Correlation of red cell distribution width with the severity of acute pancreatitis

Veer Bahadur Singh; Harish Kumar; Rajesh Kumar; Babu Lal Meena; Subhash Chandra

doi:10.4103/jcrsm.jcrsm_42_19

ORIGINAL ARTICLE

Year : 2020 | Volume : 6 | Issue : 2 | Page : 123-128

Correlation of red cell distribution width with the severity of acute pancreatitis

Veer Bahadur Singh¹, Harish Kumar², Rajesh Kumar¹, Babu Lal Meena¹, Subhash Chandra¹
¹ Department of Medicine, S. P. Medical College, Bikaner, Rajasthan, India
² Department of Emergency Medicine, S. P. Medical College, Bikaner, Rajasthan, India

Date of Submission	11-Sep-2019
Date of Decision	17-Jan-2020
Date of Acceptance	19-May-2020
Date of Web Publication	21-Dec-2020

Correspondence Address:
Harish Kumar
B-3 Shastri Nagar, Bikaner - 334 001, Rajasthan
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jcrsm.jcrsm_42_19

Abstract

Aim: The present study was conducted with aim to determine the correlation of red blood cell distribution width (RDW) with mortality in patients of acute pancreatitis (AP).
Materials and Methods: This was a prospective, observational study conducted among the 100 patients, admitted in the Department of Medicine, PBM Hospital, Bikaner, with a definite diagnosis of AP, confirmed both clinically and radiologically. Patients were enrolled justifying predefined inclusion and exclusion criteria. All routine investigations such as complete blood chemistry including RDW, renal function test, liver function test, and random blood sugar, more specific ones such as serum amylase and lipase, and contrast-enhanced computed tomography of abdomen were performed both at the time of admission and discharge. Receiver operating characteristic and logistic regression analyses were employed for evaluation.
Results: Of 100 patients, 69% were male whereas 31% were female. The predominant etiology of AP in our study was cholelithiasis (64%). Mean RDW on the day of presentation and discharge was 14.10 ± 3.12 and 13.56 ± 1.34, respectively. Among the total 38 patients of mild AP, 47.36% (18) had RDW <12.6, 44.7% (17) had RDW ranging from 12.6 to 13.3, whereas only 7.89% (3) had RDW >13.3. From the 62 patients of severe AP, 91.9% had RDW >13.3 and 8.1% had RDW ranging from 12.6% to 13.3%. The total mortality rate of our study was 4%.
Conclusion: It was seen that most of the patients who had severe AP have high RDW. Of the four patients that expired, three had RDW >13.3. Thus, RDW increases with the severity of pancreatitis, which was statistically significant and correlated with mortality among acute AP patients. Hence, RDW can be considered as a convenient, time, and cost-effective method.

Keywords: Acute, distribution, mortality, pancreatitis, red cell, width

How to cite this article:
Singh VB, Kumar H, Kumar R, Meena BL, Chandra S. Correlation of red cell distribution width with the severity of acute pancreatitis. J Curr Res Sci Med 2020;6:123-8

How to cite this URL:
Singh VB, Kumar H, Kumar R, Meena BL, Chandra S. Correlation of red cell distribution width with the severity of acute pancreatitis. J Curr Res Sci Med [serial online] 2020 [cited 2023 May 30];6:123-8. Available from: https://www.jcrsmed.org/text.asp?2020/6/2/123/304204

Introduction

Acute pancreatitis (AP) is characterized by the destruction and inflammation of pancreatic tissue through the activation of pancreatic acinar cells, as a result of being triggered by various factors, and it can cause significant morbidity and mortality. The annual incidence of AP ranges from 13 to 45 / 100,000 persons.^[1],[2]

There are also regional differences in demographic distributions: Alcohol-related pancreatitis is more common in the West and Japan, compared with other Asian countries, and there is a wide variation in the prevalence of a form of chronic pancreatitis (CP) that is endemic to tropical countries (20–125 / 100,000 persons reported in two parts of South India).^[3],[4] A large increase in the incidence of AP and a smaller increase in the incidence of CP have been reported in population studies.^[1],[2],[5]

The increasing incidence of obesity is likely to contribute AP because obesity promotes gallstone formation. It is the most common cause of AP. Other major contributors are increased availability and use of tests to the measure serum levels of pancreatic enzymes, which not only detect milder cases of AP but can also result in over diagnosis.^[6] In the US, use of tests to measure serum pancreatic enzymes reportedly increased by >60% over a 10-year period.^[7]

