Original Contribution
Diagnostic accuracy of fibrinogen to differentiate appendicitis from nonspecific abdominal pain in children

https://doi.org/10.1016/j.ajem.2016.10.003Get rights and content

Abstract

Aim

The aim of this study was to assess the diagnostic accuracy of the biomarker fibrinogen (FB), along with the more traditional markers white blood cell count (WBC), absolute neutrophil count (ANC), and C-reactive protein (CRP), to discriminate appendicitis from nonspecific abdominal pain (NSAP) in children.

Methods

We prospectively evaluated all children aged 5 to 15 years admitted for suspected appendicitis at an academic pediatric emergency department during 2 years. Diagnostic accuracy of FB (prothrombin time–derived method), WBC, ANC, and CRP was assessed by the area under the curve (AUC) of the receiver operating characteristic curve.

Results

A total of 275 patients were enrolled in the study (143 NSAP, 100 uncomplicated appendicitis, and 32 complicated appendicitis). WBC and ANC had a moderate diagnostic accuracy for appendicitis vs NSAP (WBC: AUC 0.79, ANC: AUC 0.79). FB and CPR had a poor diagnostic accuracy for appendicitis vs NSAP (FB: AUC 0.63, CRP: AUC 0.64) and a good diagnostic accuracy for complicated vs uncomplicated appendicitis (FB: AUC 0.86, CRP: AUC 0.90). All inflammatory markers had a good diagnostic accuracy for complicated appendicitis vs NSAP.

Conclusions

WBC and ANC are useful inflammatory markers to discriminate appendicitis from NSAP. FB and CRP are not very useful to discriminate appendicitis from NSAP, but they discriminate properly complicated from uncomplicated appendicitis and NSAP, with a similar diagnostic accuracy. In a child with suspected appendicitis, a plasma FB level (prothrombin time–derived method) >520 mg/dL is associated to an increased likelihood of complicated appendicitis.

Introduction

Appendicitis is the most common acute surgical condition of the abdomen in children. It is diagnosed in up to 10% of children presenting with acute abdominal pain at the emergency department [1]. A compatible clinical history and physical examination remain the cornerstone of diagnosis. Other diagnostic tools such as inflammatory markers, imaging studies including ultrasonography (US) and computed tomography, and clinical prediction rules and protocols significantly help in the diagnostic process, increasing both efficiency and accuracy [2]. Despite all these diagnostic advances, initial evaluation misdiagnosis rates in children can reach up to 30% mainly because of the variable and nonspecific presentation of the disease and the wide differential diagnosis of abdominal pain in children. Misdiagnosis is associated with high rates of perforation (12%-38%), leading to significant morbidity and negative appendectomy (2%-30%) [3], [4].

Diagnostic accuracy of inflammatory markers to discriminate appendicitis is limited because they are increased in many abdominal pain disorders [2]. White blood cell count (WBC), absolute neutrophil count (ANC), and C-reactive protein (CRP) are the most studied and used in clinical practice. Other potential markers of appendicitis have been evaluated, such as procalcitonin [5], bilirubin [6], calprotectin [7], or interlekin-6 [8], but for now have not been found any more useful [9]. Fibrinogen (FB) has been reported recently as a useful biomarker in the diagnosis of appendicitis because it is an important inflammatory modulator [10], [11].

Because nonspecific abdominal pain (NSAP) is the most common diagnosis on discharge following admission for abdominal pain in childhood and it is the most common process that requires differential diagnosis with appendicitis in clinical practice [12], [13], [14], we compare inflammatory markers only in these groups of patients.

The aim of this prospective study was to assess the diagnostic accuracy of the biomarker FB, along with the more traditional inflammatory markers WBC, ANC, and CRP, to differentiate appendicitis from NSAP in children.

Section snippets

Methods

This prospective, observational study was conducted at a tertiary academic pediatric emergency department (University Hospital of Vigo, Spain), enrolling subjects aged 5 to 15 years admitted for suspected appendicitis between January 1, 2013, and December 31, 2014. We selected cases of NSAP and appendicitis according to inclusion and exclusion criteria. Inclusion criteria were clinical suspicion of appendicitis; laboratory studies including WBC, ANC, CRP, and FB (prothrombin time–derived

Results

During the study period, 764 patients were evaluated for suspected appendicitis. NSAP and appendicitis were the most frequent diagnosis with 327 (42%) and 273 (36%) cases, respectively (Table 1). Following the inclusion and exclusion criteria, 275 patients were enrolled in the study composed of 143 NSAP and 132 appendicitis cases; there were 100 cases of uncomplicated appendicitis (suppurative appendicitis) and 32 cases of complicated appendicitis (9 gangrenous and 23 perforated appendicitis).

