Mean Platelet Volume (MPV) may Simply Predict the Severity of Sepsis in Preterm Infants

Abstract

Background:
To evaluate the efficacy of serial mean platelet volume (MPV) measurements in diagnosis and followup of sepsis and to compare its effectiveness with C-reactive protein (CRP) and interleukin-6 (IL-6) in sepsis.

Methods:
Preterm infants, whose gestational age and weight were matched to each other, were grouped as control (n = 100) and sepsis (n = 91). Platelet indices (MPV, PDW, platelet count), CRP, and IL-6 levels were measured for the control group and on the day of diagnosis (1st day), 3rd, and 7th days of the sepsis group.

Results:
There were significant differences between the control and sepsis group in terms of platelet count and MPV/PDW levels (p < 0.05). No significant changes were found in either platelet count or MPV and PDW of infants between early and late onset sepsis, nor between culture proven and non proven sepsis, nor among different infectious agents (gram positive/negative and fungal infections) (p > 0.05). Additionally, non-survivors with sepsis had higher levels of MPV and PDW during sepsis episodes on consecutive days (p < 0.05), in contrast to lower platelet counts in non-survivors (p < 0.05). Moreover, a positive correlation was found between MPV and IL-6 and CRP. A MPV value of 10.35 fL was identified as the cut off value in patients probably resulting in sepsis with a sensitivity of 97.8% and specificity of 78.7% (AUC = 0.949; p < 0.001), and a MPV value of 10.75 fL was determined as the cut off value in patients possibly resulting in death at diagnosis with a sensitivity of 95.2% and a specificity of 84.9% (AUC = 0.944; p < 0.001).

Conclusions:
The mean platelet volume can be used in addition to CRP and IL-6 at both diagnosis and follow-up of sepsis and the response of antimicrobial treatment.

Full text

Clin. Lab. 7/2014
1
Clin. Lab. 2014;60:XXX-XXX
©Copyright ORIGINAL ARTICLE
Mean Platelet Volume (MPV) may Simply Predict the Severity of
Sepsis in Preterm Infants
FERHAT CATAL 1, *, CUNEYT TAYMAN 2, *, ALPARSLAN TONBUL 2, HALISE AKÇA 1,
SEMRA KARA 2, M. MANSUR TATLI 1, 2, OSMAN OZTEKIN 3, MEKI BILICI 1
* Ferhat CATAL and Cuneyt TAYMAN are equally the first author
1 Department of Pediatrics, Fatih University Faculty of Medicine, 06510, Ankara, Turkey
2 Department of Neonatology, Fatih University Faculty of Medicine, 06510, Ankara, Turkey
3 Department of Neonatology, Ministry of Health Denizli Public Hospital, Denizli, Turkey
SUMMARY
Background: To evaluate the efficacy of serial mean platelet volume (MPV) measurements in diagnosis and follow-
up of sepsis and to compare its effectiveness with C-reactive protein (CRP) and interleukin-6 (IL-6) in sepsis.
Methods: Preterm infants, whose gestational age and weight were matched to each other, were grouped as control
(n = 100) and sepsis (n = 91). Platelet indices (MPV, PDW, platelet count), CRP, and IL-6 levels were measured
for the control group and on the day of diagnosis (1st day), 3rd, and 7th days of the sepsis group.
Results: There were significant differences between the control and sepsis group in terms of platelet count and
MPV/PDW levels (p < 0.05). No significant changes were found in either platelet count or MPV and PDW of in-
fants between early and late on-set sepsis, nor between culture proven and non proven sepsis, nor among different
infectious agents (gram positive/negative and fungal infections) (p > 0.05). Additionally, non-survivors with sepsis
had higher levels of MPV and PDW during sepsis episodes on consecutive days (p < 0.05), in contrast to lower
platelet counts in non-survivors (p < 0.05). Moreover, a positive correlation was found between MPV and IL-6 and
CRP. A MPV value of 10.35 fL was identified as the cut off value in patients probably resulting in sepsis with a
sensitivity of 97.8% and specificity of 78.7% (AUC = 0.949; p < 0.001), and a MPV value of 10.75 fL was deter-
mined as the cut off value in patients possibly resulting in death at diagnosis with a sensitivity of 95.2% and a
specificity of 84.9% (AUC = 0.944; p < 0.001).
Conclusions: The mean platelet volume can be used in addition to CRP and IL-6 at both diagnosis and follow-up
of sepsis and the response of antimicrobial treatment.
(Clin. Lab. 2014;60:xx-xx. DOI: 10.7754/Clin.Lab.2013.130501)
KEY WORDS
sepsis, platelet indices, MPV, newborn, diagnosis,
follow-up
INTRODUCTION
Neonatal sepsis (NS) is the term used to describe any
systemic bacterial infection in the first month of life.
NS still remains a major contributing factor to the mor-
bidity and mortality of newborn infants, despite the de-
velopment of newer, potentially better microbial agents
[1]. Early signs and symptoms of sepsis may be nonspe-
cific and subtle and might be easily confused with other
non-infectious causes [2]. Although NS can present at
any point in the clinical course, it can be classified into
two relatively distinct illnesses based on the postnatal
age at on-set. Early on-set sepsis occurs during the first
3 - 4 days of life is believed to be the result of maternal
factors such as chorioamnionitis [3]. Late on-set sepsis
typically occurs after 3 days of life and results from en-
dogenous hospital flora. Its incidence ranges from 1 to
10 cases per 1000 live births with a high mortality rate
even with antibiotic therapy [4]. A definitive diagnosis
of neonatal sepsis can be made only with a positive
blood culture. However, it may yield false positive re-
sults due to contamination or negative results even with
_____________________________________________
Manuscript accepted September 5, 2013

