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Dr.

Kamal Abdulhussein Lafta


M.B.Ch.B
Prof. Zuhair B. Kamal
M.B.Ch.B, C.A.B.S
Dr.Ali Rodan Shuwelif
M.B.Ch.B D.S. C.A.B.S

Complete blood count parameters in the diagnosis of acute appendicitis


Abstract
Background: Inflammation of the appendix is a significant public health problem
Due to the lack of pathognomonic signs or symptoms and the low predictive value of
accompanying laboratory tests, diagnosing acute appendicitis can be challenging. The diagnostic
value of Interleukin-6 has been the subject of several investigations. Those with acute
appendicitis had higher cytokine levels than patients in a healthy comparison group. A number of
diagnostic indicators, such as red cell distribution width, neutrophil-to-lymphocyte ratio, and
mean platelet volume, have been examined to minimize the negative appendectomy rate.
Aim of study: To assess the value of complete blood count parameters in the diagnosis of
acute appendicitis.
Patients & methods: This prospective case series study was conducted in Al-Kindy
Teaching hospital - surgical unit during a period extended for 1 years from September 2018 to
September 2019, where patients suffered from signs and symptoms of acute appendicitis were
interviewed using a predesigned questionnaire including age, gender, clinical signs and complete
blood count. Provisional diagnosis was confirmed by histopathological study control group were
consisted of 50 healthy adults of similar age who were admitted to outpatient check-up clinic.
Results: 115 patients (66 males and 49 females) samples were collected, and based on
histopathological study they were divided into two groups: inflamed appendix [group A] (91
cases) and normal appendix group [group B] (24 cases). Control group were 50 samples [group
C] (27 males and 23 females). The mean age of patients diagnosed as inflamed appendix was
23.2±7.2 year, while the mean age of patients diagnosed as having normal appendix was
20.3±5.1years. the mean age of control group was 28.6±3.6 years. In brief a significant
difference from control group was found for leucocytes, lymphocytes and neutrophils counts,
mean platelet volume, platelet distribution width, neutrophil-to-lymphocyte ratio and Platelet-
Lymphocyte ratio. while red cell distribution width and Platelet crit were not significantly
different from control group.

Conclusion: The use of Platelet-Lymphocyte ratio, neutrophil-to-lymphocyte ratio and platelet


distribution width highly sensitive and highly specific and mean platelet volume can be used as
an aid in the diagnosis of acute appendicitis and reduce the negative appendectomies.
Keywords: Appendicitis, lymphocyte, neutrophil, platelet, mean platelet volume, platicrit
Introduction
Appendix inflammation is a major public health issue, with a lifetime incidence of 8.6% in males
and 6.7 percent in women, with the highest prevalence in the second and third decades of life.
While the rate of appendectomy has dropped in industrialized nations over the previous several
decades, it is still one of the most common emergency abdominal procedures. (1) Appendicitis can
be caused by fecaliths, fibrosis, foreign bodies (food, parasites, calculi), or neoplasia in children.
In adults, it can be caused by fecaliths, fibrosis, foreign bodies (food, parasites, calculi), or
neoplasia. (1) Due to the lack of pathognomonic signs or symptoms and the low predictive value
of related laboratory tests, diagnosing AA can be challenging. (2) Despite the fact that
leukocytosis is beneficial, up to a third of individuals may have a normal white blood cell count.
A "left shift" with a higher number of polymorph nuclear neutrophils and immature cells is
common, although not always. In general, C-reactive protein levels are high. None of these
observations, however, has enough sensitivity or specificity to be used to make a diagnosis..(3)
The diagnostic usefulness of the Interleukin-6 (IL-6) levels in suspected appendicitis has been
studied in several research. In individuals with acute appendicitis, cytokine levels of IL-1, IL-2,
IL-6, IL-8, and IL-10 were higher than in a healthy control group. (3,4) A range of diagnostic
indicators have been explored to minimize the rate of negative appendectomy, including red cell
distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and mean platelet volume
(MPV). (5) Mean platelet volume has been found to represent inflammatory load and disease
activities in various illnesses including preeclampsia, acute pancreatitis, unstable angina,
myocardial infarction and systemic inflammation, such as ulcerative colitis and Crohn's disease.
(5)
Latest studies have shown that acute appendicitis and inflammatory disorders are linked with
NLR, MPV, RDW and PDW. (6) Since CBC is commonly available for regular, affordable and
rapid tests with acute appendicitis, a comprehensive assessment of the parameters of this study is
essential.

