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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 13  |  Issue : 1  |  Page : 33-36

Immature granulocytes: A novel biomarker of acute pericarditis


Department of Emergency Medicine, Health Science University, Antalya Training and Research Hospital, Antalya, Turkey

Date of Submission08-May-2021
Date of Decision22-Jul-2021
Date of Acceptance28-Sep-2021
Date of Web Publication19-Jan-2022

Correspondence Address:
Dr. Cihan Bedel
Health Science University Antalya Training and Research Hospital, Kazım Karabekir Street, Muratpaşa 07100, Antalya
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/injms.injms_60_21

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  Abstract 


Background: Cardiac enzymes and inflammatory biomarkers may be elevated in acute pericarditis (AP); however, there is no current biomarker specific for AP. Immature granulocyte (IG) has been used as a marker of inflammation in many diseases. Therefore, in this study, we aimed to investigate the clinical benefit of IG as a marker in the diagnosis of AP. Methodology: This retrospective study included study participants, who presented to our emergency department with chest pain, and were diagnosed with AP between 1 January 2019 and 1 January 2020. The hemogram and biochemistry parameters of all study participants, which were measured at the time of admission to the emergency department, were recorded. The parameters were compared between the patient and control groups. Results: The study included 32 study participants, who met the inclusion criteria, and 32 control study participants with similar demographic characteristics. The mean age of the study participants with AP was 32.19 ± 14.63 years. The study participants with AP had significantly higher IG values compared to the control group (0.47% ±0.24% vs. 0.26% ±0.1%; P < 0.001). High sensitivity (80%) and specificity (90.6%) were obtained for the prediction of AP at the cut-off value of IG >0.65 as the new parameter. Conclusion: IG, which can be obtained from a simple hemogram test, can be used as a marker for AP.

Keywords: Acute pericarditis, immature granulocyte, inflammation


How to cite this article:
Selvi F, Korkut M, Bedel C. Immature granulocytes: A novel biomarker of acute pericarditis. Indian J Med Spec 2022;13:33-6

How to cite this URL:
Selvi F, Korkut M, Bedel C. Immature granulocytes: A novel biomarker of acute pericarditis. Indian J Med Spec [serial online] 2022 [cited 2022 Dec 7];13:33-6. Available from: http://www.ijms.in/text.asp?2022/13/1/33/335970




  Introduction Top


Acute pericarditis (AP) accounts for approximately 5% of study participants admitted to the emergency department for chest pain, and it is the most common form of the pericardial disease.[1] AP varies significantly in terms of clinical symptoms, timing of symptoms, and prognosis and represents the low-risk conditions due to the treatment, compared to mortality-related diseases of chest pain such as aortic dissection and pneumonia.[2],[3] Pericarditis is diagnosed with electrocardiographic findings such as typical pleuritic chest pain, pericardiac friction sound, PR segment depression with widespread ST segment elevation, and pericardial effusion.[4],[5],[6] In addition, inflammatory markers such as pericardial inflammation and C-reactive protein (CRP and white blood cell [WBC] count) detected by imaging, and myocardial damage (creatine kinase, troponin) also supports the diagnosis; however, at present, there is no specific biomarker for AP.[7],[8]

Immature granulocytes (IG) in peripheral blood are an indicator of increased bone marrow activation and inflammation. They can be easily obtained from simple hemogram testing, especially with technical developments in recent years.[9] Recent studies have demonstrated that IG, as a marker of inflammation, could be a marker for mortality and the severity of sepsis, cardiovascular, and gastrointestinal system diseases.[10],[11],[12],[13] There are no studies in the literature demonstrating the efficacy of IG as a new inflammatory biomarker in the diagnosis of study participants with AP. Therefore, in this study, we aimed to investigate the clinical benefit of IG as a marker in the diagnosis of AP.


  Methodology Top


This retrospective study included study participants, who presented to our emergency department with chest pain, and was diagnosed with AP between 1 January 2019 and 1 January 2020. This study was approved by the Ethics Committee of our institution. The diagnosis of AP was made in the emergency medicine clinic with a cardiology consultation based on clinical symptoms, laboratory results, and typical radiological findings. The pericarditis that is associated with the myocarditis was considered as myo/pericarditis and included in the group with AP. The diagnosis of AP was made according to norms accepted by international guidelines due to the findings of retrosternal or precordial chest pain, pericardial auscultation, electrocardiography (ECG), pericardial effusion findings in echocardiography, and the laboratory findings supporting the diagnosis.[4],[5]