Discussion

The term NSAP refers to abdominal pain for which organic pathology is not the cause suspected by the attending medical professional [13]. It is a diagnosis of exclusion, identifying a nonspecific syndrome that is self-limiting and does not recur [12]. NSAP is a safe diagnosis in pediatric population because only 1.6%-5.8% of cases will be diagnosed of a specific disease and the risk of missing appendicitis is low. Nevertheless, NSAP is the most common diagnosis on discharge following admission

Limitations

Limitations of this study include the following: (a) Histopathological examination of the appendix, considered the reference standard for appendicitis diagnosis, is not available for patients with NSAP (partial verification bias or workup bias) [34], [35]. Nonoperated patients, who did not develop appendicitis during follow-up, were assumed to be cases without disease, but epidemiological and clinical imaging studies have shown that spontaneous resolution of disease is possible [36]; therefore,

Conclusions

WBC and ANC are useful inflammatory markers to discriminate appendicitis from NSAP, but they do not discriminate properly complicated from uncomplicated appendicitis. FB and CRP are not very useful to discriminate appendicitis from NSAP, but they discriminate properly complicated from uncomplicated appendicitis and NSAP, with a similar diagnostic accuracy. In a child with suspected appendicitis, a plasma FB level (prothrombin time–derived method) >520 mg/dL is associated with an increased

Conflict of interest

The authors declare that they have no conflict of interest.

Author declaration

All authors have seen and approved the final version of the manuscript being submitted, and they warrant that the article is the authors' original work, has not received prior publication, and is not under consideration for publication elsewhere.

References (36)

  • C.W. Yu 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)
  • K. Atahan et al.

    Preoperative diagnostic role of hyperbilirubinaemia as a marker of appendix perforation

    J Int Med Res

    (2011)
  • B. Makay et al.

    Can we use faecal calprotectin to distinguish abdominal pain of familial Mediterranean fever (FMF) from acute appendicitis?

    Clin Rheumatol

    (2009)
  • İ. Ozguner et al.

    Are neutrophil CD64 expression and interleukin-6 early useful markers for diagnosis of acute appendicitis?

    Eur J Pediatr Surg

    (2014)
  • D.H. Schellekens et al.

    Evaluation of the diagnostic accuracy of plasma markers for early diagnosis in patients suspected for acute appendicitis

    Acad Emerg Med

    (2013)
  • J. Li et al.

    Alterations of the preoperative coagulation profile in patients with acute appendicitis

    Clin Chem Lab Med

    (2011)
  • O. Menteş et al.

    The value of serum fibrinogen level in the diagnosis of acute appendicitis

    Ulus Travma Acil Cerrahi Derg

    (2012)
  • P.A. Barker et al.

    Hospital re-admission in children with non-specific abdominal pain

    Pediatr Surg Int

    (2002)
  • Cited by (26)

    • Fibrinogen as a Marker of Overall and Complicated Acute Appendicitis: A Systematic Review and Meta-Analysis

      2022, Journal of Surgical Research
      Citation Excerpt :

      As shown in Figure 1 of the workflow, 22 of the 104 publications identified from the initial literature search were retrieved for a full-text review. Ten articles7-16 were included in our final analysis. The use of FB in the diagnosis of overall appendicitis was reported in seven research,7,8,12-16 and eight studies were included in the comparison of uncomplicated versus complicated appendicitis; 1386 patients had uncomplicated appendicitis and 602 patients had complicated appendicitis.

    • Evaluation of plasma level of fibrinogen as a diagnostic criterion in acute appendicitis; cohort study

      2022, Annals of Medicine and Surgery
      Citation Excerpt :

      Following 6–12 h from inflammation initiation plasma level of CRP reaches to the point that is detectable [5]. Although the higher plasma level of measured CRP implied on the more severe inflammatory process and even complicated appendicitis, the marker was not enough whether sensitive or specific for early diagnosis of AA [6–8]. Plasma fibrinogen is of another confirmed acute phase reactant agent that is originally synthesized in hepatocytes and acts primarily in hemostasis, and inflammatory response following infective or traumatic stress.

    • Appendicitis and related abdominal pain

      2021, Features and Assessments of Pain, Anesthesia, and Analgesia
    • The diagnostic value of hepcidin to predict the presence and severity of appendicitis in children

      2018, Journal of Surgical Research
      Citation Excerpt :

      Since standard laboratory parameters also seem to be relatively unreliable, ongoing research is performed in search for other, more reliable laboratory parameters. Consequently, a variety of markers like fibrinogen, bilirubin, calprotectin, and serum amyloid A have been addressed in the literature.15,28,29 However, serum values of hepcidin have not yet been examined in a pediatric appendicitis cohort.

    View all citing articles on Scopus

    Funding source declaration: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

    View full text