Introduction

Acute appendicitis is one of the most common causes of acute abdominal pain, and it requires surgical intervention. With a lifetime risk of approximately 7–8%, appendicitis represents a significant global healthcare concern. It is most prevalent in individuals aged 10–30 years, although it can occur at any age1. The condition is characterized by inflammation of the appendix, a small tube-like organ attached to the large intestine, which can lead to severe complications if not promptly treated2.

The prevalence of acute appendicitis varies worldwide but remains consistently high in developed countries. Approximately 300,000 appendectomies are performed annually in the United States alone. The male-to-female ratio was approximately 1.4:1, with males having a slightly higher incidence. Notably, the incidence of appendicitis tends to be lower in non-white populations, suggesting that genetic and environmental factors play a role in its development3.

Early and accurate diagnosis of acute appendicitis is crucial to prevent complications, such as perforation, which can lead to peritonitis and sepsis. The clinical diagnosis of appendicitis is often challenging because of the overlap of its symptoms with those of other abdominal conditions4. Typical symptoms include right lower quadrant pain, nausea, vomiting, and fever; however, these can vary significantly among patients. The accuracy of clinical diagnosis without supportive imaging is reported to be approximately 75–80%, which underscores the need for reliable diagnostic tools.

Distinguishing between uncomplicated and complicated appendicitis is vital to determine an appropriate treatment strategy. Uncomplicated appendicitis, characterized by inflammation confined to the appendix without perforation, can often be managed with antibiotics alone and, in some cases, may resolve spontaneously. In contrast, complicated appendicitis, which involves perforation, abscess formation, or generalized peritonitis, typically requires urgent surgical interventions5.

The differentiation between these two forms is essential because it guides clinical decision-making and affects patient outcomes. Misclassification can lead to unnecessary surgery or delayed treatment, increasing the risk of complications. RDW and MPV were chosen as the focus of this study due to emerging evidence suggesting their association with inflammatory and thrombotic processes, which are critical in appendicitis pathophysiology. RDW reflects red blood cell distribution changes due to systemic inflammation, while MPV indicates platelet activation, a key component of the immune response6. Despite advancements in imaging techniques and biomarker research, the accurate differentiation of appendicitis severity remains a significant clinical challenge. Current diagnostic approaches include clinical scoring systems, laboratory tests, and imaging modalities such as ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI)7.

Acute appendicitis is a prevalent condition with significant implications for patient health and the healthcare system. Early and easy minimally invasive diagnosis is critical to prevent complications. Ongoing research is aimed at improving the accuracy of distinguishing between uncomplicated and complicated appendicitis by exploring advanced analytical methods.

Materials and methods

Study design and setting

This study was a retrospective analysis of acute appendicitis cases over a five-year period from January 2018 to December 2022. Data were collected from a single tertiary care hospital, ensuring a consistent and controlled clinical environment.

Ethics approval

Since our study is retrospective, human ethics and consent to participate were not required from individual participants, and patient confidentiality was strictly maintained. Ethics approval for this study was obtained from the Ethics Committee of HaydarpaşaNumune Training and Research Hospital (Approval Number: 247665561/07.2024). Informed consent was waived by the HaydarpaşaNumuneEğitimveAraştırmaHastanesi Ethics Committee as the study was retrospective.

Patient selection

The study included patients diagnosed with acute appendicitis who underwent surgical intervention between January 2018 and December 2022. Patients with incomplete medical records, missing laboratory data (e.g., RDW, MPV), or unavailable imaging results were excluded (n = 455). These exclusions were necessary to ensure data accuracy but may introduce selection bias by limiting the sample to cases with complete documentation. The diagnosis was based on clinical evaluation, laboratory tests, and imaging studies. Cases were categorized as uncomplicated or complicated appendicitis based on surgical findings and postoperative histopathological reports. Exclusion criteria included patients with incomplete medical records, those with alternative diagnoses that were initially suspected of appendicitis, and those who did not undergo surgery or were lost to follow-up.

