Berkala Ilmu Kedokteran

Sofii et al, Comparison of the diagnostic test of leukocyte count, percentage of neutrophyl, and CRP
Vol. 39, No. 1, Maret 2007: 37-45

Comparison of the diagnostic test of

leukocyte count, percentage of neutrophyl,
and C-reactive protein (CRP) in adult
patients with simple and complicated
acute appendicitis
Imam Sofii, Agus Barmawi, Ishandono Dachlan
Surgery Department,
Faculty of Medicine, Gadjah Mada University/Dr. Sardjito Hospital, Yogyakarta

ABSTRACT
Background: acute appendicitis is one of the acute abdomen conditions that needs an emergency surgical
procedure to prevent severe complication. If the perforation is present, the complications are general
peritonitis, abscess and postoperative complication such as fistula and operative wound infection. Late
diagnosis can increase the mortality and morbidity. There are about 11.2%-30% cases with intestinal
perforation caused by late diagnosis. The leukocyte count, percentage of neutrophyl and C-reactive protein
(CRP) are valuable informations to diagnose the perforation and nonperforation acute appendicitis in adult
patients.
Method: a prospective cross sectional study was held on diagnostic test from patients database for acute
appendicitis cases in Digestive Surgery Subdivision of Dr Sardjito Hospital from December 2005 until
October 2006. The data was classified as simple and complicated acute appendicitis based on the
histopathology result. Eighty two were found for both groups which fulfilled the inclusion and exclusion
criteria. The diagnostic test i.e. sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive
Value (NPV), Likelihood Ratio (LR+), Likelihood Ratio (LR-), accuracy and receiver operating characteristics
(ROC) with area under the curve (AUC) were analyzed for the leukocyte count, neutrophyl, and C-reactive
protein (CRP) in each group with histopathology result as a gold standard.
Result: the leukocyte count, neutrophyl and C-reactive protein (CRP) had respectively sensitivity of: 70,07%;
74,54%; 89,09%; specificity 70,37%; 70,37%; 81,48%; Positive Predictive Value (PPV): 82,97%;
83,67%; 90,74%; Negative Predictive Value (NPV) 54,28%; 57,57%; 78,57%; Likelihood Ratio (LR+)
2,36%; 2,51%; 4,56%, Likelihood Ratio (LR-) 0,42%; 0,22%; 0,13%, area under the curve (AUC)
0,797; 0,744; 0,891, and accuracy 70,73%; 73,17%, 86,56%.
Conclusion: C-reactive protein (CRP) was a better diagnostic test to differ simple from complicated acute
appendicitis in adult patient compared to leukocyte count and neutrophyl.
Key word: simple and complicated acute appendicitis, leukocyte count, neutrophyl, C - reactive protein
(CRP).

Imam Sofii, Agus Barmawi, Ishandono Dachlan, Surgery Department,

Faculty of Medicine, Gadjah Mada University/Dr. Sardjito Hospital, Yogyakarta

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Berkala Ilmu Kedokteran, Volume 39, No. 1, Maret 2007: 37-45