F. CATAL et al.
Clin. Lab. 7/2014
2
severe infection. The most important approach is the
availability of early diagnosis and early treatment of in-
fants with sepsis. Therefore, antibiotic therapy should
be promptly initiated until the clinical and laboratory
improvement is achieved [1-5].
Sepsis is a non-spesific inflammatory defense mecha-
nism and is considered a generalized process where ev-
ery organ and system can be involved. The haemostatic
system is frequently disturbed during sepsis. In particu-
lar, in newborn infants, a close relationship between sep-
sis and thrombocytopenia and other changes in platelet
indices such as increased mean platelet volume (MPV)
has been suggested by a few studies [6-8]. The aim of
the present study was to evaluate platelet kinetics and
indices in preterm infants with sepsis and to attempt to
demonstrate if there are any differences with regard to
early and late on-set on-set of sepsis, causative agents,
and mortality.
MATERIALS AND METHODS
The study was conducted from January 1, 2005 to Janu-
ary 1, 2010 in the neonatal intensive care unit, Fatih
University Faculty of Medicine, Ankara, Turkey. Ethi-
cal approval was obtained from the hospital’s ethics
committee and informed consent was obtained from all
parents. Infants with sepsis were enrolled to the study,
and infants without sepsis were selected as controls.
Gestational age was determined by clinical data and by
a first trimester ultrasound scan. Maternal age, maternal
medical diseases, maternal infection (e.g., chorioamnio-
nitis, urinary tract infection), and antenatal and postna-
tal follow-up medical problems were obtained from ob-
stetrics and gynecology department records. Modes of
delivery (vaginal (NVY) or cesarean section (C/S)),
gender, birth weight, and APGAR scores at 1st and 5th
minutes were recorded.
During the study period, infants were divided into two
groups, sepsis and control (no sepsis). The first episode
of sepsis in any enrolled infant was taken into account
to avoid the confounding effects of previous infections
due to prolonged thrombocytopenia during the time of
infection. Sepsis were defined according to criteria de-
termined by Gitto et al. [9]. Based on these criteria, in-
fants with high probable sepsis and probable sepsis
were allocated as the sepsis group. However, infants
who had received antibiotics at admission and infants
with possible sepsis were excluded from the study. In-
fants with neonatal hypoglycemia, hyperbilirubinemia,
and who had no signs of clinical and laboratory infec-
tion were selected as the control group. Temperature in-
stability, apnea, need for ventilation and supplemented
oxygen, tachycardia/bradicardia, hypotension, feeding
intolerance, abdominal distension, and necrotizing en-
terocolitis were recognized as the clinical signs of sep-
sis. The changes in hematologic parameters were de-
fined accordingly; leukocytosis was identified as leuko-
cyte count ≥ 20000/µL, leukopenia was identified as
leukocyte count ≤ 5000/µL and absolue neutrophil
count < 1800/µL. Thrombocytopenia was defined as
platelet count < 100000/µL. A blood smear was evalu-
ated for all infants for the findings of infection, and
band/total neutrophil ratio > 0.2 was considered signifi-
cant.
Sample collection and measurements
Blood was drawn from the infants, who had the clinical
signs of sepsis, from either the peripheral vein, arteria
or a central catheter for evaluation of whole blood
count, C-reactive protein (CRP), and interleukin- 6 (IL-
6) serum levels at diagnosis. This procedure was repeat-
ed three times: at diagnosis, 3 and 7 days of sepsis.
One milliliter of blood was collected into a Kз EDTA
tube (tripotassium ethylenediaminetetraacetic acid) and
counts were performed within 1 hour of sample collec-
tion. Hematological parameters were determined with a
Sysmex-XT-2000i counter (Sysmex, Kobe, Japan). Two
milliliters of blood were drawn into serum tubes (Mini-
collect ® 1cc, Grenier Bio-one, Kremsmünster, Austria)
for evaluation of CRP and IL-6 serum levels. Serum
CRP levels were measured with a nephelometric meth-
od (sensitivity value = 0.8 mg/dL) (CRP kit, Roche,
Germany) (IMMAGE device, Beckman-Coulter, USA).
IL-6 levels were measured with solide phase enzyme la-
belled chemiluminescent immunometric assay (IL-6 kit,
Siemens Healthcare Products Ltd, Hanbers, USA) (sen-
sitivity value = 2 pg/mL) (Immulite 2000 device, USA),
and values were recorded. Additionally, before starting
the antimicrobial therapy, blood samples for culture
were obtained from neonates with sepsis. Cerebrospinal
fluid (CSF), urine, trachela and gastric material were al-
so sent out for culture, if obtained. Blood and CSF cul-
tures were analyzed using fully automated BACTEC
method by BACTEC 9240 device (Becton Dickinson,
Heidelberg, Germany). Infants who had positive blood
culture were treated according to the culture antibio-
gram results. The therapy was ceased, after clinical and
laboratory improvement was achieved.
Statistical analysis
Statistical analysis was performed by SPSS 15.0 statisti-
cal package program (Chicago, IL, USA). The normal
distribution of variables was tested with Shapiro-Wilk
test. Student’s t-test was used to compare for parametric
variables; however, yhe Mann-Whitney U test was used
for intergroup comparisons of nonparametric variables.
Chi-square test and Fischer’s exact test were used to
compare categorical variables for independent groups.
Correlation was performed by Spearman’s correlation
analysis. Logistic regression analysis was used to pre-
dict sepsis and mortality risk. Receiver-operating char-
acteristics (ROC) analysis was performed for cut-off
values of MPV for sepsis and death. Values of p < 0.05
were considered significant. Descriptive statistics were
given as mean and standard deviation (SD) or median
and interquartile range (IQR); categorical variables
were given as values and percent.