Study participants under 18 years of age, pregnant study participants, study participants with malignancy, hematological disorders, and insufficient data were excluded from the study. The vital signs, hemogram, and biochemistry parameters of all study participants, which were measured at the time of admission to the emergency department, were recorded. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) measurements were recorded among the vital signs. In the hemogram, hemoglobin, WBC, platelet, neutrophil, lymphocyte, and IG levels were recorded. CRP and glucose, which were examined in the emergency room from biochemistry examinations, were recorded as the biochemistry tests, and the high-density lipoprotein, low-density lipoprotein, and the triglyceride results were recorded as the biochemistry tests that were performed within the 24 h of the first admission. IG measurement was performed by automated whole blood analyzer with Sysmex XN-1000 (Sysmex Corp., Kobe, Japan). Among the study participants that were screened retrospectively, the study participants with similar sociodemographic characteristics, who were admitted to the emergency department with nonspecific chest pain and who were not diagnosed with acute coronary syndrome or AP, who did not have a medical history of AP, did not use medication nor having a specific chronic disease, were randomized in a similar number to create the control group. The parameters were compared between the patient and control groups.

Statistical analysis of all variables was performed using SPSS 21.0 software package (version 21.0, SPSS Inc., Chicago, IL, USA). Continuous variables were presented as mean ± standard deviation, and the categorical data were presented as frequency and percentage (%). Independent t-test and Mann–Whitney U test were used for comparing the parameters according to their distributions. In addition, categorical data were evaluated with the Chi-square test. The receiver operating characteristic (ROC) analysis was performed to determine the success of WBC, CRP, and IG as the markers for the diagnosis of AP. A P < 0.05 was considered statistically significant.


  Results Top


The study included 32 study participants, who met the inclusion criteria, and 32 control study participants with similar demographic characteristics. The AP group consisted of 29 males (90.6%) and 3 females (9.4%), and the control group consisted of 28 males (87.5%) and 4 females (12.5%). The mean age of the study participants with AP was 32.19 ± 14.63 years, and the mean age was 33.06 ± 14.28 in the control group. When the mean ages of the patient and control groups were compared, there was no statistically significant difference (P = 0.444). The mean SBP value of the study participants was 125.33 ± 21.47 mmHg, the mean DBP value was 78.89 ± 13.68 mmHg, and the HR value was calculated as 90.39 ± 13.47 bpm. While hypertension, coronary heart disease, and hyperlipidemia were the most common risk factors, antiplatelets, statins, and antihypertensive drugs were the drugs that were most frequently used by the study participants. When the patient and control groups were compared according to laboratory parameters, the study participants with AP had significantly higher WBC values (10.46 ± 2.64 × 103/mm3 vs. 9.21 ± 2.33 × 103/mm3; P = 0.045), higher neutrophil counts (7.13 ± 2.34 × 103/mm3 vs. 5.68 ± 2.19 × 103/mm3 vs.; P = 0.008), higher CRP values (67(94) mg/L vs. 2[4] mg/L; P < 0.001), higher troponin values (400.21 ± 87.82 ng\L vs. 4.21 ± 2.44 ng\L; P < 0.001), and higher IG values (0.47% ± 0.24% vs. 0.26% ± 0.11%; P < 0.001) [Figure 1]. The demographic characteristics and laboratory values of the patient and control groups are presented in [Table 1] and [Table 2]. No complications were observed in the follow-up of the patients.
Figure 1: Comparison of ımmature granulocytes between acute pericarditis and control study participants

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Table 1: Demographic characteristics of study participants with acute pericarditis

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Table 2: Comparison of patient and control groups according to age, gender, and laboratory data

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We investigated the effectiveness of WBC, troponin, CRP, and IG in the prediction of AP using the ROC analysis. The area under the curve (AUC) values of these variables were found to be statistically significant for predicting AP [Figure 2]. Troponin had the highest AUC (0.953; P < 0.001), followed by CRP, IG, and WBC (AUC = 0.943, 0.801, and 0.667). High sensitivity (80%) and specificity (90.6%) were obtained for the prediction of AP at the cut-off value of IG >0.65 as the new parameter [Table 3].
Figure 2: Receiver operating characteristic curve analysis of the parameters in the diagnosis of acute pericarditis

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Table 3: Effectiveness of the parameters in the diagnosis of acute pericarditis

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  Discussion Top


AP is a pericardial disease that can occur with a wide range of conditions ranging from an asymptomatic condition to chest pain similar to infarction and life-threatening cardiovascular conduction disorder. Acute complications and recurrence can be prevented with early diagnosis and treatment.[14] Many inflammatory markers such as cardiac-specific troponin I or T, WBC, CRP, and sedimentation can be elevated in AP; however, there is no current biomarker specific to the disease.[15],[16] Our results demonstrated that IG is a simple, easily accessible parameter that can be used to predict the diagnosis of AP.