ABSTRAK
Imam Sofii, Agus Barmawi, Ishandono Dahlan: Uji diagnostik jumlah leukosit, persentase neutrofil, dan
CRP pada apendisitis komplikata dan simpleks pasien dewasa.
Latar belakang. Apendisitis akut merupakan salah satu keadaan abdomen akut yang memerlukan tindakan
bedah darurat untuk mencegah komplikasi. Jika terdapat perforasi, maka komplikasi yang timbul adalah
peritonitis general, abses, dan komplikasi pasca operasi seperti fistula dan infeksi luka operasi. Diagnosis
terlambat meningkatkan mortalitas dan morbiditas. Sekitar 11,230% kasus apendisitis akut dengan
perforasi disebabkan oleh keterlambatan diagnosis. Persentase leukosit, neutrofil, dan CRP adalah informasi
yang sangat berharga untuk mendiagnosis apendisitis akut perforasi atau nonperforaasi pada pasien dewasa.
Tujuan. Penelitian ini dimaksudkan untuk mengetahui nilai diagnostik dari jumlah leukosit, persentase
neutrofil, dan CRP pada apendisitis akuta simpleks dengan apendisitis komplikata pasien dewasa.
Bahan dan cara. Dilakukan studi secara potong lintang prospektif mengenai uji diagnostik dari database
pasien apendisitis akut di Subdivisi Bedah Digestif Rumah Sakit Dr. Sardjito dari Desember 2005 Oktober
2006. Data dikelompokkan sebagai appendicitis akut simpleks dan komplikata berdasarkan hasil pemeriksaan
histopatologi. Didapatkan 82 pasien dari kedua kelompok yang memenuhi kriteria inklusi dan eksklusi (27
komplikata dan 55 simpleks). Dilakukan peprhitungan sensitivitas, spesifisitas, nilai ramal positif (NRP),
nilai ramal negatif (NRN), likelihood ratio (LR) positif dan negatif, akurasi, dan receiver operating procedure
(ROC) dengan area under curve (AUC) untuk jumlah leukosit, neutrofil, dan CRP pada tiap kelompok
dengan hasil histopatologi sebagai baku emas.
Hasil. Didapatkan jumlah leukosit, persentase neutrofil, dan CRP berturut-turut mempunyai sensitivitas
70,0%, 74,54%, dan 89,09%; spesifisitas 70,37%, 70,37%, dan 81,48%; NRP 82,97%, 83,67%, dan
90,74%; NRN 54,28%, 57,57%, dan 78,57%; LR+ 2,36%, 2,51%, dan 4,56%; LR- 0,42%, 0,22%,
dan 0,13%; AUC 0,797, 0,744, dan 0,891; akurasi 70,73%, 73,17%, dan 86,56%.
Simpulan. CRP merupakan uji diagnostik yang lebih baik untuk membedakan apendisitis akut simpleks
dengan komplikata pada pasien dewasa di banding jumlah leukosit dan persentase neutrofil.

INTRODUCTION
Acute appendicitis is an acute abdomen
condition which an immediate surgery is needed to
prevent a worse complication. If a perforation
occurred, then complication could happen like a
general peritonitis, an abscess, and postoperation
complication such as fistula and surgical wound
infection1.2.
Appendicitis is one of the emergency diseases
in surgery. Acute appendicitis incidence walks in
line with its lymphoid, with its peak on young adults.
Davies (1997) in his studies in 22 American States
found appendicitis was 0.6% (252,682 cases) from
all the treated patients, with an average of 4 day
treatment, and 3 billion dollar total cost. The number
of treatment days will increase abscess appendicitis
case, peritonitis and postoperation infection1.3.
Factors that influence the delay of acute
appendicitis management which resulted in
complication could be originated from the patients
or medical hands. The patients factor is the
knowledge and cost. As the medical hands factor
are wrong diagnosis, postponing diagnosis, lateness
in sending to the hospital, and postponing surgery3.

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The accurate level of acute appendicitis

diagnosis in some studies is around 76% - 92%.
The lateness of diagnosis could increase the number
of mortality and morbidity. There is a 11.2% - 30%
of late diagnosis resulting in intestinal perforation,
surgical wound infection increased to 17.5%, and
abdominal abscess 15.5%. This condition increases
postoperation complication such as adhesion, socialeconomical burden consequence, lost of working
days and productivity. A simple acute appendicitis
mortality rate is less than 1% (0.12%-0.27%) and
becoming 2.4% if perforation occurred. The
mortality would also be increased in the elderly.
The effort to increase the accurate diagnosis for
acute appendicitis means to decrease morbidity,
mortality and to increase the quality of life postappendectomy4.5.6.
Basic laboratory examination could be used in
acute appendicitis diagnosis. The values of leukocyte,
the percentage of neutrophyl polymorphonuclear
cell, and C-reactive protein (CRP) are signs which
can be sensitive in inflammation process. This
examination is quite easy, quick, and cheap for a
District Hospital7.8.

