Biomarker, Early sepsis, Immature granulocyte, Procalcitonin, Sepsis, Sysmex
Citation Information :
Bhansaly P, Mehta S, Sharma N, Gupta E, Mehta S, Gupta S. Evaluation of Immature Granulocyte Count as the Earliest Biomarker for Sepsis. Indian J Crit Care Med 2022; 26 (2):216-223.
Background: Diagnosing sepsis early is important for its successful management. Various biomarkers are being used currently, but mostly they are either expensive or not readily available. This study aims to evaluate usefulness of automated immature granulocyte count (IG#) and immature granulocyte percentage (IG%) as early diagnostic markers of sepsis and compares it to other established predictive markers.
Patients and methods: In this prospective observational study, 137 eligible, critically ill, nonseptic intensive care unit patients were analyzed for automated IG#, IG%, serum procalcitonin (PCT), and blood lactate (Lac), daily for 7 days after recruitment. Patients were followed for the development of sepsis, defined by the new Sepsis-3 criteria. The study was divided into four time periods of 24 hours each with respect to the day of developing organ dysfunction. Using area under receiver operator characteristic and diagnostic odds ratio (DOR) methods, the best biomarker for the prediction of sepsis in each time period was calculated.
Results: IG# and IG% were the earliest biomarkers to have a significant discriminating value with area under the curve of 0.81 and 0.82, respectively, as early as 24 hours before clinical sepsis is diagnosed by Sepsis-3 criteria. Both IG# and IG% have a high DOR of 34.91 and 18.11, respectively, when compared to others like PCT and Lac having a DOR of 27.06 and 4.78, respectively.
Conclusion: IG# and IG% are easily available, rapid, and inexpensive tools to differentiate between septic and nonseptic patients with high specificity and sensitivity. It is the earliest biomarker to show a significant rise in patients developing sepsis.
Todi S, Chatterjee S, Sahu S, Bhattacharyya M. Epidemiology of severe sepsis in India: an update. Crit Care 2010;14(Suppl. 1):382. DOI: 10.1186/cc8614.
Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, et al. Sepsis in European intensive care units: results of the soap study. Crit Care Med 2006;34(2):344–353. DOI: 10.1097/01.ccm.0000194725.48928.3a.
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013;41(2):580–637. DOI: 10.1097/CCM.0b013e31827e83af.
Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006;34(6):1589–1596. DOI: 10.1097/01.CCM.0000217961.75225.E9.
Van Der Meer W, Van Gelder W, De Keijzer R, Willems H. Does the band cell survive the 21st century? Eur J Haematol 2006;76(3):251–254. DOI: 10.1111/j.1600-0609.2005.00597.x.
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. DOI: 10.1186/1471-2172-14-8.
Divatia JV, Amin PR, Ramakrishnan N, Kapadia FN, Todi S, Sahu S, et al. Intensive care in India: The Indian intensive care case mix and practice patterns study. Indian J Crit Care Med 2016;20(4):216–225. DOI: 10.4103/0972-5229.180042.
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). Journal of the American Medical Association 2016;315(8):801–810. DOI: 10.1001/jama.2016.0287.
Kovach MA, Standiford TJ. The function of neutrophils in sepsis. Curr Opin Infect Dis 2012;25(3):321–327. DOI: 10.1097/QCO.0b013e3283528c9b.
Shen BJ, Ekert H, Tauro GP, Balderas A. Left shift in the peripheral blood count at diagnosis in acute lymphocytic leukemia is significantly correlated with duration of complete remission. Blood 1984;63(1):216–218. DOI: 10.1182/blood.V18.104.22.168.
Bone RC, Balk RA, Cerra FB, Knaus WA, Schein RMH, Sibbald WJ, et al. 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(6):864–874. DOI: 10.1378/chest.101.6.1644.
Buoro S, Mecca T, Vavassori M, Azza G, Espos SA, Dominoni P, et al. Immature granulocyte count on the new Sysmex XN-9000: performance and diagnosis of sepsis in the intensive care unit. Signa Vitae 2015;10(2):54–64. DOI: 10.22514/SV102.122015.4.
Bourne S, Ma N, Gulati G, Gong J. Evaluation of automated versus manual immature granulocyte counts. Lab Med 2013;44(3):282–287. DOI: 10.1309/LMF0OBUBPMWPOKS1.
MacQueen BC, Christensen RD, Yoder BA, Henry E, Baer VL, Bennett ST, et al. Comparing automated vs manual leukocyte differential counts for quantifying the ‘left shift’ in the blood of neonates. J Perinatol 2016;36(10):843–848. DOI:10.1038/jp.2016.92.
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(1):36–43. DOI: 10.3109/00365513.2014.965736.
Senthilnayagam B, Kumar T, Sukumaran J, Jeya M. Automated measurement of immature granulocytes. Performance characteristics and utility in routine clinical practice. Pathol Res Int 2012;2012:483670. DOI: 10.1155/2012/483670.
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(4):523–527. DOI: 10.1016/j.jcrc.2014.03.033.
Ayres LS, Sgnaolin V, Munhoz TP. Immature granulocytes index as early marker of sepsis. Int J Lab Hematol 2019;41(3):392–396. DOI: 10.1111/ijlh.12990.
Buoro S, Mecca T, Azzarà G, Apassiti Esposito S, Seghezzi M, Vavassori M, et al. Extended leukocyte differential count and C-reactive protein in septic patients with liver impairment: diagnostic approach to evaluate sepsis in intensive care unit. Ann Transl Med 2015;3(17):244. DOI: 10.3978/j.issn.2305-5839.2015.09.41.
Roehrl MHA, Lantz D, Sylvester C, Wang JY. Age dependent reference ranges for automated assessment of immature granulocytes and clinical significance in an outpatient setting. Arch Pathol Lab Med 2011;135(4):471–477. DOI: 10.1043/2010-0258-OA.1.
Ansari-Lari MA, Kickler TS, Borowitz MJ. Immature granulocyte measurement using the Sysmex XE-2100 – relationship to infection and sepsis. Am J Clin Pathol 2003;120(5):795–799. DOI: 10.1309/LT30BV9UJJV9CFHQ.