In their study, Maisch et al. demonstrated that viral or bacterial infections were common agents for AP.[17] In addition, the cases of pericarditis due to cardiac surgery, pacemaker implantation, ablation, and percutaneous coronary intervention have been reported in recent years.[18] In internationally accepted guidelines, the diagnosis of AP is basically suggested in the presence of at least two of the 4 findings such as chest pain, pericardial friction sound, ECG abnormality, and pericardial effusion, which are typically pleuritic and vary according to position.[4],[5] In addition, the elevation of inflammatory markers and cardiac markers such as increased CRP, sedimentation and WBC, and imaging methods can help diagnose and monitor disease activity.[19] In our study, similar to the literature, we found a significant relationship between high WBC, CRP, and troponin and AP.

Studies have shown that biomarkers are needed in AP due to their fast, simple applicability, easy measurement, and affordable cost in clinical practice.[20] In the recent years, there have been many studies on IG measuring the number of promyelocytes, myelocytes, and metamyelocytes in peripheral blood.[21] With this parameter, which can be obtained from a simple hemogram examination, IG can be measured. Thus, it can be used in the examination and follow-up of many diseases.[10] In a study conducted by Hampson et al., it was reported to be a useful and potential marker in the diagnosis of sepsis in study participants with IG and severe burns.[22] In a study conducted by Lima et al., IG% >1.35 was proven to be useful in screening infection in the intensive care study participants with 44.6% sensitivity and 64.4% specificity. In a recent study by Huang et al., it was demonstrated that the increased IG values could indicate the severity of disease in study participants with acute pancreatitis.[23] In another study, it was reported that there was a significant relationship between increasing IG values and the severity of coronary artery disease.[12] In yet another study, it was emphasized that the increased IG values were one of the markers of mortality in study participants with bleeding in the upper gastrointestinal system.[10]

To the best of our knowledge, there are no studies in the literature that examined the relationship between the IG value and AP. In our study, we found significantly higher IG values in patients with AP. IG > 0.65 had high levels of sensitivity and specificity as the new parameter for the severity of AP.

Our study had some limitations. The first is that our study was retrospectively designed and performed with relatively small number of study participants. This low number may be due to the rarity of the disease and the short duration of the patient screening since the IG value in the hemogram parameter could not be checked before 2018. Another limitation of ours is that the time from the onset of the symptom to the exact sample collection is not known clearly. In addition, IG values were measured at the time of admission and could not be measured regularly. An important limitation of ours is that the levels of the parameters in AP etiological differences could not be compared. Multicenter prospective studies with a larger patient population are needed to better analyze the data in our study and to demonstrate the usability of the IG parameter in the diagnosis of AP.


  Conclusion Top


IG, which can be obtained from a simple hemogram test, can be used as a marker for AP.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Meireles AC, Oliveira JV, Pontes BD, Souza AC, Gomes LC, Silva TE, et al. Development of diagnostic score for acute pericarditis in patients admitted for chest pain. MedRxiv 2020 https://doi.org/10.1101/2020.08.19.20176750.  Back to cited text no. 1
    
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Lazaros G, Antonopoulos AS, Lazarou E, Vlachopoulos C, Vogiatzi G, Vassilopoulos D, et al. Age- and sex-based differences in patients with acute pericarditis. Eur J Clin Invest 2021;51:e13392.  Back to cited text no. 3
    
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Adler Y, Charron P, Imazio M, Badano L, Baron-Esquivias G, Bogaert J, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases. Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC). G Ital Cardiol (Rome) 2015;16:702-38.  Back to cited text no. 4
    
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Adler Y, Charron P, Imazio M, Badano L, Barón-Esquivias G, Bogaert J, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC) Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2015;36:2921-64.  Back to cited text no. 5
    
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Assayag M, Abbas R, Chanson N, Perozziello A, Ducrocq G, Alexandra JF, et al. Diagnosis of systemic inflammatory diseases among patients admitted for acute pericarditis with pericardial effusion. J Cardiovasc Med (Hagerstown) 2017;18:875-80.  Back to cited text no. 6
    