Sofii et al, Comparison of the diagnostic test of leukocyte count, percentage of neutrophyl, and CRP

Generally, leukocyte increases on acute

appendicitis. The value of leukocyte 11000-14000
per mm 3 occurred in simple appendicitis and
leukocyte more than 18000 per mm3 showed the
presence of perforation/complication. The increased leukocyte showed the presence of bacterial
infection rather than viral. The protein involved in
this acute phase response is called acute phase
protein. CRP is one of the phase component of
acute protein which will be increased 4-6 hours (in
other studies 6-12 hours) after the inflammation
process, seen by serum protein electrophoresis
examination9.10.
This studys aim is to know the sensitivity and
specificity of the leukocyte value as diagnosis test,
neutrophyl, and CRP in simple acute appendicitis
and complicated appendicitis in adult patient
suspected of acute appendicitis. The benefit of this
study is to be able to consider the appendix condition
before surgical, thus can give the right and clear
information to the patient and family concerning
the disease, what should be do, and its prognosis. It
is expected decreasing the morbidity and mortality.

MATERIALS AND METHOD

A prospective cross sectional diagnostic test
study was done on patients with acute appendicitis
in Digestive Surgery, Dr. Sardjito General Hospital,

Yogyakarta from October 2005 until August 2006.

Data were grouped according to simple acute
appendicitis classification and complication based
on histopathology results. 82 samples were
obtained in both groups which fulfill the inclusion
and exclusion criteria. Sensitivity, specificity, positive
predictive value (PPV), negative predictive value
(NPV), positive likelihood ratio (LR +), negative
likelihood ratio (LR -), accuracy and the receiver
operating characteristics (ROC) with an area under
the curve, were calculated based on the data:
leukocyte value, neutrophyl, and C-reactive protein
(CRP) of each groups with a histopathology result
as gold standard. To know the relation between
outside variable with sample, a statistical MannWhitney test was done.

RESULT
From the study done between December 2005
until October 2006 on patients who came to
Emergency Unit of Dr. Sardjito General Hospital,
those suspected suffered from acute appendicitis
and had laboratory examination leukocyte value and
CRP were 82 patients. All patients had appendectomy and the appendixes were sent for histopathology examination.
Out of 82 study samples, there were male
(54.87%) slightly greater compared to female

TABEL 1.The Relation between sex and age with acute appendicitis histopathology result

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Berkala Ilmu Kedokteran, Volume 39, No. 1, Maret 2007: 37-45

(45.12%) with a ratio of 1.21: 1. This result showed

that there was no distribution difference in the total
sample according to sex (p > 0.05). The average
age for simple acute appendicitis was 30.45 +
12.083 years and complicated acute appendicitis
was 35.22 + 14.136 years. There was a slight
difference in the average age of patients with simple
and complicated acute appendicitis. This result was

difference statistically (p > 0.05). From 33 patients,

those who had treatment history were patients
taking medicine (antibiotic) < 12 hours before
laboratory examination were 14 patients (42.42%)
and > 12 hours 19 patients (57.57%). This result
did not show a significant difference statistically (p
> 0.05).

TABLE 2. The relation between the history of treatment and duration of illness with acute appendicitis histopathology result.

RR: relative risk; CI: Confidence Interval; SD: Standard Deviation, *antibiotic

statistically had no significant difference (p > 0.05).

