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Second International Virtual Conference of Biotechnology Research Center (IVCBRC-2021)
Journal of Biotechnology Research Center
Vol.15 No.2 P-ISSN: 1815-1140
Published Online: (December) 2021 E-ISSN: 2708-1370
5
The Value of Platelet Indices and platelet to lymphocyte ratio as predictors of severity of
Preeclampsia in Iraqi women
Alea Farhan Salman Ban Hadi Hameed Eham Amer Ali
The National center of Hematology / University of AL-Mustansiriyah / Baghdad - Iraq
AL Yarmouk Teaching Hospital / College of medicine / University of AL-Mustansiriyah / Baghdad - Iraq
Department of Chemistry and Biochemistry / College of Medicine / University of AL-Mustansiriyah / Baghdad - Iraq
Corresponding author: aleafarhan2@gmail.com
Received: 10/ Aug. /2021 , Accepted: 13 /Sep. /2021
Abstract
To assess the significance of platelet indices and the ratio of platelet to lymphocyte as an early prediction
of patients with severity of Preeclampsia. Ninety women were enrolled in three groups: group I: (In=30)
women diagnosed as non-severe preeclampsia, group II: (n=30) women diagnosed as severe preeclampsia,
and group: III (n=30) age-matched normal pregnant women as a control group. The platelet parameters
namely: platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), and platelet
to lymphocyte ratio (P/L ratio) were evaluated and compared among the study groups.Our findings
showed a significant difference among the studied groups regarding the followings: body mass index BMI,
systolic blood pressure (SBP) and diastolic blood pressure (DBP) at P-value < 0.05. Mean Platelet Volume
and Platelet Distribution Width showed no significant differences between the study groups (P= 0.693 and
0.118, respectively). In all groups, highly decrease in platelet count (p = 0.01) and platelet to lymphocyte
ratio (p= 0.024) were found. The changes in the platelet indices are more evident in mothers with severe
preeclampsia especially the ratio between platelet and lymphocyte. Thus, Platelet indices could be used as
biomarkers for early prediction of preeclampsia seriousness.
Keywords: Platelet indices, Platelet /Lymphocyte Ratio, Preeclampsia.
Introduction
Preeclampsia is a multisystem disorder specific to
a pregnancy and remains a significant cause of
maternal mortality throughout the world (1). It can
be characterized by the unusual vascular response
to placentation, correlated with increased resistance
of systemic vascular. Also, abnormal vascular
response associated with enhancement aggregation
of platelet, stimulation of the coagulation system,
impairment in the function of endothelial cells with
decreased perfusion of an organ (2). The criteria for
the diagnosis of preeclampsia need de-novo
hypertension (BP ≥140/90mmHg) and
concentration of proteinuria (≧0.3 g/d which occurs
after 20 weeks of gestation (3).
In a normally state, platelets are inactivated in the
bloodstream. But when any damage or activation of
endothelial wall comes in contact with platelets,
they can be activated (4). In women with risk for
preeclampsia (PE), the activation of platelets begins
early in gestation, however, during the 3rd trimester
of uncomplicated pregnancy the platelets count
decreases by an average of 10% due to
hemodilution (5).
Platelet indices are markers for inflammation
and/or ischemia. Additionally, as a marker of
inflammation and thrombosis, the
Platelet/lymphocyte (P/L) ratio is a newly
introduced tool that is found to be raised (6). New
research indicating that peripheral white blood cell
(WBC) counts, such as the platelet-to-lymphocyte
(P/L) ratio, are indicators of a systemic
inflammatory response that may provide diagnostic
aid and prognostic value for diseases in which
inflammation has been accused as an underlying
cause of disease progression (7). In preeclampsia,
platelet consumption as a result to the abnormal
stimulation of coagulation system, lead to the
thrombocytopenia. Thrombocytopenia occurs in up
to 50% of women with preeclampsia (8). In the
Second International Virtual Conference of Biotechnology Research Center (IVCBRC-2021)
Journal of Biotechnology Research Center
Vol.15 No.2 P-ISSN: 1815-1140
Published Online: (December) 2021 E-ISSN: 2708-1370
6
assessment of preeclampsia, these blood indices are
good predictive tool with low cost. Though the
previous studies showed a good relation between
hematological parameters and preeclampsia, but
with the severe cases where complications are more
common and early diagnosis is vital, these
parameters still need further exploration (9).
