Diagnostic Performance of Immature Granulocytes in the Early Diagnosis of Acute and Perforated Appendicitis in Children: A Retrospective Study

Year 2025, Volume: 7 Issue: 3, 784 - 91, 09.09.2025

Nurcan Çoşkun , İlknur Kaba

Abstract

Aim: Timely identification and intervention in acute appendicitis (AA) are essential to avoid complications. Despite technological advances in diagnostics, challenges persist, particularly in pediatric populations. As a result, the search continues for reliable, rapid, low-cost, and accessible biomarkers. Immature granulocytes (IGs) have recently been proposed as promising indicators of inflammation severity. This study aims to evaluate the diagnostic function of IG and its percentage in distinguishing AA from perforated appendicitis (PA) in pediatric population.
Material and Method: A retrospective study was performed, comprising 201 pediatric cases who had surgery due to appendicitis and 42 healthy controls. Participants were categorized based on histopathological findings into AA, PA, and control groups. Laboratory variables including white blood cell (WBC) count, hemoglobin (Hb), neutrophil-to-lymphocyte ratio (NLR), mean platelet volume (MPV), platelet count (PLT), IG, %IG, and C-reactive protein (CRP) were compared across groups. Diagnostic performance was assessed through Receiver Operating Characteristic (ROC) curve analysis.
Results: No significant variations were observed in PLT and MPV values. However, significant differenc were detected in WBC, CRP, Hb, lymphocyte, monocyte, neutrophil, IG, and %IG levels across the study cohorts (p<0.001 for most; Hb: p=0.001). In PA, IG and %IG showed area under the curve (AUC) values of 0.956 and 0.930. In AA, AUC values were 0.929 for IG and 0.924 for %IG. Cutoff points of 25 (IG) and 0.25 (%IG) yielded good sensitivity and specificity for both conditions.
Conclusion: IG and %IG may provide valuable support in diagnosing AA and PA in pediatric patients. However, their use should complement clinical and laboratory assessments rather than serve as independent diagnostic tools.

Keywords

Acute appendicitis , immature granulocyte , paediatric , perforated appendicitis

Ethical Statement

The study protocol was approved by Hitit University Faculty of Medicine Clinical Research Ethics Committee with the decision dated 31/01/2023 and numbered 2023/09.