MEAN PLATELET VOLUME FOR SEPSIS IN PRETERM INFANTS
Clin. Lab. 7/2014
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Table 1. Characteristics of the study groups.
Variables
Control (n = 100)%
Mean ± SD
Median (IQR)
Sepsis (n = 91) 8.5%
Mean ± SD
Median (IQR)
P
Gender
Boy
46/46%
44/45.4%
0.13
Girl
54/54%
47/51.6%
Birth weight (g)
1350 (250)
1370 (240)
0.83
Gestational age (week)
29.5 ± 0.5
29.4 ± 0.4
0.58
Modes of delivery
NVD
44 (44%)
39 (42.8%)
0.32
C/S
56 (56%)
52 (57.2%)
0.28
APGAR 1. min.
6 (2)
5 (2)
0.29
APGAR 5. min.
7 (2)
6 (3)
0.39
Mother’s age (year)
28.4 ± 0.6
27.9 ± 1.3
0.38
Maternal infection
25 (25%)
48 (52.7%)
0.002 *
Mechanical ventilation therapy
81 (81%)
72 (79%)
0.27
White blood cell count 1st day (x 103/µL)
12.6 (6.9)
17.4 (10.1)
< 0.001 *
IL-6 (pg/mL)
12.1 (19.4)
51.6 (76.5)
0.015 *
CRP (mg/L)
1 (0.2)
5.7 (16.5)
< 0.001 *
Hemoglobin (gr/dL)
16.6 (3.7)
16.3 (3.1)
0.031 *
MCV (fL)
109 (14)
108 (12)
0.008 *
Hematokrit (%)
50.2 ± 1.7
49.8 ± 0.6
0.24
* - p < 0.05 is significant.
Table 2. Platelet count and platelet indices of sepsis and control groups on the 1st, 3rd and 7th days.
Variables
Control
mean ± SD
Sepsis 1st Day
mean ± SD
Sepsis 3rd day
mean ± SD
Sepsis 7th day
mean ± SD
P
Platelet count (x 103/µL)
270.8±98
260.5 ± 65
231.5 ± 89
240 ± 59
< 0.05 *
MPV (fL)
8.3 ± 0.3
10.2 ± 0.5
10.4 ± 0.7
10.3 ± 0.9
< 0.05 **
PDW (%)
16.6 ± 0.2
16.8 ± 1.1
17.3 ± 0.1
16.3 ± 3.1
> 0.05
* - Significant differences between control and sepsis group in terms of platelet count on the 3rd and the 7th day.
** - Significant differences between control and sepsis group related to MPV on the all days of sepsis.
RESULTS
A total of 1072 preterm infants were evaluated during
the study period, and 91 (8.5%) infants with sepsis were
enrolled to the study. A hundred infants from the entire
population without sepsis were selected as the control
group by a simple randomization method using the table
of random numbers. There were no significant differ-
ences between the study and the control groups in terms
of gestational age, modes of delivery, gender, birth
weight, APGAR scores and mechanical ventilation ther-
apy (p > 0.05) except maternal infection (p = 0.002),
white blood cell count (p < 0.001), IL-6 (p = 0.015), and
CRP (p <0.001) serum levels. Table 1 summarizes the
characteristics of the control and sepsis groups. Platelet
indices, including platelet count, MPV, PDW were
evaluated between control and sepsis groups. There
were significant differences between the control and
sepsis group in terms of platelet count on the 3rd and
the 7th day (p < 0.05), in addition to significant differ-
ences between control and sepsis group related to MPV
on all consecutive days of sepsis (p < 0.05) (Table 2).
Infants were divided into two different groups accord-
ing to time at on-set of sepsis, early on-set (n = 23,
25.3%) and late on-set (n = 68, 74.7%). No significant
differences were found between early on-set and late