AP results in >250,000 hospitalizations per year. The median length of hospital stay is 4 days. AP is increasing and is a significant burden on health care costs and resource utilization. Although equal proportions of men and women develop AP, CP (Chronic pancreatitis) is more common among men. The risk of AP progressively increases with age, whereas CP mainly affects middle-aged individuals. Age and sex distribution differ based on etiology. Alcohol-related pancreatitis is more common in men, though sex differences disappear with similar levels of alcohol consumption.^[8]

Studies are needed to determine whether genetic factors increase risk in men. Pancreatitis in women is more likely related to gallstones, endoscopic retrograde cholangiopancreatography, or autoimmune diseases. Variations in age and sex distribution among geographic regions likely arise from differences in etiology.^[9]

The patients who come to the emergency service with a complaint of acute stomach ache and who are diagnosed with AP through clinical, laboratorial, and radiological screening methods should be assessed quickly. Forming risk defining systems and determining the severity of the disease are of great importance in prognosis and how successful the treatment is. In the literature, it has been stated that indicators such as the Ranson criteria and computed tomography (CT) can be used to determine the severity of AP.^[10],[11]

The diagnosis for AP was based on typical clinical presentation, plasma amylase level exceeding 3 times the upper normal level, and/or confirmed pancreatitis by the abdominal computed tomographic scanning or ultrasonography. Clinically, AP ranges from a mild form, edema, and necrosis of the parenchyma, to severe AP involving a systemic inflammatory response syndrome and multi-organ failure. The systemic inflammatory response probably helps to explain the potentially association between RDW and prognosis of AP. Several studies^{[12],[13],[14],[15],[16],[17]} have shown that vascular endothelial cells, lymphocytes, neutrophils, and macrophages were activated when pancreatic acinar cells were damaged in early phase, releasing a large quantity of inflammatory cytokine such as phospholipase, protease, elastase, tumor necrosis factor, nitric oxide, interleukin-6 (IL-6), and IL-8.

What is important is that oxidative stress and MAP kinase expands inflammatory response induced by inflammation factors, contributing to damage of pulmonary capillaries and alveolar epithelial cell through various channels. As a result, systemic inflammation impacts bone marrow function and iron metabolism, and inflammatory cytokines inhibit erythrocyte maturation, leading to newer, larger reticulocytes into the blood circulation, “which correlates with RDW increase;^[18] in addition, increased oxidative stress is able to increase RDW by reducing red blood cell (RBC) survival and releasing large premature RBC into the circulation. Besides, inflammation alters the ion channels and RDW is a calculable measure of variability in the volume of circulating erythrocyte, and higher values signify greater heterogeneity in cell sizes (i.e., anisocytosis). As a part of complete blood count test, it is used in the assessment of patient's disorder, and it is an easy, inexpensive, and routinely reported parameter. RDW is a significant prognostic marker for determining the risk of mortality in a range of clinical manifestations.^[19]

Aim and objective

To estimate the correlation of red cell distribution width with the mortality and severity of AP and its prognostic implication.

Materials and Methods

This was a prospective, observational study with a definite diagnosis of AP made both by clinical examination at bedside and radiological imaging. This study was conducted among 100 patients admitted in the Department of Medicine, PBM Hospital, Bikaner, Rajasthan, from September 2015 to September 2016. Ethical approval was obtained from institutional research ethic committee, and written informed consent was taken from all subjects. Venous samples were drawn within 48 h of the onset of symptoms and sent for routine blood examinations, including measurement of amylase, lipase, and RDW.

Inclusion criteria

All cases of AP based on typical clinical presentation, plasma amylase and lipase level exceeding 3 times the upper normal level, and/or confirmed by abdominal computed tomographic scanning or ultrasonography were included in this study. AP is typically characterized by abdominal pain located in the epigatsric or supraumbilical regions, often radiating to the mid-thoracic portion of the back. Pain usually reaches maximum intensity within 20 min but may have a more gradual onset. The pain from AP is usually sharp, constant, lasts hours to days, and is severe enough to force the patient to visit the emergency room. In mild AP, the pain may decrease when sitting or leaning forward in comparison to lying flat. Nausea and vomiting with or without low-grade fever are the most commonly associated symptoms. The modified CT severity index (CTSI) is an extension of the original CTSI was developed by Balthazar et al. in 1994 for distinguishing mild, moderate, and severe forms of AP.

