Evaluation of the relationship between ABO and Rh blood groups and clinical course in acute pancreatitis: A retrospective observational cohort study.

This study demonstrates a potential association between ABO blood groups and the severity of AP. Notably, patients with blood group O exhibited a significantly higher rate of moderate-to-severe disease compared to other groups, suggesting that this blood group may not always confer a protective effect. This observation implies that factors such as disease etiology, genetic background, and individual inflammatory responses may play pivotal roles in shaping clinical outcomes. Furthermore, male sex, obesity, and elevated C-reactive protein (CRP) levels were significantly associated with increased disease severity. The study suggests the potential utility of combining fixed biological markers – such as ABO blood group – with dynamic biochemical indicators to enhance early risk stratification in patients with AP. While the literature has rarely addressed this particular association, our findings highlight a biologically plausible pattern whereby blood group O may, under certain conditions, correlate with worse clinical trajectories. To further elucidate the prognostic role of ABO blood groups in pancreatitis, large-scale, multicenter prospective studies – stratified by etiological subtypes and regional characteristics – are warranted. Incorporating ABO typing into early assessment protocols – alongside inflammatory markers – may enhance clinical decision-making in AP, especially in resource-limited settings.

Acute pancreatitis (AP) is a sudden-onset inflammatory disease of the pancreas. While the majority of cases follow a benign and self-limiting course, some patients may develop severe clinical conditions that can progress to multi-organ failure. [ 1 ] Therefore, accurate early prediction of disease severity and rapid identification of high-risk patients are critical for successful treatment outcomes. [ 2 ] Currently, risk stratification methods rely on various clinical scoring systems (e.g., Ranson, APACHE-II) and inflammatory markers such as C-reactive protein (CRP) and procalcitonin. However, these approaches have certain limitations in terms of reliability and practical applicability. [ 3 , 4 ] This has led to a growing need for more dependable and easily accessible prognostic indicators in AP. ABO and Rh blood group antigens are not only important for transfusion compatibility but have also been associated with a range of clinical conditions, including thromboembolic events, susceptibility to infections, and certain malignancies. [ 5 , 6 ] These associations are thought to be mediated by the expression of antigens on cell surfaces, their effects on microcirculation, and their involvement in inflammatory responses. [ 7 , 8 ] In this context, it has been suggested that ABO blood groups may influence the severity of AP. However, the results of published studies on this topic remain inconsistent. [ 9 - 12 ] Therefore, investigating the potential role of ABO and Rh systems in the prognosis of AP is important not only to improve our understanding of underlying biological mechanisms but also to support clinical decision-making processes. The aim of this study was to evaluate the relationship between ABO and Rh blood groups and disease severity and clinical outcomes in patients with AP, and to determine whether these fixed biological markers offer prognostic value when considered alongside other clinical risk factors.

Conceptualization: Suat Evirgen, Sirin Cetin, Yavuz Pirhan, Onder Karabay. Data curation: Suat Evirgen. Investigation: Yavuz Pirhan. Methodology: Sirin Cetin. Project administration: Suat Evirgen, Meryem Cetin. Validation: Sirin Cetin, Yasin Duran. Visualization: Sirin Cetin, Meryem Cetin. Resources: Meryem Cetin. Software: Meryem Cetin. Supervision: Meryem Cetin. Writing – original draft: Suat Evirgen, Sirin Cetin, Meryem Cetin. Writing – review & editing: Sirin Cetin, Meryem Cetin.