The aim of the study: to evaluate complete blood count parameters in the diagnosis of acute
appendicitis (AA).

Patients & method This prospective case series study with double control was conducted in
Al-Kindy Teaching hospital - surgical unit during a period extended for 1 years from September
2018 to September 2019, where patients suffered from signs and symptoms of acute appendicitis
were interviewed using a predesigned form including age, gender, clinical signs and complete
blood count. Provisional diagnosis was confirmed by histopathological study.

Inclusion criteria: In-patients operated with a clinical diagnosis of AA, there were supporting
findings in history, like right lower abdominal pain, nausea and vomiting.

Exclusion criteria: Previous abdominal surgery, pregnant women, receiving medical therapy,
alcohol consumption or tobacco smoking, chronic diseases and morbid obesity.
Control group were consisted of 50 samples, who were selected from healthy adults of similar
age who applied to outpatient check-up clinic. All cases with histopathology results that shows
normal appendix were considered the second control group.

Laboratory analysis: All tests were carried out on blood samples collected through a venous
system and placed in EDTA tubes. For the AA group, any complete blood count (CBC)
performed within 24 hours previous to surgery was acceptable. CBC samples were quickly
examined for WBC count, neutrophil ratio, platelet count, MPV, PDW, and RDW. The NLR and
PLR were computed by dividing the lymphocyte value by the ratio. An automated hematology
analyzer was used to test hematological parameters (ABX Micros ES 60 hematology analyzer,
Horiba, France).The upper limits of the reference intervals were as follows:

 Leukocyte counts (WBC) 3.70-10.1×103/µL,


 Neutrophil (NEU): 1.63-6.96x10³/μL (39.3-73.7%),
 Lymphocyte (LYM): 1.09-2.99x103/μL (18.0-48.3%)
 Red blood cells distribution width (RDW): 11.5%-14.5%,
 Mean platelet volume (MPV) 6.90-10.6 fL
 Platelet: 155-366×10³/μL,
 Plateletcrit= platelet count x MPV / 10000 (PCT): 0.21-0.35 %
 Platelet distribution width (PDW) 16-17.2 %
Ethical considerations: The proposal of the study was fully discussed and approved by the
scientific and ethical committee of Iraqi Board of Surgery. The agreement of scientific
committee in Al-Kindy teaching hospital was taken before start of the study. A written consent
was taken from each patient after full explanation of aim of the study, and ensures that collected
data will be used for research purposes only and will be anonymous.
Statistical analysis: The collected data were introduced into Microsoft excel worksheet 16, and
loaded into IBM – SPSS V26 to be used in statistical analysis. Descriptive statistics were
presented using tables (No. and frequency, means & standard deviations), while Mann-Whitey U
test was used to find out significance of difference between measured variables because of
abnormal distribution of collected data which is essential assumption for t test. P-value less than
0.05 was considered as cut-off point for discrimination of significance. The relevant factors were
further studied to assess the capacity of the variables to predict acute appendicitis, and cutoff
values of parameters for group discrimination were set using receiver operating characteristic
(ROC) analysis. The sensitivity and specificity for each outcome under investigation are
displayed with area under curve (AUC) at each value, resulting in a ROC curve. The cutoff
values for each variable were used to compute the positive predictive value (PPV), negative
predictive value (NPV), and accuracy.
Results: A total of 115 patients (66 males and 49 females) samples were collected, and based
on histopathological study they were divided into two groups: inflamed appendix [group A] (91
cases) and normal appendix group [group B] (24 cases). Control group [group C] were 50
samples (27 males and 23 females). The mean age of patients in group A was 23.2±7.2 year,
while the mean age of patients in group B was 20.3±5.1 years. the mean age of in group C was
28.6±3.6 years. Mean, standard deviation, median, and 1st to 3rd quartile of groups A, B and C
with significance of differences between these groups were shown in table (1). In brief a
significant difference between group A and C were found for WBC, LYM, NEU, MPV, PDW,
NLR and PLR (p value <0.0001). while RDW and PCT there were statistically indifferent (p
value 0.959, 0.711 respectively). While on comparision of group A and B there were significant
difference in regards to LYM, NEU, MPV, PDW, NLR, PCT and PLR. while WBC and RDW
there were statistically indifferent (p value 0.180, 0.791 respectively).