If the sample age was grouped into < 45 years and
> 45 years, the result was relatively no difference
between simple and complicated acute appendicitis.
The risk of complicated acute appendicitis at the
age of > 45 years is 1.24 times compared to the
age < 45 years (RR: 1.24; CI: 0.70-2.20).
TABLE 2, showed that the average duration
of illness of simple acute appendicitis patients was
21.24+20,80 hours (1.33+0.67 days) and complicated acute appendicitis 42.15+26.29 hours (2.11+0.80
days). This result showed a significant difference
between both group (p < 0.05). As many as 33
patients (40.25%) had treatment history before: 21
patients (25.60%) with simple acute appendicitis
and 12 patients (14.63%) with complicated acute
appendicitis. This result showed no significant

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TABLE 3 shows the result of leukocyte,

neutrophyl and CRP cut off point compared to
histopathology result of simple and complicated
acute appendicitis. The cut off point of leukocyte
was 15200 per mm3, neutrophyl 86.5% and CRP
92 mg/L. The cut off point showed high sensitivity
and specitivity.
TABLE 4 shows the result that leukocyte value
of 15200 per mm3, has a sensitivity value of 70.07%,
specificity 70.37%m positive predictive value (PPV)
82.97%, negative predictive value (NPV) 54.28%,
the likelihood ratio (LR+) 2.36%, the likelihood ratio
(LR-) 0.42%; and accuracy 70.73%.
TABLE 5 showed that neutrophyl value 86.5%
had the best diagnostic values i.e. sensitivity
74.54%, specificity 70.37%, positive predictive
value (PPV) 83.67%, negative predictive value

Sofii et al, Comparison of the diagnostic test of leukocyte count, percentage of neutrophyl, and CRP

TABLE 3. The Relation of leukocyte, neutrophyl and CRO values with histopathology of simple
and complicated appendicitis.

(NPV) 57.57%, likelihood ratio (LR+) 2.51%,

likelihood ratio (LR) 0.22%, and accuracy 73.17%.
TABLE 6 shows that CRP value 92 mg/L had
sensitivity value of 89.09%, specificity 81.48%,

positive predictive value (PPV) 90.74%, negative

predictive value (NPV) 78.57%, likelihood ratio
(LR+) 4.56%, likelihood ratio (LR) 0.13%, and
accuracy 86.56%, the best compared to the others.

TABLE 4. The Relation of Leukocyte value with simple and complicated acute appendicitis

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Berkala Ilmu Kedokteran, Volume 39, No. 1, Maret 2007: 37-45

TABLE 5. The diagnostic of neutrophyl value with simple and complicated acute appendicitis

TABLE 7 shows the result of area under the

curve (AUC) which was obtained from the graphic.

The AUC of leukocyte, neutrophyl, and CRP were

0.797, 0.744 and 0.891.

TABLE 6. The Relation of CRP value with simple and complicated acute appendicitis

TABLE 7. The Result of Area Under the Curve (AUC) leukocyte, neutrophyl and CRP

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Sofii et al, Comparison of the diagnostic test of leukocyte count, percentage of neutrophyl, and CRP

FIGURE 1. Receive Operating Characteristik (ROC)

leukocyte, neutrophyl and CRP value to the result of
acute appendicitis histopathology.

Figure 1 shows a Receiver Operating Characteristics (ROC) that illustrates the relation between
sensitivity and specificity values of leukocyte,
neutrophyl and CRP.

DISCUSSION
The history and physical examination are still basic
diagnosis of acute appendicitis. Although there are no
symptoms or clinical signs that can predict accurately
this acute appendicitis, but the combination between
symptoms and signs can support a more accurate
diagnosis. The presence of pain and tenderness on
the right bottom part, migration pain accompanied by
inflammation signs, the increase of temperature,
leukocytes and CRP serum should suspect the presence of acute appendicitis. No signs of inflammation
is still a doubtful diagnosis of appendicitis (positively
fake). The diagnosis of acute appendicitis is sometimes
difficult for infant or elderly patients, thus the number
of complication increases more 8.11.
Chung & Lai (2000) studied on the lateness
diagnosis of acute appendicitis caused by patients,
treated in the emergency unit and the surgeon. It was
found that this lateness was caused by patient factor
in 65 complicated appendicitis cases from 140 cases
(46.4%). The rate of the simple acute appendicitis
patients who were admitted in the hospital was 24.9
hours and for complicated acute appendicitis 42.0
hours. The rate of lateness caused by the treatment
in the emergency unit on acute appendicitis 5.8 hours