Thus, rationale behind this study is to assess the
value of these parameters in the diagnosis of
preeclampsia and its severity in our clinical setting.
Patients and method
The current work involved a total of 90 pregnant
women at Al Yarmouk teaching hospital over a
period of six months. The participants who were
enrolled in this case control study had been
assigned from the outpatient clinic and the
Obstetric ward for the cases (60 women with
preeclampsia) and control group who were attended
the antenatal clinic for routine antenatal visit (30
apparently healthy women) who were matched for
maternal age and gestational age with cases of
preeclampsia. Preeclampsia is diagnosed when the
blood pressure equals or more than 140mmHG for
systolic blood pressure and 90mmHg for diastolic
blood pressure on two occasions 6 hours apart with
proteinuria ++/ High power field or more in urine.
The case group was divided into two subgroups: 30
patients with severe PE when there are features of
severe hypertension or end organ damage and 30
patients with non-severe PE when the hypertension
and proteinuria were mild to moderate with no end
organ affection according to American
classification of preeclampsia (10). These patients
were allocated to the study after clinical
assessment; the blood pressure measurement was
done by mercurial sphygmomanometer with the
patients in sitting position at rest. The
investigations included: complete blood count,
renal function test, liver function test, coagulation
screen, and urine analysis. All participants gave an
informed consent to participate in the study and the
protocol of this work had been licensed by the
medical council of the college.
Statistical Analysis: The statistical package for
social science (SPSS 24) was used for data
interpretation which was expressed as means with
standard deviations and standard errors of the
means. One-Way ANOVA had been applied to
analyze the studied variables with significant results
applied to P value less than 0.05. ROC curve
analysis was applied for the P/L ratio interpretation
to define the diagnostic cutoff criterion.
Results
The clinical parameters of the studied groups are
clarified in table 1, the body mass index, systolic
BP and diastolic BP were significantly different as
P values were less than 0.05. While the maternal
age and the gestational age showed a non-
significant difference.
Table 1: Basic clinical parameters among study groups
Variable
(Mean ± SD)
Severe
Preeclampsia
N.30
Non-severe
Preeclampsia
N.30
Control
N. 30
P- Values
ANOVA
Maternal age (years)
29.63±6.4
27.5 ±7.6
26.36±6.5
0.089
Gestational age (weeks)
36.23±1.6
35.45±2.1
37.21±1.4
0.68
Body mass index
(Kg/m2)
41.23±8.5
39.45±11.2
37.68±3.4
0.001*
Systolic BP (mmHg)
168±6.75
145±4.89
100±8.7
< 0.001*
Diastolic BP (mmHg)
106±8.9
92.56±8.45
76±7.17
0.004*
* Refer for significant reading Abbreviations: SD standard deviation, BP: Blood pressure
The platelet indices studied namely MPV, PDW in
addition to P/L ratio are shown in table 2 which showed a
non-significant difference regarding MPV (severe PE
10.34±0.93, non-severe PE 10.80±1.19, control
10.11±1.03) fL and PDW (severe PE 14.63±2.56, non-
severe PE 13.88±1.88, control 13.48±1.99) fL as P values
were 0.693 and 0.118 consequently. While the P/L ratio
showed a significant difference among the groups (severe
PE 79.28±43.84, non- severe PE 106.77±51.24, control
112.39±52.16) as p value was 0.024.