F. CATAL et al.
Clin. Lab. 7/2014
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Table3. Platelet count and platelet indices of the sepsis groups according to time of onset of sepsis.
Variables
Early onset Sepsis
(n = 43) 47.3%
mean ± SD
Late onset Sepsis
(n = 48) 52.7%
mean ± SD
P
1st day
Platelet count (x103/µL)
245 ± 116.8
286 ± 91.7
> 0.05
MPV (fL)
10.6 ± 0.6
10.8 ± 0.4
PDW (%)
16.5 ± 2.2
16.7 ± 2.5
3rd day
Platelet count (x103/µL)
255.6 ± 78
248.7 ± 89
> 0.05
MPV (fL)
10.2 ± 1.1
10.4 ± 0.9
PDW (%)
17.1 ± 1.5
16.8 ± 1.3
7th day
Platelet count (x103/µL)
283.5 ± 110
274.7 ± 118.4
> 0.05
MPV (fL)
10.7 ± 0.9
10.8 ± 0.8
PDW (%)
16.8 ± 2.7
17.1±2.9
* - No significant differences were found between both groups on consecutive days.
Table 4. Platelet and indices according to Gram-positive, Gram-negative and fungal sepsis.
Variables
Gram-positive
(n = 43) 64%
mean ± SD
Gram-negative
(n = 13) 19.4%
mean ± SD
Fungal sepsis
(n = 11) 16.6%
mean ± SD
P
1st day
Platelet count (x103/µL)
225 ± 106.8
216 ± 111.4
221 ±115.5
> 0.05
MPV (fL)
10.4 ± 0.5
10.3 ± 0.4
10.4 ± 0.3
PDW (%)
16.2 ± 2.3
16.4 ± 1.9
16.4 ± 2.0
3rd day
Platelet count (x103/µL)
198.6 ± 148
201 ± 88.3
191.4 ± 103
> 0.05
MPV (fL)
10.6 ± 1.1
10.4 ± 0.9
10.5 ± 0.8
PDW (%)
16.6 ± 1.3
16.8 ± 1.4
17.1 ± 1.1
7th day
Platelet count (x103/µL)
185 ± 91.1
179.7 ± 114.8
182 ± 97.5
> 0.05
MPV (fL)
10.5 ± 0.7
10.6 ± 0.8
10.5 ±0.9
PDW (%)
16.7 ± 2.6
16.8±2.3
17.0 ± 1.9
* - Significant differences were not found among groups on consecutive days.
Table 5. Platelet count and platelet indices in survivors (n = 70, 77%) and non-survivors (n = 21, 23%) on consecutive days.
Variables
Sepsis 1st Day
mean ± SD
Sepsis 3rd day
mean ± SD
Sepsis 7th day
mean ± SD
P
Platelet count survivors (x103/µL)
260.5 ± 65
231.5 ± 89
240 ± 59
< 0.05 *
Platelet count non-survivors (x103/µL)
179.4 ± 78
152.6 ± 53
114.5 ± 39
MPV survivors (fL)
10.34 ± 0.2
10.1 ± 0.8
10.2 ± 0.9
< 0.05 *
MPV non-survivors (fL)
10.6 ± 1.2
10.8 ± 1.4
11.1 ± 1.1
PDW survivors (%)
16.7 ± 1.2
16.9 ± 0.7
16.6 ± 2.3
< 0.05 *
PDW non-survivors (%)
17.4 ± 1.2
18.6 ± 2.5
19.1 ± 1.5
IL-6 (pg/mL) survivors
647.4 ± 88.9
424.6 ± 65.3
118.6 ± 45.7
< 0.05 *
IL-6 (pg/mL) non-survivors
867 ± 128.6
856.3 ± 144.8
948.3 ± 225.8
CRP (mg/L) survivors
168.3 ± 54.8
112.7 ± 32.8
65.5 ± 16.5
< 0.05 *
CRP (mg/L) non-survivors
222.6 ± 76.4
267.8 ± 110.6
311 ± 128.6
* - Significant differences between survivors and non-survivors.