Table (1) comparison of mean, standard deviation, median, and 1st to 3rd quartile of group A, B
and C with significance of differences:
Mean Std. Deviation Median 1st Q – 3rd Q P value P value
A vs C A vs B
WBC Group A 11.70 4.08 10.7 9.4-13.2 <0.0001 0.180

Group B 12.15 2.47 12.0 10.75-14.5

Group C 7.62 1.40 7.90 6.47-8.62

LYM Group A 2.02 0.96 2.0 1.28-2.60 <0.0001 <0.0001

Group B 2.76 0.55 2.65 2.33-3.17

Group C 3.12 0.63 3.31 2.75-3.55

NEU Group A 9.02 3.29 8.3 7.13-10.3 <0.0001 <0.0001

Group B 5.55 1.58 5.2 4.72-6.0

Group C 4.90 1.22 4.77 3.87-5.99

RDW Group A 12.91 0.88 12.90 12.2-13.8 0.959 0.791

Group B 12.87 1.07 12.7 11.75-14.05

Group C 12.93 0.86 12.9 12.2-13.62

MPV Group A 6.17 0.82 6.3 5.8-6.6 <0.0001 <0.0001

Group B 8.35 1.54 8.35 7.07-9.47

Group C 8.75 1.17 8.7 7.6-9.72

PCT Group A 0.289 0.054 0.283 0 .244-0.342 0.711 <0.0001

Group B 0.362 0.023 0.359 0.339-0.387

Group C 0.286 0.055 0.29 0.234-0.336

PDW Group A 17.96 1.55 17.9 17.5-18.4 <0.0001 <0.0001

Group B 16.41 1.12 16.4 15.6-17.1

Group C 16.63 .38 16.7 16.30-16.92

NLR Group A 5.45 3.01 4.32 3.31-7.09 <0.0001 <0.0001

Group B 2.07 0.77 1.94 1.80-2.18

Group C 1.55 .54 1.40 1.16-1.91

PLR Group A 232.09 151.55 173.57 139.25-248.16 <0.0001 <0.0001

Group B 93.34 29.83 95.54 75.93-103.65

Group C 81.44 38.10 71.68 57.36-94.51


Receiver operating characteristic curve of the patient group (group A and group B) was
shown in figures (1,2) and the sensitivity and specificity and area under the curve (AUC) was
shown in table (2) with cut off points above which the test considered positive regarding WBC,
NEU, RDW, PCT, NLR and PLR and the cut off points below which the test considered positive
regarding LYM and MPV. With regards to these cut off points, the positive predictive value
(PPV), the negative predictive value (NPV) and the accuracy of the tests were calculated

Figure (1) ROC curve of WBC, NEU,


RDW, PCT, NLR and PLR

Figure (2) ROC curve of LYM and


MPV

Table (2) cut off points, AUC, sensitivity and Specificity, PPV, NPV and accuracy of the test

Variables Cutoff AUC Sensitivity Specificity PPV NPV (%) Accuracy


levels (95%CI) (%) (%) (%) (%)