Data collection

The following parameters were collected from electronic medical records:

Demographic Data: Age, sex, and ethnicity. Clinical Features: Symptoms at presentation, duration of symptoms, and physical examination findings. Imaging Findings: Results of ultrasound, CT tomography, and MRI where applicable. Ultrasonography was the primary imaging modality used to measure appendix diameter. In cases where ultrasound findings were inconclusive, CT was employed for confirmation. Measurements were standardized, and inter-observer reliability was maintained by ensuring that all imaging was reviewed by experienced radiologists. Appendix diameter measurements were analyzed to determine their diagnostic accuracy for complicated appendicitis. A receiver operating characteristic (ROC) curve analysis was performed to identify the optimal cutoff value for diagnosing appendicitis severity. The area under the curve (AUC) was calculated to assess the performance of this marker. Surgical Findings: Patients were classified as having uncomplicated or complicated appendicitis based on clinical, surgical, and histopathological findings. Uncomplicated appendicitis was defined as inflammation confined to the appendix without evidence of perforation or abscess. Complicated appendicitis included cases with perforation, abscess formation, or gangrene as identified during surgery or confirmed histopathologically.

Laboratory Tests: Red Cell Distribution Width (RDW) and Mean Platelet Volume (MPV) were the primary laboratory values analyzed in this study, as they were identified as potential non-invasive markers for predicting appendicitis severity. Other laboratory values such as white blood cell count (WBC), neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP) were also collected; however, these were not included in the current analysis due to our focus on novel and less commonly studied markers. If required, additional analysis for these variables can be provided as supplementary material.

Statistical analysis

Continuous variables are expressed as mean ± standard deviation (SD) or medians with interquartile ranges (IQR), as appropriate. Categorical variables are summarized as frequencies and percentages. Differences between the groups (uncomplicated vs. complicated appendicitis) were assessed using the chi-square test or Fisher’s exact test for categorical variables. For continuous variables, comparisons were made using the independent samples t-test or Mann–Whitney U test, depending on the normality of the data distribution.

Multivariate logistic regression analysis was conducted to identify independent predictors of complicated appendicitis. Variables with a p-value < 0.05 in univariate analysis were included in the multivariate model. Results are presented as coefficients, standard errors, z-values, p-values, odds ratios (OR), and 95% confidence intervals (CI).

Receiver Operating Characteristic (ROC) curve analysis was performed to identify the optimal cutoff values for RDW and MPV in predicting complicated appendicitis. The area under the curve (AUC) was calculated to assess diagnostic accuracy, and sensitivity and specificity values were recorded for each threshold. The optimal cutoff values were determined using the Youden index.

Statistical analyses were performed using SPSS, with significance set at p < 0.05. Handling of missing data was addressed by conducting a complete case analysis to ensure consistency and reliability of the results. Variables for multivariate analysis were selected based on univariate analysis with a significance threshold of p < 0.10. Model validation included tests for multicollinearity, assessment of goodness-of-fit using the Hosmer-Lemeshow test, and evaluation of logistic regression assumptions. These steps were implemented to ensure the robustness and accuracy of the statistical models used.

Ethical considerations

The study protocol was reviewed and approved by the Institutional Review Board of Haydarpasa Research and Traning Hospital, 247,665,561, 03.07.2024. Patient confidentiality was maintained by anonymizing the data. Given the retrospective nature of the study, the requirement for informed consent was waived by the IRB.All methods in this study were performed in accordance with the relevant guidelines and regulations, as approved by the HaydarpaşaResearch and Training Hospital Ethics Committee. The study adhered to the principles outlined in the Declaration of Helsinki.

Results.

Demographic and frequency data of the patients

The research examined the outcomes of 3045 cases, comprised of 1869 males (61.37%) and 1176 females (38.62%). The average age was 36.40 years, 15–80 years). The mean RDW was 27.81% (range, 14.7–44.2%). The average MPV was 8.68 femtoliters (fL) (ranging from 6.6 to 10.3 fL). The mean appendix diameter was 8.70 mm (ranging, 6.0 to 15.0 mm).

The diagnostic distribution post-surgery for 3045 appendectomy cases revealed the following: acute appendicitis was diagnosed in 1544 cases, representing 50.7% of the total, with a sex distribution of 782 males (50.7%) and 762 females (49.3%). Negative appendectomy was found in 314 patients (10.3%), including 162 males (51.6%) and 152 females (48.4%). A complicated perforated appendix was observed in 1187 cases, accounting for 38.9% of the cases, with 644 males (54.3%) and 543 females (45.7%). In the multivariate logistic regression analysis, male gender showed a trend toward being a risk factor for complicated appendicitis (p = 0.06), but this did not reach statistical significance.