Second International Virtual Conference of Biotechnology Research Center (IVCBRC-2021)
Journal of Biotechnology Research Center
Vol.15 No.2 P-ISSN: 1815-1140
Published Online: (December) 2021 E-ISSN: 2708-1370
7
Table 2: Platelet parameters among the study groups
Parameter
Groups
Number
Mean
Standard
Deviation
Standard Error
of Mean
ANOVA
P values
Platelets
count/mm3
Severe PE
30
180.34
55.07
11.76
0.01*
Non severe PE
30
216.18
70.12
10.98
Control
30
231.21
25.65
5.4
MPV (fL)
Severe PE
30
10.34
0.93
0.16
0.693
Non severe PE
30
10.18
1.19
0.21
Control
30
10.11
1.03
0.18
PDW (fL)
Severe PE
30
14.63
2.56
0.46
0.118
Non severe PE
30
13.88
1.88
0.34
Control
30
13.48
1.99
0.36
P/L Ratio
Severe PE
30
79.28
43.84
8.00
0.024*
Non severe PE
30
106.77
51.24
9.35
Control
30
112.39
52.16
9.52
* Refer for significant reading
Abbreviations: MPV mean platelet volume, PDW platelet distribution width, P/L platelet / lymphocyte ratio
ROC Curve was applied for P/L ratio for
preeclampsia versus control as shown in figure 1
and it revealed that a criterion for P/L ratio of ≤
82.5 the sensitivity is 43.3% and specificity is
76.7% with area under the curve 0.55 and 95%
Confidence interval 0.41 to 0.68 with a significance
level 0.54.
ROC Curve was applied for P/L ratio for severe
preeclampsia versus non severe cases as shown in
figure 2 and it revealed that a criterion for P/L ratio
of >33 the sensitivity is 100% and specificity is
13.3% with area under the curve 0.54 and 95%
Confidence interval 0.43 to 0.65 with a significance
level 0.50.
Second International Virtual Conference of Biotechnology Research Center (IVCBRC-2021)
Journal of Biotechnology Research Center
Vol.15 No.2 P-ISSN: 1815-1140
Published Online: (December) 2021 E-ISSN: 2708-1370
8
Discussion
Preeclampsia is a significant cause of maternal
and fetal morbidity and mortality because it is
associated with an increased risk of preterm birth,
Intrauterine growth restriction, placental abruption
(8,9). Pregnancy is associated with complex and not
fully understood changes that involve blood
clotting. Information regarding platelet behavior in
normal pregnancy has shown mixed results. PLT
indices are a set of indicators that are used to
measure the number of PLT and PLT morphology
(11). Hence in the present study, an attempt was
made to understand the relationship between the
platelet count, MPV, PDW, and P/L ratio with
preeclampsia and tried to evaluate whether these
parameters could be used as markers in the early
diagnosis of preeclampsia
Preeclampsia can be non-severe and severe.
Severe preeclampsia is characterized by more
substantial blood pressure elevations (systolic
≥160mm Hg, diastolic ≥110mm Hg), a greater
degree of proteinuria (>5g/24 hours), and the
presence of symptoms associated with target organ
involvement (12).
High BMI, especially obesity, increase the risk of
preeclampsia as extensively documented in
multiple studies (13). In this study, we show that by
using BMI as a continuum, we find in both cases
(severe and non-severe) that increased BMI in
pregnant women compered to healthy pregnant
women. Obesity has been shown to represent a
definite risk for the development of preeclampsia
during pregnancy (14). Obese patients present a
metabolic syndrome (MS) characterized by insulin
resistance with an excessive flux of fatty acids and
a proinflammatory state that contribute to
disrupting the equilibrium between immunology,
metabolic alterations, and systemic inflammation
that are necessary for a healthy pregnancy (15) .
In our study, the mean age of study subjects was
27.5 ±7.6 and 29.63±6.4 years old in the non-severe
preeclampsia and severe preeclampsia group. These
findings were comparable to previous reports
published by various researchers in the literature.
Prakash et al. reported mean age of 28.7 ± 3.4
years; however, a study done by Onishi et al.
observed a similar mean age compared to the
present study (16,17). In the present study, most
mothers, i.e., 55.6% and 57.1 %, were in the
gestational age of 35 and 36 weeks in non-severe
and severe preeclampsia groups respectively
PLT count in this study showed a significant
decrease in patients with PE compared to the
control group (180±55.07UL) for severe, (216±
70.12 UL) for non-severe, and (231.21±25.65UL)
for the control group with (P=0.01). This was
consistent with a study have been done by Gupta et
al. that found a significant decrease in PLT count in
PE patients compared to the control group (18).
Additionally, Sameer et al. observed that the PLT
count was significantly lower in PE. The lower
platelet count in preeclampsia is associated with
abnormal activation of the coagulation system and
is believed to reflect increased platelet
consumption. (19).