This study was designed as a retrospective observational cohort study and was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the Ethics Committee of Amasya University Faculty of Medicine (Approval No: 288979, October 2, 2025). Patient confidentiality was strictly maintained throughout the study, and all data were analyzed anonymously. Data extraction and analysis were initiated only after ethics committee approval was obtained. Because of the retrospective design of the study and the use of anonymized patient data, the requirement for individual informed consent was waived by the ethics committee. Patients aged 18 years and older who were admitted to the Emergency Department of Amasya University Şerefeddin Sabuncuoğlu Training and Research Hospital between January 2018 and May 2025 with a diagnosis of AP were retrospectively included. A confirmed diagnosis of AP based on clinical, biochemical, and/or radiological criteria according to the Revised Atlanta Classification. Age ≥ 18 years. Complete laboratory, imaging, and hospitalization records. Recorded ABO and Rh blood group data in the hospital information system. No history of other systemic inflammatory diseases at the time of admission. History of chronic pancreatitis, pancreatic cancer, pancreatic surgery, or pancreatic cyst/pseudocyst. Patients under 18 years of age and pregnant individuals. Coexisting severe comorbidities such as acute hepatitis, cholangitis, malignancy, sepsis, or immunodeficiency. Incomplete laboratory, imaging, or blood group data. Patients managed on an outpatient basis without hospitalization. The diagnosis of AP was established if at least 2 of the following three findings were present according to the Revised Atlanta Classification: Sudden onset of upper abdominal pain consistent with AP. Serum amylase and/or lipase levels ≥3 times the upper limit of normal. Imaging findings (contrast-enhanced abdominal CT, MRI, or transabdominal US) characteristic of AP. Data were retrieved retrospectively using the Hospital Information Management System and electronic medical records. All variables were recorded into a standardized data collection form. The collected data were categorized as follows: Demographic variables: age, sex, body mass index, smoking and alcohol use history. Clinical characteristics: symptom duration at admission, etiology (biliary, alcohol, hypertriglyceridemia, hypercalcemia, drug-induced, idiopathic), and initial laboratory values (leukocyte count, hematocrit, amylase, lipase, CRP, BUN, creatinine, calcium, ALT). Blood group information: ABO and Rh blood group data were obtained from the hospital blood bank records. Clinical outcomes: Length of hospital stay, need for intensive care unit admission, local complications (pseudocyst, pancreatic necrosis, fluid collection), systemic complications (organ failure), and mortality. To address potential sources of bias, we applied prespecified eligibility criteria and used standardized definitions for outcomes and disease severity based on the Revised Atlanta Classification. Data were extracted from the hospital information system using a standardized data collection form, and ABO/Rh blood group information was obtained from blood bank records. A complete-case approach was used; records with incomplete laboratory, imaging, or blood group data were excluded, and no missing values remained for variables included in the final analyses. Disease severity was classified based on the Revised Atlanta Classification: Mild acute pancreatitis: self-limiting disease without local/systemic complications or organ failure. Moderately severe acute pancreatitis: transient organ failure lasting 248 hours and/or local or systemic complications. Severe acute pancreatitis: persistent organ failure lasting longer than 48 hours. Accordingly, the primary outcome of this study was defined as “non-mild AP,” encompassing both moderately severe and severe forms. Data analysis was performed using IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk). The distribution of continuous variables was assessed using the Shapiro–Wilk test. Normally distributed variables were presented as mean ± standard deviation, while non-normally distributed variables were summarized as median (interquartile range, IQR). Comparisons between 2 groups were conducted using Student t test or the Mann–Whitney U test for continuous variables, and the chi-square test or Fisher exact test for categorical variables, as appropriate. A P -value < .05 was considered statistically significant for all analyses. Records with incomplete key data were excluded (complete-case analysis). To further evaluate the relationship between inflammatory burden and blood group status, CRP levels were compared across ABO blood groups and between O and non-O groups. Because ABO blood group is a categorical variable, group-based comparisons were performed. The Kruskal–Wallis test was used to compare CRP levels across ABO blood groups, and the Mann–Whitney U test was used to compare CRP levels between O and non-O groups. In addition, the association between O-group status and CRP levels was assessed using Spearman correlation analysis. Visual figures were prepared to illustrate CRP distributions according to blood group categories and the correlation coefficient.