WBC 103/µL 11.75 0.411 42.9 45.8 75 17.46 43.48

LYM 103/µL 2.30 0.771 69.2 83.3 93.75 39.22 69.57

NEU 103/µL 5.65 0.904 94.5 70.8 92.47 77.27 89.57

RDW(%) 12.7 0.518 58.2 54.1 82.8 25.4 57.3

MPV (fL) 6.85 0.888 97.8 83.3 95.7 90.91 94.78

PCT (%) 0.346 0.147 23.07 29.16 55.26 9.09 24.3


PDW(%) 17.15 0.882 91.2 83.3 95.4 71.48 89.57

NLR 2.34 0.958 97.8 95.8 98.89 92 97.39

PLR 122.18 0.960 96.7 91.7 97.78 88 95.65

Discussion: The most common laboratory test for diagnosing acute appendicitis is a WBC
count. WBC is the initial indication of appendix inflammation, according to several research. (7)
WBC count was significantly different between group A and C while on further evaluation it was
statistically indifferent from group B (p= 0.180) and at a cutoff level 11.75x103/µL, the
sensitivity and specificity of leukocyte level were 42.9% and 45.8%, respectively. A contrary
result with significant difference was found by Narci et al found cutoff value of 10.4×103/ μL
with a 91% sensitivity and 74% specificity (5). Dinc et al found cutoff value 10.6×103/μL with a
73.1% sensitivity and 94% specificity (8). This variation of results can be explained by the type of
control were be used by these studies, were normal people considered a control group. A
decreased LYM count was significantly associated with acute appendicitis (p<0.0001) and the
LYM cutoff value we reported was 2.30 x103/µL, the specificity 69.2%, the sensitivity is 83.3%,
comparable results found by Virmani et al. who reported a significant difference also with a
cutoff value of 1.89 x103/µL lymphocyte(9). Neutrophil count was elevated in cases of
appendicitis and was significantly from control (p<0.0001) and the cutoff point was 5.65
x103/µL with a sensitivity and specificity of 94.5% and 70.8% respectively. A comparable result
was found by Bilici et al also a significant difference found with a cutoff point 8x103/µL had a
sensitivity and specificity of 84% and 77% respectively (10). In our study we found that RDW not
significantly different from normal and at a cutoff point of 12.7% the sensitivity and specificity
of 58.2% and 54.1% respectively was found a comparable result was found by Narci et al
(p>0.05) with best cutoff point was 15.6% at which sensitivity was 47% and specificity of 67%
(5)
. Mean platelet volume was decreased in cases of appendicitis and significantly different from
control group and at best cutoff point of <6.85fL sensitivity and specificity were 97.8% and
83.3% respectively in this study with a higher sensitivity and specificity in comparison to the
results found in the studies by Bilici et al(11), and Albayrak et al(11), MPV was significantly
lower in the AA group, and at cutoff points (<7.4 fL , <7.6 fL), with a sensitivity and specificity
of 73%-84% and 54%-84%, respectively. While Uyanik et al (12) failed to detect a significant
difference in their study conducted on appendicitis in children (305 case of inflamed appendix
and 305 case of normal and having chronic disease cases as control). This may be explained by
their inclusion of children with chronic diseases as control group and this may affect the
statistical difference between these groups. Plateletcrit was not significantly different from group
C (p value: 0.711) but it was significantly different from group B a result. While in the study
conducted by Gu Nes et al (n=165) who state that there was a statistically significant difference
between groups according to the PCT levels. In their study, they compare cases of histologically
approved appendicitis and histologically approved normal appendix and this significant
difference attributed to the high level of PCT in the cases of negative appendectomies, which
associated with other pathologies other than appendicitis(13). PDW was statistically significant
different from control group (p<0.0001), in this study with cutoff point 17.15% at which
sensitivity was 91.2% and specificity 83.3%. Dinc et al found a significant difference also with a
cutoff point of 32.15% sensitivity and specificity were 97.1% and 93% respectively (8).
Neutrophils to lymphocytes ratio was significantly different from control group with sensitivity
and specificity 97.8% and 95.8% respectively at a cutoff point of 2.34. A significant difference
found by Kahramanca who stated that a cutoff point of 4.68 is associated with sensitivity and
specificity were 65.3% and 54.7%, respectively (6). Another study by Shahab et al (14) showed also
significant difference was found with NLR of 4.7 was cut-off value for appendicitis with
sensitivity of 88.89% and specificity of 90.91%. PLR was significantly different from control
group and at a cutoff point of 122.18 sensitivity and specificity were 96.7% and 91.7%. Cinar et
al estimated that at >155.20 cutoff point sensitivity and specificity would be 77.5% and 74.5%
respectively. (15) comparable result also found by Mehmet et al (16).
Conclusion: The use of the complete blood count parameters PLR, NLR and PDW highly
sensitive and highly specific and MPV can be used as an aid in the diagnosis of acute
appendicitis and reduce the negative appendectomies.
Recommendations: We recommend to use PLR and NLR for diagnosis of acute appendicitis
in combination with clinical diagnosis, to decrease the rate of negative appendectomies.
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