MEAN PLATELET VOLUME FOR SEPSIS IN PRETERM INFANTS
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5
Figure 1. ROC curve, representing AUC (area under the curve) for sepsis.
Figure 2. ROC curve, indicating AUC (area under the curve) for death.
on-set of sepsis groups in terms of gestational age,
modes of delivery, gender, birth weight, APGAR scores
and mechanical ventilation therapy, maternal infection,
white blood cell count, IL-6, and CRP serum levels (p >
0.05) (data were not indicated). Furthermore, there were
no significant differences between early and late on-set
of sepsis related to platelet count, MPV, and PDW lev-
els on the 1st, 3rd and 7th days of sepsis (p > 0.05) (Ta-
ble 3).
Sixty seven infants had positive blood cultures and 24
infants had negative blood cultures. There were no sig-
nificant differences between culture proven and non-
proven sepsis related to gestational age, modes of deliv-
ery, gender, birth weight, APGAR scores and mechani-
cal ventilation therapy, maternal infection, white blood
cell count, IL-6 and CRP serum levels, and platelet in-

F. CATAL et al.
Clin. Lab. 7/2013
6
dices (platelet count, MPV, and PDW levels) on the 1st,
3rd and 7th days of sepsis (p > 0.05) (data were not in-
dicated). Of all infants with culture proven sepsis, 43 in-
fants (64%) had positive blood culture for gram positive
sepsis (36 staphylococus epidermidis, 5 group B strep-
tococus, 2 enterococcus faecalis), 13 (19.4%) for gram-
negative sepsis (8 Escherichia coli, 4 Klepsiella pneu-
monia, 1 Pseudomonas aeruginosa), and 11 (16.6%) for
fungal sepsis (7 Candida albicans, 4 Candida parapsi-
losis). There were no significant differences among
groups on consecutive days in terms of platelet count,
MPV, and PDW levels on the 1st, 3rd and 7th days of
sepsis (p < 0.05) (Table 4).
Twenty one infants with sepsis (23%) died during the
sepsis episode. No significant differences were found
between survivors and non-survivors related to gesta-
tional age, modes of delivery, gender, birth weight, AP-
GAR scores and mechanical ventilation therapy, mater-
nal infection, white blood cell count (p > 0.05) (data
were not indicated), but IL-6 and CRP serum levels
were significantly different between survivors and non-
survivors (p < 0.05). As shown in Table 4, IL-6 and
CRP serum levels had a gradual decrease on consecu-
tive days in survivors. It may be due to a response to an-
tibiotic treatment. On the other hand, IL-6 and CRP se-
rum levels in non-survivors continued to be higher than
survivors on each consecutive day.
Significant differences were found between survivors
and non-survivors in terms of platelet count, MPV, and
PDW levels on the 1st, 3rd and 7th days of sepsis (p <
0.05) (Table 5). Platelet counts in non-survivors were
significantly lower than the values observed in survi-
vors at all consecutive days (p < 0.05), and a gradual
decrease was seen in non-survivors with a nadir platelet
count range of 37 - 132 x 103/µL on the 7th day of sep-
sis. However, MPV and PDW levels in non-survivors
were significantly higher than those in survivors on
consecutive days, and a daily increment was observed
in non-survivors (Table 4). Additionally, it was found
that platelet count was correlated negatively with MPV
(Rho = - 0.852, p = 0.01) and PDW (Rho = - 0.765, p =
0.014), and a positive correlation was found between
MPV and PDW (Rho = 0.791, p = 0.022). Moreover, a
positive correlation was found between MPV and IL-6
(Rho = 0.640; p = 0.020) and CRP (Rho = 0.538; p =
0.022). Logistic regression analysis of MPV was per-