A total of 612 patients who were hospitalized with a diagnosis of AP at Amasya University Şerefeddin Sabuncuoğlu Training and Research Hospital between January 2018 and May 2025 were retrospectively reviewed. After applying inclusion and exclusion criteria, 100 patients were excluded, and the final analysis was conducted on 512 patients. All variables included in the analyses were complete for these 512 patients. The median age of the study population was 54 years (IQR: 41–67). Of the patients, 52.3% were female (n = 268) and 47.7% were male (n = 244). The mean body mass index was 28.4 ± 4.7 kg/m 2 . The most common etiology of AP was biliary in origin (72.2%). Other causes included idiopathic (20.3%), alcohol-related (4.3%), and hypertriglyceridemia (3.2%). Regarding ABO blood group distribution, 219 patients (42.8%) had blood group A, 87 patients (16.9%) had blood group B, 35 patients (6.9%) had blood group AB, and 171 patients (33.4%) had blood group O. Rh positivity was observed in 450 patients (87.9%), whereas Rh negativity was observed in 62 patients (12.1%). These findings are summarized in Table 1 . Demographic and clinical characteristics of the study population. AP = acute pancreatitis, BMI =body mass index, Rh = rhesus factor. Among patients with blood group A, 34 of 219 patients (15.5%) had non-mild AP. The corresponding rates were 11 of 87 patients (12.6%) in blood group B, 4 of 35 patients (11.4%) in blood group AB, and 42 of 171 patients (24.5%) in blood group O. The higher rate of non-mild AP observed among patients with blood group O was statistically significant compared with the other ABO blood groups ( P  = .033). No significant difference was observed in the frequency of non-mild pancreatitis between Rh-positive and Rh-negative patients (18.1% vs 16.1%; P  = .88). The distribution of disease severity by ABO and Rh blood groups is presented in Table 2 . Comparison of acute pancreatitis severity by ABO and Rh blood groups. ABO = ABO blood group system, Rh = rhesus factor. When analyzing clinical factors associated with disease severity, the prevalence of non-mild AP was significantly higher in males (21.7%), patients with obesity (BMI ≥ 30 kg/m 2 , 22.5%), and those presenting with CRP levels > 150 mg/L (28.9%). Details of the associated risk factors are presented in Table 3 . Factors associated with development of non-mild acute pancreatitis. AP = acute pancreatitis, BMI = body mass index, CRP = C-reactive protein. According to the Revised Atlanta Classification, 82.2% of patients were classified as having mild AP, while 17.8% had non-mild (moderately severe or severe) disease. In the non-mild group, leukocyte count, hematocrit levels at admission, and peak CRP values were significantly higher. In contrast, serum calcium levels were significantly lower. There were no significant differences in amylase, lipase, or ALT levels between the severity groups. A detailed comparison of laboratory findings is provided in Table 4 . Comparison of laboratory parameters by acute pancreatitis severity. ALT = alanine aminotransferase, CRP = C-reactive protein. Additional analyses were performed to evaluate the relationship between CRP levels and blood group status. The median CRP levels were 128 mg/L (IQR, 62–241) in blood group A, 135 mg/L (IQR, 58–252) in blood group B, 119 mg/L (IQR, 55–230) in blood group AB, and 142 mg/L (IQR, 64–260) in blood group O. CRP levels did not differ significantly across ABO blood groups (Kruskal–Wallis test, P  = .42). When patients were grouped as O and non-O, the median CRP level was 138 mg/L (IQR, 62–255) in the O group and 126 mg/L (IQR, 58–240) in the non-O group. CRP levels were comparable between O and non-O groups (Mann–Whitney U test, P  = .31). Spearman correlation analysis demonstrated no significant correlation between O-group status and CRP levels (rho = .05, P  = .27). The corresponding visual presentations are provided in Figures 1 to 3 . CRP levels according to ABO blood groups. Boxes represent the interquartile range, and the central line represents the median. The median CRP levels were 128 mg/L in group A 135 mg/L in group B 119 mg/L in group AB, and 142 mg/L in group O. No significant difference was observed across ABO blood groups (Kruskal–Wallis test, P  = .42). ABO = ABO blood group system, CRP = C-reactive protein, IQR = interquartile range. CRP levels in O versus non-O groups. Boxes represent the interquartile range, and the central line represents the median. The median CRP levels were 138 mg/L in the O group and 126 mg/L in the non-O group. No significant difference was observed between the groups (Mann–Whitney U test, P  = .31). CRP = C-reactive protein, IQR = interquartile range. Correlation between O-group status and CRP levels. Spearman