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Imazio M, Spodick DH, Brucato A, Trinchero R, Markel G, Adler Y. Diagnostic issues in the clinical management of pericarditis. Int J Clin Pract 2010;64:1384-92.  Back to cited text no. 7
    
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Ismail TF. Acute pericarditis: Update on diagnosis and management. Clin Med (Lond) 2020;20:48-51.  Back to cited text no. 8
    
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Mare TA, Treacher DF, Shankar-Hari M, Beale R, Lewis SM, Chambers DJ, et al. The diagnostic and prognostic significance of monitoring blood levels of immature neutrophils in patients with systemic inflammation. Crit Care 2015;19:57.  Back to cited text no. 9
    
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Bedel C, Korkut M, Avcı A, Uzun A. Immature granulocyte count and percentage as new predictors of mortality in patients with upper gastrointestinal bleeding. Indian J Crit Care Med 2020;24:794-8.  Back to cited text no. 10
    
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Korkut M, Bedel C, Selvi F. Are immature granulocytes and derivatives early predictors of acute appendicitis and acute complicated appendicitis in adults? Formos J Surg 2020;53:123-7.  Back to cited text no. 11
  [Full text]  
12.
Bedel C, Korkut M, Aksoy F, Kuş G. Usefulness of ımmature granulocytes to predict high coronary SYNTAX score in acute coronary syndrome; a cross-sectional study. Arch Acad Emerg Med 2020;8:e73.  Back to cited text no. 12
    
13.
Sinaga RH, Utariani A, Wardhani P, Hardiono H. Immature granulocyte and mean platelet volume as a predictor of 30-day postoperative mortality in patients with sepsis caused by peritonitis. Bali J Anaesthesiol 2020;4:166-71.  Back to cited text no. 13
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14.
Sinagra G, Anzini M, Pereira NL, Bussani R, Finocchiaro G, Bartunek J, et al. Myocarditis in clinical practice. Mayo Clin Proc 2016;91:1256-66.  Back to cited text no. 14
    
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Imazio M, Brucato A, Barbieri A, Ferroni F, Maestroni S, Ligabue G, et al. Good prognosis for pericarditis with and without myocardial involvement: Results from a multicenter, prospective cohort study. Circulation 2013;128:42-9.  Back to cited text no. 15
    
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Long B, Long DA, Tannenbaum L, Koyfman A. An emergency medicine approach to troponin elevation due to causes other than occlusion myocardial infarction. Am J Emerg Med 2020;38:998-1006.  Back to cited text no. 16
    
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Maisch B, Rupp H, Ristic A, Pankuweit S. Pericardioscopy and epi- and pericardial biopsy – A new window to the heart improving etiological diagnoses and permitting targeted intrapericardial therapy. Heart Fail Rev 2013;18:317-28.  Back to cited text no. 17
    
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Gouriet F, Levy PY, Casalta JP, Zandotti C, Collart F, Lepidi H, et al. Etiology of pericarditis in a prospective cohort of 1162 cases. Am J Med 2015;128:784.e1-8.  Back to cited text no. 18
    
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Chiabrando JG, Bonaventura A, Vecchié A, Wohlford GF, Mauro AG, Jordan JH, et al. Management of acute and recurrent pericarditis: JACC state-of-the-art review. J Am Coll Cardiol 2020;75:76-92.  Back to cited text no. 19
    
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Ala CK, Banerjee K, Chahine J, Verma B, Kumar A, Furqan M, et al. D-dimer as a novel marker of inflammation in pericarditis. J Am Coll Cardiol 2019;73:984.  Back to cited text no. 20
    
21.
Karon BS, Tolan NV, Wockenfus AM, Block DR, Baumann NA, Bryant SC, et al. Evaluation of lactate, white blood cell count, neutrophil count, procalcitonin and immature granulocyte count as biomarkers for sepsis in emergency department patients. Clin Biochem 2017;50:956-8.  Back to cited text no. 21
    
22.
Hampson P, Dinsdale RJ, Wearn CM, Bamford AL, Bishop JR, Hazeldine J, et al. Neutrophil dysfunction, ımmature granulocytes, and cell-free DNA are early biomarkers of sepsis in burn-injured patients: A prospective observational cohort study. Ann Surg 2017;265:1241-9.  Back to cited text no. 22
    
23.
Huang Y, Xiao J, Cai T, Yang L, Shi F, Wang Y, et al. Immature granulocytes: A novel biomarker of acute respiratory distress syndrome in patients with acute pancreatitis. J Crit Care 2019;50:303-8.  Back to cited text no. 23
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3]



 

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