formed for prediction of sepsis and death. A MPV value
of 10.35 fL was identified as the cut off value in pa-
tients probably resulting in sepsis at diagnosis with a
sensitivity of 97.8% and specificity of 78.7% (AUC =
0.949; p < 0.001) (Figure 1). On the other hand, a MPV
value of 10.75 fL was determined as the cut off value in
patients possibly resulting in death with a sensitivity of
95.2% and specificity of 84.9 % (AUC = 0.944; p <
0.001) at the recruitment time (Figure 2).
DISCUSSION
In the present study, we have evaluated the relevance of
platelet count and platelet indices, particularly MPV, on
preterm infants with sepsis. Our results indicated that
platelet count was observed to decrease, but MPV in-
creased in response to sepsis on consecutive days. These
findings suggested that sepsis affects platelet count and
platelet indices. However, no significant changes were
found in either platelet count or MPV and PDW of in-
fants between those with early and late on-set sepsis.
Additionally, these levels were not different between
culture proven and non-proven sepsis, nor for different
infectious agents (gram positive/negative and fungal in-
fections) as well. Additionally, high MPV and PDW
may indicate the severity of sepsis. Since, non-survivors
with sepsis had higher levels of MPV and PDW than
survivors during sepsis episodes. Thrombocytopenia is a
known fact in preterm infants with sepsis. A close rela-
tionship between sepsis and thrombocytopenia has been
postulated in some studies. Moreover, some studies have
determined a specific platelet response with different de-
grees of thrombocytopenia to different infectious agents,
including gram positive/negative and fungal infections in
preterm infants [10-12]. Therefore, thrombocytopenia
has been reported to be a useful early marker for sepsis.
However, there is still some controversy regarding its re-
liability, whether thrombocytopenia is suggestive of one
(or more) causative agents of neonatal sepsis as other
studies have identified that thrombocytopenia might not
be an organism-specific marker of sepsis [13].
In the present study, our results indicated that sepsis was
associated with lower platelet count in preterm infants.
However, we did not find any specific response, such as
a different level and frequency of thrombocytopenia, to
any different causative microorganism in infants with
sepsis. This may be explained by the fact that the mecha-
nism of thrombocytopenia in septic neonates is believed
to be multifactorial. Since, extensive endothelial injury,
bacterial and fungal toxins, increased platelet activation,
disseminated intravascular coagulation and limited re-
sponse to thrombocytopenia through platelet production
and thrombopoietin in preterm infants, all are thought to
be responsible factors for thrombocytopenia in infants
with sepsis [14,15].
On the other hand, it was suggested that platelet con-
sumption rather than decrased production is the major
contributor to thrombocytopenia, as it was shown that
bone marrow obtained from infants with necrotizing en-
terocolitis that correlated with sepsis proved normal
megakaryocyte number and maturation [16,17]. In neo-
nates, sepsis can be divided into two different types ac-
cording to time of on-set, early and late on-set sepsis.
Early on-set neonatal sepsis (EOS, occurring in the first
72 hours of life) remains an important cause of illness
and death among very low birth weight (VLBW) pre-
term infants [18]. Late on-set sepsis (occurring after 3
days of age) is also an important problem in very low
birth weight (VLBW) infants. Late on-set sepsis is a fre-