correlation analysis showed no significant correlation between O-group status and CRP levels (rho = .05, P  = .27). CRP = C-reactive protein. In the non-mild AP group, the need for intensive care, noninvasive ventilation, local complications (pseudocyst and necrosis), length of hospital stay, and mortality rate were all significantly higher. All clinical outcome measures are summarized in Table 5 . Clinical outcomes according to acute pancreatitis severity. AP = acute pancreatitis. When the relationship between ABO blood groups and pancreatitis etiology was analyzed, no statistically significant differences were found among the groups for biliary, idiopathic, alcohol-related, or hypertriglyceridemia-induced pancreatitis ( P  > .05). The etiological distribution by blood group is shown in Table 6 . Distribution of acute pancreatitis etiology by ABO blood groups. ABO = ABO blood group system. These findings reflect the core aim of this study: to assess the potential influence of ABO and Rh blood groups on disease severity in patients with AP and to address a gap in the existing literature. Comparative analysis of our findings with prior research is discussed in detail in the following section.

In this study, we evaluated the association between ABO and Rh blood groups and disease severity in patients with AP. Our results revealed that individuals with blood group O had a significantly higher rate of moderately severe and severe AP. While this finding highlights the potential influence of blood group antigens on inflammatory processes, it diverges from several prior reports. Earlier studies have proposed that individuals with blood group O exhibit lower levels of von Willebrand factor (vWF) and factor VIII, reducing the risk of microvascular thrombosis and potentially contributing to milder clinical presentations in inflammatory or neoplastic conditions. [ 13 ] For instance, Shieh et al [ 12 ] reported that blood group O was more frequently associated with mild AP, whereas higher severity was reported in patients with blood groups A and AB. Similarly, in a Turkish cohort study, Guler and Ustaalioglu [ 9 ] reported that group O was associated with lower mortality and was hypothesized to confer greater resistance to inflammatory responses. In the NAPS2 cohort study by Greer et al, [ 14 ] non-O blood groups were found to be associated with higher risks for both acute and chronic pancreatitis. Conversely, other investigations suggest that blood group O does not consistently provide a protective effect. Amjadi et al [ 15 ] noted that the clinical impact of blood group O may vary depending on the underlying disease context and triggers. Wang et al [ 16 ] suggested that in cases of pancreatitis triggered by viral infections, group O may be linked with increased disease severity. Likewise, Greer et al [ 13 ] associated group O with more aggressive pancreatic cancer phenotypes. Ewald and Sumner [ 17 ] argued that low vWF and factor VIII levels seen in group O may not always be protective and could even increase the risk of complications in certain cases. Moreover, Liufu et al [ 18 ] found that group O was associated with poorer outcomes in patients with sepsis-related thrombocytopenia. In drug-induced pancreatitis, an increased incidence has been reported in individuals with blood group B, particularly in association with azathioprine therapy. [ 10 ] From a biochemical and molecular perspective, the potential relationship between ABO blood groups and the clinical course of AP may be explained through several interconnected mechanisms involving endothelial function, coagulation pathways, microcirculation, and inflammatory responses. ABO antigens are expressed not only on erythrocytes but also on epithelial and endothelial cells, where they may influence cell adhesion, vascular permeability, and immune-mediated inflammatory processes. [ 5 - 7 , 17 ] In addition, ABO blood groups are closely associated with circulating levels of vWF and factor VIII, both of which play important roles in coagulation and microvascular thrombosis. [ 5 , 8 ] Individuals with blood group O generally have lower levels of these procoagulant proteins than those with non-O blood groups, suggesting that ABO-related differences may affect the balance between inflammation, endothelial activation, and coagulation. [ 5 , 8 , 17 ] Since microcirculatory impairment, endothelial dysfunction, and coagulation activation are involved in the progression of AP, ABO-related biological differences may theoretically contribute to variations in disease severity. However, the higher rate of non-mild disease observed in patients with blood group O in the present study does not fully align with the conventional thrombotic-risk pattern reported for non-O blood groups. This