References

• Morrow SE, Newman KD. Current management of appendicitis. Semin Pediatr Surg. 2007;16:34-40.
• Marzuillo P, Germani C, Krauss BS, Barbi E. Appendicitis in children less than five years old: a challenge for the general practitioner. World J Clin Pediatr. 2015;4:19-24
• Andersson MN, Andersson RE. Causes of short-term mortality after appendectomy: a population-based case-controlled study. Ann Surg. 2011;254:103-7.
• Kim DW, Suh CH, Yoon HM, et al. Visibility of normal appendix on CT, MRI, and sonography: a systematic review and meta-analysis. Am J Roentgenol. 2018; 211:W140-50.
• Pogorelić Z, Rak S, Mrklić I, Jurić I. Prospective validation of Alvarado value and Pediatric Appendicitis Value for the diagnosis of acute appendicitis in children. Pediatr Emerg Care. 2015;31:164-8.
• Maloney C, Edelman MC, Bolognese AC, et al. The impact of pathological criteria on pediatric negative appendectomy rate. J Pediatr Surg. 2019;54:1794-9.
• Zhao L, Feng S, Huang S, et al. Diagnostic value of hyperfibrinogenemia as a predictive factor for appendiceal perforation in acute appendicitis. ANZ J Surg. 2017;87:372-5.
• Anand S, Krishnan N, Birley JR, et al. Hyponatremia-a new diagnostic marker for complicated acute appendicitis in children: a systematic review and meta-analysis. Children (Basel). 2022;9:1070.
• Oztan MO, Aksoy GA, Ozdemir T, et al. Pentraxin-3: a strong novel biochemical marker for appendicitis in children. Am J Emerg Med. 2019;37:1912-6.
• Singh A, Pogorelić Z, Agrawal A, et al. Utility of ischemia-modified albumin as a biomarker for acute appendicitis: a systematic review and meta-analysis. J Clin Med. 2023;12:5486.
• Tintor G, Jukić M, Šupe-Domić D, et al. Diagnostic utility of serum leucine-rich α-2-glycoprotein 1 for acute appendicitis in children. J Clin Med. 2023;12:2455.
• Tintor G, Jukić M, Šupe-Domić D, et al. Diagnostic accuracy of leucine-rich α-2-glycoprotein 1 as a non-invasive salivary biomarker in pediatric appendicitis. Int J Mol Sci. 2023;24:6043.
• Pogorelić Z, Lukšić AM, Mihanović J, et al. Hyperbilirubinemia as an indicator of perforated acute appendicitis in pediatric population: a prospective study. Surg Infect (Larchmt). 2021;22:1064-71.
• Kakar M, Delorme M, Broks R, et al. Determining acute complicated and uncomplicated appendicitis using serum and urine biomarkers: interleukin-6 and neutrophil gelatinase-associated lipocalin. Pediatr Surg Int. 2020;36:629-36.
• Yazici M, Ozkisacik S, Oztan MO, Gürsoy H. Neutrophil/lymphocyte ratio in the diagnosis of childhood appendicitis. Turk J Pediatr. 2010;52:400-3
• Boshnak N, Boshnaq M, Elgohary H. Evaluation of platelet indices and red cell distribution width as newbiomarkers for the diagnosis of acute appendicitis. J Invest Surg. 2018;31:121-9.
• Noh H, Chang SJ, Han A. The diagnostic values of preoperative laboratory markers in children with complicated appendicitis. J Korean Surg Soc. 2012;83:237-41.
• Yu CW, Juan LI, Wu MH, et al. Systematic review and meta-analysis of the diagnostic accuracy of procalcitonin, C-reactive protein and white blood cell count for suspected acute appendicitis. Br J Surg. 2013;100:322-9.
• Fernandes B, Hamaguchi Y. Automated enumeration of immature granulocytes. Am J Clin Pathol. 2007;128:454-63.
• Unal Y. A new and early marker in the diagnosis of acute complicated appendicitis: immature granulocytes. Ulus Travma Acil Cerrahi Derg. 2018;24:434-9.
• Nierhaus A, Klatte S, Linssen 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.
• Yang HR, Wang YC, Chung PK, et al. Role of leukocyte count, neutrophil percentage, and C-reactive protein in the diagnosis of acute appendicitis in the elderly. Am Surg. 2005;71:344-7.
• Nissen M, Tröbs RB. The lymphocyte-to-monocyte ratio may distinguish complicated from non-complicated pediatric appendicitis: a retrospective study and literature review. Pediatr Neonatol. 2022;63:146-53.
• Grönroos JM. Do normal leucocyte count and C-reactive protein value exclude acute appendicitis in children?. Acta Paediatr. 2001;90:649-51.
• Prasetya D, Rochadi, Gunadi. Accuracy of neutrophil lymphocyte ratio for diagnosis of acute appendicitis in children: a diagnostic study. Ann Med Surg (Lond). 2019;48:35-8.
• Hajibandeh S, Hajibandeh S, Hobbs N, Mansour M. Neutrophil-to-lymphocyte ratio predicts acute appendicitis and distinguishes between complicated and uncomplicated appendicitis: a systematic review and meta-analysis. Am J Surg. 2020;219:154-63.
• Eun S, Ho IG, Bae GE, et al. Neutrophil-to-lymphocyte ratio for the diagnosis of pediatric acute appendicitis: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci. 2021;25:7097-107.
• Çelik B, Nalçacıoğlu H, Özçatal M, Torun YA. Role of neutrophil-to-lymphocyte ratio and platelet to-lymphocyte ratio in identifying complicated appendicitis in the pediatric emergency department. Ulus Travma Acil Cerrahi Derg. 2019;25:222-8.
• Doğan M, Gürleyen B. The role of immature granulocyte in the early prediction of acute perforated and nonperforated appendicitis in children. Ulus Travma Acil Cerrahi Derg. 2022;28:375-81.
• Anastasakis M, Trevlias I, Farmakis K, Valioulis I. The Importance of the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) as biomarkers for differentiating complicated and uncomplicated appendicitis. Diagnostics (Basel). 2024;14:2777.
• Krishnan N, Anand S, Pakkasjärvi N, et al. Mean platelet volume in the diagnosis of acute appendicitis in the pediatric population: a systematic review and meta-analysis. Diagnostics (Basel). 2022;12:1596.
• Blok GCGH, Nikkels ED, van der Lei J, et al. Added value of CRP to clinical features when assessing appendicitis in children. Eur J Gen Pract. 2022;28:95-101. Erratum in: Eur J Gen Pract. 2022;28:252.
• Karakaya D, Güngör T, Cakıcı EK, et al. Determining the effectiveness of the immature granulocyte percentage and systemic immune- inflammation index in predicting acute pyelonephritis. Postgrad Med. 2023;135:155-60.
• Ünal Y, Barlas AM. Role of increased immature granulocyte percentage in the early prediction of acute necrotizing pancreatitis. Ulus Travma Acil Cerrahi Derg. 2019; 25:177-82.
• Pavare JI, Gardovska D. Assessment of immature granulocytes percentage to predict severe bacterial infection in Latvian children: an analysis of secondary data. Medicina (Kaunas). 2018;54:56.
• Güngör A, Göktuğ A, Güneylioğlu MM, et al. Utility of biomarkers in predicting complicated appendicitis: can immature granulocyte percentage and C-reactive protein be used?. Postgrad Med. 2021;133:817-21.
• Kubat M, Şengül S. Value of neutrophil-to-platelet ratio, immature granulocyte-to-lymphocyte ratio, red blood cell distribution width-to-lymphocyte ratio in differentiating complicated acute appendicitis. Ulus Travma Acil Cerrahi Derg. 2022;28:607-14
• Güler Ö, Bozan MB, Alkan Baylan F, Öter S. The utility of immature granulocyte count and percentage on the prediction of acute appendicitis in the suspected acute appendicitis according to the alvarado scoring system: a retrospective cohort study. Turk J Gastroenterol. 2022;33:891-8.
• Mathews EK, Griffin RL, Mortellaro V, et al. Utility of immature granulocyte percentage in pediatric appendicitis. J Surg Res. 2014;190:230-4.
• Cesur İB, Özçelik Z, Matyar S, Ekberli G. Role of immature granulocyte count and percentage in the differential diagnosis of appendicitis. KSU journal. 2023;18:140-4.