Scores are generated by estimating pancreatic inflammation and necrosis to give a score

Pancreatic inflammation

0: Normal pancreas
2: Intrinsic pancreatic abnormalities with or without inflammatory in peripancreatic fat
4: Pancreatic or peripancreatic fluid collection or peripancreatic fat necrosis.

Pancreatic necrosis

0: None
2: 30% or less
4: More than 30%.

Extrapancreatic complication

One or more such as pleural effusion, ascites, vascular complications, parenchymal, complications, and/or gastrointestinal involvement

Total score: Total points are given out of 10 to determine the grade of pancreatitis and aid treatment:

0–3: Mild
4–7: Moderate
8–10: Severe.

Patients with the presence of hematologic disease, hypertension, diabetes, malignant tumor, active infections, respiratory diseases and serious cardiovascular disease, presence of known chronic liver and/or kidney diseases, immune system disease recent transfusion history, recurrent AP, CP, and pregnancy were excluded from the study.

Tools of data collection

It will comprise three parts:

Pro forma-I containing structured questionnaire containing personal details of patients, symptoms, past history, personal history
Pro forma-II containing general and systemic examination
Pro forma-III containing investigations and final outcome.

The values of RDW were correlated with at time of admission and subsequently on day 5 and on discharge.

Data analysis

The data were presented in the form of tables, figures, graphs, and diagrams. Continuous variables were presented as mean and standard deviations, while a categorical variable was presented as number and percentage. Suitable statistical software was utilized, wherever necessary, for analysis of data, and appropriate statistical tests were used to find the significance of the findings. P < 0.05 (at 95% confidence interval) was considered to indicate statistical significance.

Results

In our study, of 100 patients, 69 were males (69%) and 31 females (31%). The most common age group affected from AP was 41–60 years of age that constituted about 47% of the study population. In this age group, the most common etiology is cholelithiasis (44.68%), followed by alcohol (42.55%). In our study, the most common presenting manifestation was abdominal pain affecting as many as 90% of the study population. This was followed by fever (82%) and vomiting (80%), whereas abdominal distension and dyspnea were presenting manifestation in 10% of the study population.

82% of the patients had RDW >13.3, 16% of the patients had RDW ranging from (12.6 to 13.3) while 2% of the patients had RDW <12.6 in our study. In our study, the mean RDW at the time of admission was 14.10 ± 3.12. On analysis, it was noted that RDW subsequently decreased as the days progressed and was 13.56 ± 1.34 at the time of discharge. ANOVA test was applied and decrement in RDW value subsequently with the days was found to be statistically significant (P = 0.004) [Table 1] and [Table 2]. AP involves both local inflammatory lesions and systemic pathological damage. Appropriate evaluation of the severity of AP is important for early and effective medical treatment for AP. Out of the 38 patients who had mild AP, 18 patients (47.36) had RDW <12.6, 17 patients (44.73%) had RDW ranging from 12.6 to 13.3, whereas only 3 patients (7.89%) had RDW >13.3. However, among the 62 patients who had severe AP, 91.9% of the patients had RDW >13.3 whereas 8.1% of the patients had RDW ranging from 12.6% to 13.3% [Table 3] and [Graph 1]. It was seen that none of the patients who had severe AP had RDW <12.6. RDW associated with the severity of AP in our study. RDW increases with the severity of pancreatitis which was statistically significant. It was seen that in our study, 74% of the patients recovered completely without any residual stigmata of disease. 22% of patients develop residual stigmata of disease. Out of the four patients who expired, 3 (75%) had RDW >13.3 whereas one patient had RDW ranging 12.6–13.3. Moreover, of 22 patients who develop residual stigmata, only 3 patients (13.64%) had RDW ranging 12.6–13.3% and 19 patients had RDW ranging >13.3. Thus, RDW is a good predictor of mortality and complications [Table 4] and [Graph 2], [Graph 3].

Table 1: Distribution of study population according to red cell distribution width at the time of presentation

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Table 2: Distribution of study population according to red cell distribution width and its progression till discharge

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Table 3: Distribution of study population according to red cell distribution width and severity of acute pancreatitis

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Table 4: Distribution of study population according to red cell distribution width and outcome

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Receiver operating characteristic (ROC) curve analysis was used to evaluate the values for RDW to predict mortality in AP patients. The area under the curve (AUC) and the optimal cutoff value were calculated. The AUC for the RDW value was 0.894 (P < 0.001, 95% confidence interval = 0.823–0.966). The optimal cutoff value to predict deaths was 14.35 (sensitivity = 88.2%, specificity = 91.8%).