and complicated appendicitis 17.9 hours. The rate

of lateness caused by treatment by a surgeon on
acute appendicitis was 10.9 hours and complicated
appendicitis 16.3 hours 6.12.
Antibiotic administration can decrease the number
of complication caused by acute appendicitis. Everson
(1977) in his control study found that 16 out of 19
cases (84.2%) experienced complication without
systemic antibiotic administration, compared to 9 from
30 cases (30%) experienced complication by systemic
antibiotic administration (Ellis, 1989)1.
Styrud (2006) in his randomized controlled
trial (RCT) study compared the usage of antibiotic
and appendectomy on acute appendicitis. As many
as 252 subjects with a suspect on acute appendicitis
was male with the age of 18-50 years. There were
124 subjects in which appendectomy was done, 92%
were simple acute appendicitis, 5% perforated
appendicitis, the rest were with normal appendix, and
14% postsurgery complications. As many as 128
subjects were administered intravenous antibiotic for
2 days and oral as long as 10 days. There were 111
samples (86%) recovered without appendectomy, 18
samples (14%) were appendectomy for 24 hours
observation, and 15 samples (16%) appendectomy
was done with 1 year follow up. There were 6 cases
(5.4%) experienced perforated acute appendicitis13.
The number of complicated acute appendicitis
depends on a lot of factors. Complicated acute
appendicitis in children is 19.0% and adult 13.8%. The
condition of complicated acute appendicitis in children
at the ages of < 6 years and adults >60 years, this is
nearly the same as 10% and 9%. Lee (2006) with
simple acute appendicitis 6.6% and the complicated
one 14.6%. Kozar & Roslyn (1999) found the
number of simple acute 70%, complicated 16% and
the rest is normal appendix2.
Inflammation factor has long been used to
increase the accuracy of the diagnosis of acute
appendicitis. A lot of studies can be found on sensitivity,
specificity, inflammation factor such as leukocyte,
neutrophyl and CRP completed by cut off point and
ROC. Laboratory examination is much used ROC
graphic as well because its cheapness of its easy way
with an exact result, and it is widely available in
hospitals mainly in small cities14.
Korner et al (1999), found an accurate result
based on clinical symptoms in emergency unit
between 70%-80%. To increase accuracy of acute

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Berkala Ilmu Kedokteran, Volume 39, No. 1, Maret 2007: 37-45

appendicitis diagnosis, an examination of leukocyte,

neutrophyl and CRP values is beneficial. Korner
got the result that the perforation appendicitis case
was 49 from 434 cases (11%). The cut off point
for perforation acute appendicitis case was 17200
per mm3, with sensitivity and specificity values were
71% and 61%, AUC was 0.66. The cut off point
for neutrophyl perforation acute appendicitis was
89%, with a value of sensitivity and specificity 88%
and 46%, AUC was 0.68. The cut off point for
CRP perforated acute appendicitis was 101 mg/L,
with sensitivity and specificity 79% and 47%, AUC
was 0.604.
Gronroos & Gronroos (1999) compared leukocyte and CRP value in simple, complicated acute
appendicitis case and normal appendix on 300
patients. In the study the cut off point result of
leukocyte and CRP values of complicated acute
appendicitis were 14300 per mm3 and 99 mg/L. In
this study the sensitivity and specificity were not
mentioned15.
Andersson (2004) in a 24 meta-analysis study
found a result that clinical variables, i.e. peritoneal
irritation symptoms (suppressed pain, loss-pressed
pain, local tenderness and muscular defense) and
moving pain were the main discriminate variable in

acute appendicitis with an UAC 0.78 and 0.68.