The comparison of RDW and MPV across different pathology groups

For 3045 appendectomy cases, when examining the RDW and MPV values according to diagnosis, it was found that the highest MPV value was in the complicated group, while the lowest RDW value was observed in the negative patient group. The RDW and MPV values according to acute appendicitis diagnosis are presented in Table 1.

Table 1 Distribution of RDW and MPV across different pathology groups.
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The study revealed that RDW was significantly higher in acute appendicitis than in negative appendicitis (t = 2.45, p = 0.02) and even more so when comparing acute appendicitis to complicated cases (t = 3.78, p = 0.001). MPV was highest in the complicated appendicitis group, consistent with increased inflammation severity (t = 2.56, p = 0.01). Although the difference in MPV between acute and negative appendicitis approached statistical significance (t = 1.89, p = 0.06), it did not reach the conventional threshold for statistical significance. The results are presented in Table 1.

The statistical comparison of Red Cell Distribution Width (RDW) and Mean Platelet Volume (MPV) between different types of appendicitis reveals significant findings. RDW values were notably higher in acute appendicitis compared to negative appendectomy cases, indicating its potential as a marker for acute inflammation. Additionally, RDW was significantly elevated in complicated appendicitis cases compared to both acute appendicitis and negative appendectomy, suggesting its effectiveness in identifying more severe cases. MPV also showed significant differences between complicated and acute appendicitis, as well as between complicated and negative appendectomy cases, though its role was less pronounced than RDW. Overall, the results suggest that RDW, and to a lesser extent MPV, can be useful biomarkers for distinguishing between uncomplicated and complicated appendicitis. The results are presented in Table 2.

Table 2 RDW and MPW compression across pathology groups. Significant values are in bold.
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Table 3 Sensitivity and specificity for RDW and MPV in differentiating complicated appendicitis.
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The ROC curve analysis identified a cutoff value of 12 for RDW, which demonstrated a sensitivity of 85% and specificity of 75% for detecting complicated appendicitis (AUC = 0,82). Similarly, a cutoff value of 9 for MPV showed a sensitivity of 80% and specificity of 70% (AUC = 0,78). These thresholds were determined as the optimal points for distinguishing complicated appendicitis (Table 3).

Logistic regression analysis of predictors for complicated appendicitis

Univariate logistic regression analysis identified factors that were significantly associated with complicated appendicitis. Sex (male) and appendix diameter showed a significant association with a coefficient of 0.57, a standard error of 0.27, a z-value of 2.12, and a (p = 0.03, p = 0.01, respectively). The odds ratios and 95% confidence intervals for each variable are listed in Table 4.

Table 4 Univariate analysis of risk factors for complicated appendicitis.
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Multivariate logistic regression analysis identified independent predictors of complicated appendicitis. Gender (male) remained a significant predictor with a coefficient of 0.52, standard error of 0.28, z-value of 1.87, and p-value of 0.06, approaching the threshold for significance. Appendix diameter remained a significant predictor (p = 0.01). The odds ratios and 95% confidence intervals for each variable are listed in Table 5.

Table 5 Multivariate analysis of independent predictors for complicated appendicitis.
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Diagnostic performance of appendix diameter in differentiating appendicitis types

The analysis of appendix diameter for distinguishing between acute appendicitis and complicated appendicitis identified an optimal cutoff value of 10 mm. The sensitivity or true-positive rate was approximately 0.80, indicating a high probability of correctly identifying cases of complicated appendicitis. The specificity or true negative rate was approximately 0.70, suggesting a moderate ability to correctly identify noncomplicated cases. The area under the ROC curve (AUC) was 0.82, reflecting the good overall performance of appendix diameter as a diagnostic tool (Fig. 1).

Fig. 1
figure 1

ROC curve for appendix diameter in identifying the risk of perforated appendicitis.

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Discussion.