Discussion

RDW is a quantitative measure of variability in the size of circulating erythrocytes with higher values, reflecting greater heterogeneity in cell sizes.^[20] The high level of RDW is a novel prognostic marker that may reflect an inflammatory state.^[21] AP is an inflammatory disease, its mechanism is still not completely understood, and early pathophysiological events escape clinical observation.^[22] Early death (within the first week) due to severe AP is generally caused by massive inflammatory responses, which results in multiple organ failure, and late death (after 1–3 weeks) is caused by multiple organ dysfunction with infections and sepsis.^[22],[23] Recent studies found that RDW for predicting mortality was used in cardiovascular diseases, acute dyspnea, and pulmonary diseases.^{[24],[25],[26]} In our study, the mean RDW at the time of admission was 14.10 ± 3.12. On analysis, it was noted that RDW subsequently decreased as the days progressed and was 13.56 ± 1.34 at the time of discharge. ANOVA test was applied and decrement in RDW value subsequently with the days was found to be statistically significant (P = 0.004).

Wang et al. found that approximately 70%–80% of AP is mild AP, which can be treated. In contrast, severe AP develops rapidly and most patients with severe AP, i.e., of MODS within 1 week after disease onset, while others die of infected pancreatic necrosis 1 week after disease onset.^[27] In our study, of 100 patients, 96 patients recovered and 4 patients died from AP. RDW presentation of recovered patients was >13.3 (n = 79), 12.6–13.3 (n = 15) and <12.6 (n = 2). Of four patients who died, we found that the mortality rate was significantly higher in patients with RDW >13.3% than those with RDW <13.3%. Thus, RDW directly correlated with outcome. Therefore, early diagnosis and appropriate treatment are critical for treating patients with severe AP and improving the survival rate of AP.

It has been reported that changes in RDW are associated with the inflammation status of the disease, which may explain why patients with higher RDW values have a higher mortality rate. It has been proposed that inflammation promotes deaths of RBCs or inhibits the maturation of RBCs, which is associated with an increase in RDW.^{[28],[29],[30]} Some inflammatory mediators influence bone marrow function and iron metabolism and suppress erythropoietin-induced maturation of RBCs.^[30],[31] Therefore, RDW values reflect the inflammation status of AP and thus may be used for predicting the severity of AP.

Our study suggests that the severity of AP is greater and patient mortality increased with higher RDW values. In addition, we further assessed the ability of RDW values to predict death in AP patients using ROC curve analysis. We found that the optimal cutoff value for RDW to predict death was 14.35 with a sensitivity of 88.2% and a specificity of 91.8%.

The sensitivity (88.2%) identified in this study is greatly higher than that (47.6) reported by Senol et al.^[19] and the specificity (91.8%) is slightly lower that that (96.3%) reported by Senol et al.^[19] Our study suggests that RDW can be used a sensitive marker for predicting the mortality of AP patients. The optimal cutoff value was 0.894 (P < 0.001, 95% confidence interval =0.823–0.966. The optimal cutoff value to predict deaths was 14.35 (sensitivity = 88.2%, specificity =91.8%) in our study. The same result was found by Wang et al.^[27][Graph 3]. The AUC and the optimal cutoff value were calculated. The AUC for the RDW value was 0.894 (P < 0.001, 95% confidence interval = 0.823–0.966). The optimal cutoff value to predict deaths was 14.35 (sensitivity = 88.2%, specificity = 91.8%).

RDW, as a part of complete blood count test, is used in the assessment of patient's disorder, and it is an easy, inexpensive, and routinely reported parameter. RDW is a significant prognostic marker for determining the risk of mortality in a range of clinical manifestations.^[19]

Conculision

As a part of complete blood count test, it is used in the assessment of patient's disorder, and it is an easy, inexpensive, and routinely reported parameter. RDW is a significant prognostic marker for determining the risk of severity, complication, and mortality in AP patients. Large-scale clinical trials are needed to determine whether an increase in RDW is a marker for early diagnosis and assessment of severity of AP.

RDW is a convenient, economic, and sensitive monitoring method for helping clinicians predict severity, complications, and death. In AP patients, RDW values in combination with other scoring systems will be useful for properly evaluating the severity, mortality, and duration of hospital stay in patients of AP.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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