Leukocyte, neutrophyl and CRP values had a high
accuracy mainly in perforated acute appendicitis
UAC between 0.85-0.87. Andersson also found result
that perforated appendicitis showed leukocyte cut off
point value 15000 per mm3, with LR+ 7.20%, with
LR- 0.66%, and UAC 0.85. The neutrophyl cut off
point value in perforated acute appendicitis was
90% with a positive likelihood ratio (LR-) 0.39%,
and UAC 0.86. The value of CRP cut off point in
perforated acute appendicitis was 101 mg/L, with
LR+ 4.24%, LR- 0.39%, and AUC 0.878.
Yang et al (2006) found a result that perforated
appendicitis case was 196 from 740 cases (36%).
The cut off point leukocyte value of perforated
acute appendicitis was 14900 permm3. The cut off
point neutrophyl value of perforated acute appendicitis
was 86.4%. The cut off point CRP value of perforated
acute appendicitis was 96.8 mg/L9.
The researcher found the result of perforated
appendicitis case was 27 from 82 cases (32,9%).
The cut off point leukocyte value of perforated
acute appendicitis was 15200 permm3. The
leukocyte value of 15200 permm3, the sensitivity
value 70.07% was obtained, specificity 70.37%,
PPV was 82.97%, NPV 54.28%, LR+ 2.36%, the

TABLE 8. A Result Comparison among some Simple and Complicated Acute Appendicitis studies

LR- 0.42%, the AUC was 0.797, accuracy 70.73%.

The cut off point neutrophyl value in perforated
acute appendicitis was 86.5%. On neutrophyl value
86.5% the sensitivity value was 74.54%, specificity
70.37%, the PPV was 83.67%, the NPV was
57.57%, the LR+ was 2.51%, the LR was 0.22%,
and AUC was 0.744, accuracy 73.17%. The CRP
cut off point value in perforated acute appendicitis
was 92 mg/L with a sensitivity value of 89.09%,

44

specificity 81.48%, PPV 90.74%, NPV 78.57%,

LR+ 4.56%, LR- 0.13%, AUC 0.891, accuracy
86.56%. The AUC was nearly close to 1, showing
that diagnosis test had an increasing sensitivity and
specificity value.
CRP will increase dramatically starting 4-6
hours after the onset of the inflammation and the peak
level occurred on the third day. CRP desensitized by
hepatocyte and a minimum number is desensitized

Sofii et al, Comparison of the diagnostic test of leukocyte count, percentage of neutrophyl, and CRP

by other mRNA cells, such as lymphocyte.

Hepatocytes are stimulated by IL-1, IL-6, TNF and
INF to start sensitizing CRP, just as inflammation
appears. In patients with a suspect of acute
appendicitis, CRP could be used as an indicator of
a continuing inflammation16.17.
Laboratory examination to determine the
diagnosis of a disease is often done with some
laboratory examination at a time. Examining some
tests is useful to diagnose more closely, to increase
the sensitivity and specificity. The method used is
by parallel or serial multiple diagnosis tests. By
parallel multiple diagnosis tests the sensitivity can
be greater, but the specificity value smaller. By a
serial multiple diagnosis tests a reversed result is
obtained, that is the specificity value is greater
whereas the sensitivity value was small18, meaning
that the diagnosis is more accurate.
Examination on acute appendicitis in Emergency
Unit often use more than one laboratory examination.
The result of leukocyte value, neutrophyl and CRP
separately or together often become a consideration
in diagnosing acute appendicitis 9.

CONCLUSION
Laboratory examination on leukocyte,
neutrophyl and CRP values is still a good diagnostic
tool that can be used to compare between simple
and complicated acute appendicitis. CRP
examination has a better result compared to
leukocyte and neutrophyl on simple and complicated
acute appendicitis diagnostic test with sensitivity
89.09%, specificity values 81.48%, with positive
predictive value (PPV) 90.74%, negative predictive
value (NPV) 78.57%, positive likelihood ratio (LR+)
4.56, negative likelihood Ratio (LR-) 0.13.
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