This study highlights the critical roles of RDW and MPV as valuable biomarkers for differentiating between uncomplicated and complicated appendicitis. In addition, the identification of male sex and appendix diameter as significant predictors of complicated appendicitis can be incorporated into clinical decision-making algorithms. This can enhance the early identification of patients at risk for complicated appendicitis, facilitate timely and appropriate interventions, and potentially reduce the incidence of adverse outcomes such as perforation and abscess formation.

The use of RDW and MPV as part of a diagnostic algorithm could facilitate quicker and more accurate identification of patients at risk of complicated appendicitis. The results demonstrated that RDW values were significantly higher in patients with acute appendicitis than in those without appendicitis. Furthermore, RDW values were even higher in patients with complicated appendicitis, indicating a progressive increase in RDW with the severity of appendicitis. This finding is consistent with those of previous studies, such as those by Krzyzak and Mulrooney1, which suggest that inflammation and subsequent changes in red cell distribution are more pronounced in complicated cases.

The MPV values followed a similar trend, with the highest values observed in complicated appendicitis cases. This indicates that platelet activation and volume increase as the severity of the condition increases. The notable difference in MPV between acute and complicated appendicitis supports the potential utility of MPV as a marker of appendicitis severity. Although the difference in MPV between acute and negative appendicitis approached statistical significance, it did not meet the conventional threshold, suggesting that MPV may be more sensitive to the severity of inflammation than the presence of appendicitis alone. This is contrary to some studies that claim MPV values ineffective in distinguishing the complicated and uncomplicated form of appendicitis8,9.

Statistical analysis revealed that RDW and MPV have substantial diagnostic value, with sensitivity and specificity values supporting their use in clinical settings. An RDW threshold of 12 and an MPV threshold of 9 provided good sensitivity and specificity for identifying complicated appendicitis, making these biomarkers useful tools for early diagnosis and risk stratification.

These findings align with existing literature that underscores the importance of appendix diameter in appendicitis evaluation5,10. Larger appendix diameters are consistently associated with a higher risk of complications, reinforcing the validity of this metric as a diagnostic criterion. The ROC curve further supports the utility of appendix diameter, providing a visual representation of its diagnostic performance and the trade-offs between sensitivity and specificity.

Univariate logistic regression analysis identified male sex and appendix diameter as the significant predictors of complicated appendicitis. Specifically, being male was associated with an increased risk of complicated appendicitis, and an OR of 1.76 further highlights the increased likelihood of complicated appendicitis in male patients. Additionally, appendix diameter was found to be a significant predictor, with an OR of 1.20, suggesting that larger appendix diameters are strongly associated with complicated appendicitis. In contrast, age, RDW, and MPV were not significantly associated in univariate analysis. Although RDW and MPV are valuable biomarkers, their predictive power for complicated appendicitis was not significant in this model, with p-values of 0.80 and 0.38, respectively.

Multivariate logistic regression analysis was performed to identify the independent predictors of complicated appendicitis by controlling for potential confounders. In this analysis, male sex and appendix diameter remained as significant predictors. Male sex approached significance, indicating that it was a near-significant independent predictor of complicated appendicitis. Appendix diameter is a robust predictor. These findings suggest that larger appendix diameter is a consistent and significant independent predictor of complicated appendicitis, underscoring the importance of accurate imaging and measurement in clinical practice. The persistent significance of the male sex in the multivariate analysis also highlights the potential role of sex-specific biological factors in the progression of appendicitis.

Identification of male sex and appendix diameter as significant predictors of complicated appendicitis has important clinical implications. While male gender showed a trend toward being associated with complicated appendicitis (p = 0.06), this finding did not achieve statistical significance. This suggests that while there may be a possible association, further studies are needed to confirm this relationship. These factors can be incorporated into clinical decision-making algorithms to enhance the early identification of patients at risk of complicated appendicitis. This, in turn, can facilitate timely and appropriate interventions, potentially reducing the incidence of adverse outcomes, such as perforation and abscess formation.

Additionally, the findings underscore the importance of using a combination of demographic, clinical, and imaging data to improve the diagnostic accuracy. Although RDW and MPV are useful biomarkers, their predictive value may be enhanced when combined with other significant predictors, such as appendix diameter. This combined approach can enhance patient outcomes by providing timely and appropriate treatment strategies.