discrepancy suggests that the association between ABO blood group and AP severity may be context-dependent and influenced by pancreatitis etiology, population-specific genetic background, inflammatory phenotype, and other unmeasured confounding factors. The findings of our study can be interpreted within this conflicting literature. Notably, the predominance of biliary etiology in our cohort (72.2%) is striking. Gallstone-related pancreatitis tends to present with more severe clinical features, particularly in cases with prolonged biliary obstruction. This may explain the higher severity observed in group O patients, potentially reflecting an etiological imbalance. Additionally, population-level genetic variation, environmental influences, and differences in sample size and selection could have impacted the results. In our study, male sex, obesity (BMI ≥ 30 kg/m 2 ), and elevated CRP levels at admission (>150 mg/L) were all significantly associated with more severe disease. These factors have been consistently recognized as severity determinants in prior research. CRP, in particular, remains a widely used early biomarker for inflammation in clinical practice. Therefore, incorporating fixed genetic traits such as ABO blood group with dynamic biochemical markers may yield a more comprehensive risk stratification strategy in the early phase of the disease. In the additional analyses performed in response to the reviewer’s suggestion, CRP levels were not significantly different across ABO blood groups or between O and non-O groups. Moreover, O-group status was not significantly correlated with CRP levels. These findings suggest that the higher rate of non-mild AP observed in patients with blood group O cannot be explained by CRP levels alone. Therefore, the observed association may be related to mechanisms beyond systemic inflammatory burden, including endothelial function, coagulation pathways, microcirculatory alterations, etiological distribution, or population-specific factors. The impact of the ABO blood group system on inflammatory responses appears to be context-dependent. Although the ABO blood group alone may not serve as a reliable prognostic marker, its integration with clinical risk factors and inflammatory biomarkers could contribute to more effective early risk stratification – particularly in settings with limited healthcare resources. This observation highlights the importance of considering etiological factors, genetic background, and individual inflammatory responses in evaluating disease prognosis. While this study offers novel insights, several limitations should be considered: First, due to the retrospective nature of the study, no causal relationships between variables could be established. The reliance on hospital records limited our ability to assess other potential confounding factors such as genetic mutations, lifestyle habits, dietary patterns, or history of inflammatory diseases. Second, the study was conducted at a single center, which may limit the generalizability of the findings due to regional characteristics and patient profiles. The high prevalence of biliary etiology (72.2%) in Amasya may not be representative of other populations. Third, only hospitalized patients were included. Excluding mild cases managed on an outpatient basis could lead to skewed severity distribution. Although no significant relationship was found between Rh status and disease severity, the relatively small sample size of Rh-negative patients (n = 62) necessitates cautious interpretation. Moreover, all results are based on univariate analyses only, without adjustment for potential confounders. The absence of multivariate statistical modeling is a key limitation, as factors such as comorbidities, medication use, or genetic background could have influenced the observed associations. To overcome these limitations, future research should include prospective, multicenter studies with larger and more diverse cohorts, etiologically balanced subgroups, and integrated genetic analysis. Additionally, translational studies examining the relationship between ABO blood groups and inflammatory biomarkers (e.g., IL-6, TNF-α) would be instrumental in elucidating the pathophysiological mechanisms underlying these associations. Future prospective studies should also evaluate coagulation-related parameters, thrombotic events, comorbid conditions, and inflammatory biomarkers together with ABO/Rh blood group status to better clarify the possible biological pathways linking blood group antigens with AP severity.

The authors gratefully acknowledge the administration of Amasya University Şerefeddin Sabuncuoğlu Training and Research Hospital for facilitating access to hospital data. No individuals are named in this section.