MEAN PLATELET VOLUME FOR SEPSIS IN PRETERM INFANTS
Clin. Lab. 7/2014
7
quent and important problem among VLBW preterm in-
fants. Successful strategies to decrease late on-set sepsis
should decrease VLBW mortality rates, shorten hospital
stay, and reduce costs [4]. Therefore, we studied platelet
indices to see their usefulness in early and late on-set of
sepsis. However, in the current study, we could not find
any differences between early and late on-set of sepsis
related to platelet indices (platelet count, MPV, and
PDW levels) on the consecutive days. This means that
platelet indices may not be useful for discrimination and
diagnosis of sepsis according to time of on-set.
IL-6 and CRP are rapid acting acute phase proteins, and
it is known that CRP increases 12 to 24 hours after the
on-set of infection. Furthermore, IL-6 triggers the pro-
duction of CRP from the liver. IL-6 and CRP are the
most commonly used acute phase reactants in neonates
for the diagnosis and follow up of sepsis. Both IL-6 and
CRP are also used to see the effects of the treatment of
infection [19-22]. In the present study, IL-6 and CRP
serum levels had a gradual decrease on consecutive
days in survivors in addition to a gradual decrease on
MPV and PDW levels in survivors. This may be due to
a response to antibiotic treatment. On the other hand,
IL-6 and CRP serum levels with MPV and PDW levels
in non-survivors continued to be higher and a daily in-
crement was observed on each consecutive day. More-
over, a positive correlation was found between MPV
and IL-6 and CRP. Therefore, it may be suggested that
MPV increases parallel to both CRP and IL-6, and those
paramaters decrease parallel to each other during the
sepsis. It might be said that MPV is an accurate, safe
and reliable marker for the diagnosis and follow up of
neonatal sepsis. As it was indicated in our results, MPV
decreases with an adequate response to treatment. MPV
may be used for predicting the severity of sepsis and
death with a high sensitivity and specificity at the diag-
nosis of sepsis and may be a useful marker such as CRP
and IL-6.
In conclusion, this study showed the efficacy of MPV in
the diagnosis and follow-up of sepsis in preterm infants.
Current results also determined that MPV may be used
for predicting the severity of sepsis and death in prema-
ture infants. Moreover the results of the present study
demonstrated that platelet indices may not be useful for
discrimination of sepsis according to time of on-set
(LOS and EOS). Additionally, MPV levels were signifi-
cantly higher at the time of diagnosis and then declined
during the follow-up with treatment that was thought as
a response to treatment. As a result, we suggest that
MPV can be used in addition to CRP and IL-6 at both
diagnosis and follow-up of sepsis and the response of
antimicrobial treatment. Therefore, MPV may be used
in combination with other markers and clinical findings
in sepsis of preterms as well.
Declaration of Interest:
The authors declare that they have no competing inter-
ests.
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Correspondence:
Cuneyt Tayman
MD, Associate Professor
Department of Neonatology
Fatih University Faculty of Medicine
06510, Ankara, Turkey
Tel.: + 90 505 228 36 94
Email: ctayman22@gmail.com