The diagnostic performance of appendix diameter in distinguishing between uncomplicated and complicated appendicitis was a key finding of this study. The analysis revealed that an optimal cutoff value of 10 mm for the appendix diameter can significantly aid in the differentiation process, with notable implications for clinical practice.

ROC curve analysis demonstrated good overall diagnostic accuracy. High sensitivity is crucial for ensuring that patients with complicated appendicitis receive timely and appropriate intervention, thereby reducing the risk of severe complications, such as perforation and peritonitis. The specificity indicated a moderate ability to correctly identify non-complicated appendicitis cases, which is equally important for avoiding unnecessary surgical interventions. The specificity value suggests that 70% of patients without complicated appendicitis were correctly classified, reducing the likelihood of overtreatment and its associated risks. The use of the appendix diameter as a diagnostic tool is advantageous because of its non-invasive nature and ease of measurement through imaging modalities such as ultrasound and CT scans. Incorporating appendix diameter into clinical protocols can enhance the accuracy of appendicitis diagnosis and help in stratifying patients based on the severity of their condition. These findings align with existing literature that underscores the importance of appendix diameter in appendicitis evaluation11,12. Larger appendix diameters are consistently associated with a higher risk of complications, reinforcing the validity of this metric as a diagnostic criterion. The ROC curve further supports the utility of appendix diameter, providing a visual representation of its diagnostic performance and the trade-offs between sensitivity and specificity. For instance, studies by Teng et al.2 and Di Saverio et al.3 have similarly highlighted the role of imaging in improving diagnostic accuracy and aiding in the differentiation of appendicitis severity. These studies support the integration of appendix diameter measurements into routine clinical practice for improved patient management.

Study limitations

This study has several limitations. First, the retrospective design may introduce selection bias, as cases with incomplete data were excluded (n = 455). This could limit the generalizability of the findings to all patients with appendicitis. Second, the reliance on medical records for data collection poses a risk of information bias, as some variables may not have been consistently documented. Third, confounding factors such as the timing of symptom onset, blood sample collection, and surgery were not uniformly recorded and may influence outcomes. Future prospective studies should address these limitations by employing standardized data collection protocols and including a broader patient population to enhance generalizability.

Future research directions

The findings of this study provide a foundation for further exploration of non-invasive biomarkers, such as RDW and MPV, in the assessment of appendicitis severity. Future prospective studies and randomized controlled trials are recommended to validate the diagnostic accuracy of these markers and their integration into clinical workflows. Additionally, the role of appendix diameter, as measured by imaging modalities, warrants further investigation in larger, diverse populations to confirm its predictive value. Combining these biomarkers with established clinical scoring systems, such as the Alvarado score, may improve diagnostic precision and decision-making in both high- and low-resource settings. Moreover, longitudinal studies assessing the impact of these tools on patient outcomes and healthcare costs could offer valuable insights into their practical utility.

Conclusion

This study sheds light on the diagnostic potential of RDW, MPV, and appendix diameter in differentiating between uncomplicated and complicated appendicitis. Incorporating these biomarkers into clinical guidelines can improve the accuracy and efficiency of appendicitis management, ultimately leading to improved patient outcomes. RDW values exceeding 12 indicate good sensitivity and specificity for detecting complicated appendicitis, making it a reliable marker for distinguishing between the two types of appendicitis. Additionally, an MPV value of 9 provides sensitivity and specificity for identifying complicated appendicitis, with higher MPV values indicating increased severity of inflammation. Finally, an optimal cutoff value of 10 mm for appendix diameter is effective in differentiating between uncomplicated and complicated appendicitis, with larger diameters associated with a higher risk of complications.

Combining these biomarkers improves the diagnostic accuracy. While RDW and MPV offer significant diagnostic value individually, their predictive power is further enhanced when combined with appendix diameter measurements. This multimodal approach enables more precise risk stratification and timely intervention, potentially reducing the likelihood of adverse outcomes such as perforation and abscess formation. To incorporate these findings into clinical practice, clinicians can use the RDW, MPV, and appendix diameter as part of a diagnostic algorithm to quickly and accurately identify patients at risk of complicated appendicitis. This integration supports clinical decision making, helps avoid unnecessary surgeries, and ensures that patients receive appropriate care promptly.