Society of Intensive Care Medicine. The problem of sepsis. Intensive Care Med. 1994;20:300–4.CrossRef European Society of Intensive Care Medicine. The problem of sepsis. Intensive Care Med. 1994;20:300–4.CrossRef
22.
go back to reference Kuppermann N, Walton EA. Immature neutrophils in the blood smears of young febrile children. Arch Pediatr Adolesc Med. 1999;153:261–6.CrossRef Kuppermann N, Walton EA. Immature neutrophils in the blood smears of young febrile children. Arch Pediatr Adolesc Med. 1999;153:261–6.CrossRef
23.
go back to reference Baron RM, Baron M, Perrella M. Pathobiology of sepsis: are we still asking the same questions? Am J Respir Cell Mol Biol. 2006;34:129–34.CrossRef Baron RM, Baron M, Perrella M. Pathobiology of sepsis: are we still asking the same questions? Am J Respir Cell Mol Biol. 2006;34:129–34.CrossRef
24.
go back to reference Chang P, Harris J, Bhumbra N, Puczynski M, Kherallah N, Lewis T, et al. Index of suspicion. Pediatr Rev. 2006;27:73–8.CrossRef Chang P, Harris J, Bhumbra N, Puczynski M, Kherallah N, Lewis T, et al. Index of suspicion. Pediatr Rev. 2006;27:73–8.CrossRef
25.
go back to reference Glasser L, Fiederlein RL. Functional differentiation of normal human neutrophils. Blood. 1987;69:937–44.CrossRef Glasser L, Fiederlein RL. Functional differentiation of normal human neutrophils. Blood. 1987;69:937–44.CrossRef
26.
go back to reference Drifte G, Dunn-Siegrist I, Tissières P, Pugin J. Innate immune functions of immature neutrophils in patients with sepsis and severe systemic inflammatory response syndrome. Crit Care Med. 2013;41:820–32.CrossRef Drifte G, Dunn-Siegrist I, Tissières P, Pugin J. Innate immune functions of immature neutrophils in patients with sepsis and severe systemic inflammatory response syndrome. Crit Care Med. 2013;41:820–32.CrossRef
27.
go back to reference Ward MJ, Fertel BS, Bonomo JB, Smith CL, Hart KW, Lindsell CJ, et al. The degree of bandemia in septic ED patients does not predict inpatient mortality. Am J Emerg Med. 2012;30:181–3.CrossRef Ward MJ, Fertel BS, Bonomo JB, Smith CL, Hart KW, Lindsell CJ, et al. The degree of bandemia in septic ED patients does not predict inpatient mortality. Am J Emerg Med. 2012;30:181–3.CrossRef
28.
go back to reference Cimenti C, Ewra E, Herkner K, Kasper D, Müller W, Resch B. The predictive value of immature granulocyte count and immature myeloid information in the diagnosis of neonatal sepsis. Clin Chem Lab Med. 2012;50:1429–42.CrossRef Cimenti C, Ewra E, Herkner K, Kasper D, Müller W, Resch B. The predictive value of immature granulocyte count and immature myeloid information in the diagnosis of neonatal sepsis. Clin Chem Lab Med. 2012;50:1429–42.CrossRef
29.
go back to reference Chiesa C, Panero A, Osborne J, Simonetti A, Pacifico L. Opinion diagnosis of neonatal sepsis: a clinical and laboratory challenge. Clin Chem. 2004;50:279–87.CrossRef Chiesa C, Panero A, Osborne J, Simonetti A, Pacifico L. Opinion diagnosis of neonatal sepsis: a clinical and laboratory challenge. Clin Chem. 2004;50:279–87.CrossRef
30.
go back to reference Lichtman M, Weed R. Alteration in the cell periphery during granulocyte maturation. Blood. 1972;39:301–16.CrossRef Lichtman M, Weed R. Alteration in the cell periphery during granulocyte maturation. Blood. 1972;39:301–16.CrossRef
31.