In the current study, there was a non-significant
difference in MPV and PDW from normotensive
pregnant women, which is the result of an
agreement with Cyehan et al. (20) found no
significant difference in MPV between pre-
eclampsia and the normal pregnant group and also,
Altibas et al. reported that MPV is not a significant
predictor of the severity of preeclampsia (21).
However, Gogoi et al reported non-statistically
significant difference in PDW between PE patients
and controls (22).
In this study focuses on inflammatory markers
i.e. the P/L ratio which showed a significant
difference between the study groups as it was
significantly decreased in women with PE
compared to the control group. This result is in
agreement with previous studies such as Toptal and
colleagues who found a lower P/L ratio in PE
versus normal pregnancies and those with severe
PE comparing with non-severe PE which is an
agreement with our study (23). In subgroup
analysis, Yucel and Ustun found that P/L ratio was
decreased significantly in the patients with severe
PE than in the healthy pregnant women, these
results matched our results (24). Karpas and
colleagues conducted a study of consecutive
pregnant women with PE (non-severe, severe
disease) and healthy pregnant women. They found
decreased P/L ratio in the non-severe PE group
Second International Virtual Conference of Biotechnology Research Center (IVCBRC-2021)
Journal of Biotechnology Research Center
Vol.15 No.2 P-ISSN: 1815-1140
Published Online: (December) 2021 E-ISSN: 2708-1370
9
compared with the control group, However, P/L
ratio was increased in the severe PE group
compared with the non-severe PE group and
healthy pregnant controls (25). Hemostasis and
coagulation abnormalities (possibly due to
endothelial damage), including enhanced platelet
activity, have been implicated in the pathogenesis
of pre-eclampsia (26).Some research reports have
indicated that increased P/L ratio is a sensitive
marker of inflammation and a prognostic marker in
breast cancer, ovarian cancer, and colorectal cancer
(27,28). P/L ratio has been studied in a large
number of epidemiological studies as indicators of
systemic inflammation, and lymphocytes are known
to play an important role in the overall
inflammatory response, reducing number of
lymphocytes induced by programmed cell death
may increase inflammatory damage. P/L ratio has
been reported to reflect hyperactive inflammatory
pathways (29). MPV, PCT, and PDW indices are
known parameters that reflect platelet activation
and modification in the blood hemostatic system,
including endothelial cell damage (30,31). One
study showed disagreement with our findings, that
of Yavuzcan et al (30).
ROC analysis was performed to determine
diagnostic P/L ratio values for preeclampsia. In this
study, P/L ratio cut-off value at ≤82.5 showed
sensitivity 43.3% with higher specificity 76.7% to
differentiate preeclampsia from control whereas the
cut off value >33 showed excellent sensitivity
100% but low low specificity 13.3% to differentiate
severe from non-severe cases. Another study
showed the P/L ratio can differentiate normotensive
pregnant women from preeclamptic pregnant
women at a cut-off value of 80.70 with a sensitivity
of 81.1 % and specificity of 95.1 %. The cut of
value reported by Gezer et al. was 126.8 or higher,
with the sensitivity and specificity of 71.8%
and72.4% respectively to predict preeclampsia (32).
Kholief and his co-workers reported a cut-off value
less than or equal to 77.5 for P/L ratio with 35.71%
sensitivity, 85.71% specificity (33). In this study,
the AUC for P/L ratio showed a statistically non-
significant differences, this is in agreement with
Yucel and Ustun who reported that the AUC for
P/L ratio was not statistically significant (p= 0.104)
(24).
Conclusion
This study showed that platelet count and P/L
ratio decrease while MPV and PDW increase as
pregnancy progresses, and these changes are more
prominent in severe preeclampsia than in non-
severe preeclampsia. It was also found that there is
an association between the P/L ratio and the
severity of preeclampsia, and thus the P/L ratio can
be used as a parameter in the diagnosis and
prediction of severe preeclampsia.
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Journal of Biotechnology Research Center
Vol.15 No.2 P-ISSN: 1815-1140
Published Online: (December) 2021 E-ISSN: 2708-1370
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Corresponding author: aleafarhan2@gmail.com
(PC) (MPV)
(PDW) ( P / L .
(BMI) (SBP) (DBP) .P <0.05
P= 0.693 and 0.118)
(p = 0.01) (p= 0.024)
.