go back to reference Linderkamp O, Reuf R, Brenner B, Gulbins E, Lang F. Passive deformability of mature, immature, and active neutrophils in healthy and septicemic neonates. Pediatr Res. 1998;44:946–50.CrossRef Linderkamp O, Reuf R, Brenner B, Gulbins E, Lang F. Passive deformability of mature, immature, and active neutrophils in healthy and septicemic neonates. Pediatr Res. 1998;44:946–50.CrossRef
32.
go back to reference Doerschuk C, Beyers N, Coxon H, Wiggs B, Hogg J. The importance of the neutrophil and capillary diameter in margination of PMN in the lung. J Appl Physiol. 1993;74:3040–5.CrossRef Doerschuk C, Beyers N, Coxon H, Wiggs B, Hogg J. The importance of the neutrophil and capillary diameter in margination of PMN in the lung. J Appl Physiol. 1993;74:3040–5.CrossRef
33.
go back to reference Van Eeden SF, Lawrence E, Sato Y, Kitagawa Y, Hogg JC. Neutrophils released from the bone marrow by granulocyte colony-stimulating factor sequester in lung microvessels but are slow to migrate. Eur Respir J. 2000;15:1079–86.CrossRef Van Eeden SF, Lawrence E, Sato Y, Kitagawa Y, Hogg JC. Neutrophils released from the bone marrow by granulocyte colony-stimulating factor sequester in lung microvessels but are slow to migrate. Eur Respir J. 2000;15:1079–86.CrossRef
34.
go back to reference Downey G, Doherty D, Schwab B, Elson E, Henson P, Scott G. Retention of leukocytes in capillaries: role of cell size and deformability. J Appl Physiol. 1990;69:1767–78.CrossRef Downey G, Doherty D, Schwab B, Elson E, Henson P, Scott G. Retention of leukocytes in capillaries: role of cell size and deformability. J Appl Physiol. 1990;69:1767–78.CrossRef
35.
go back to reference Pöschl JMB, Ruef P, Linderkamp O. Deformability of passive and activated neutrophils in children with Gram-negative septicemia. Scand J Clin Lab Invest. 2005;65:333–9.CrossRef Pöschl JMB, Ruef P, Linderkamp O. Deformability of passive and activated neutrophils in children with Gram-negative septicemia. Scand J Clin Lab Invest. 2005;65:333–9.CrossRef
36.
go back to reference 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.CrossRef 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.CrossRef
37.
go back to reference Park BH, Kang YA, Park MS, Jung WJ, Lee SH, Lee SK, et al. Delta neutrophil index as an early marker of disease severity in critically ill patients with sepsis. BMC Infect Dis. 2011;11:299.CrossRef Park BH, Kang YA, Park MS, Jung WJ, Lee SH, Lee SK, et al. Delta neutrophil index as an early marker of disease severity in critically ill patients with sepsis. BMC Infect Dis. 2011;11:299.CrossRef
38.
go back to reference Bernstein L, Rucinski J. Measurement of granulocyte maturation may improve the early diagnosis of the septic state. Clin Chem Lab Med. 2011;49:2089–95.CrossRef Bernstein L, Rucinski J. Measurement of granulocyte maturation may improve the early diagnosis of the septic state. Clin Chem Lab Med. 2011;49:2089–95.CrossRef
39.
go back to reference Mora-Jenson H, Jendholm J, Fossum A, Porse B, Borregaard N, Theilgaard-Monch K. Immunophenotypical characterization of human neutrophil differentiation. J Leukoc Biol. 2011;90:629–34.CrossRef Mora-Jenson H, Jendholm J, Fossum A, Porse B, Borregaard N, Theilgaard-Monch K. Immunophenotypical characterization of human neutrophil differentiation. J Leukoc Biol. 2011;90:629–34.CrossRef
Metadata
Title
The diagnostic and prognostic significance of monitoring blood levels of immature neutrophils in patients with systemic inflammation
Authors
Tracey Anne Mare
David Floyd Treacher
Manu Shankar-Hari
Richard Beale
Sion Marc Lewis
David John Chambers
Kenneth Alun Brown
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2015
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-015-0778-z

Other articles of this Issue 1/2015

Critical Care 1/2015 Go to the issue