Platelet-to-White Blood Cell Ratio: A Prognostic Predictor for

90-Day Outcomes in Ischemic Stroke Patients with

Intravenous Thrombolysis

Zhibo Chen, MD,* Yuanyuan Huang, MD,* Shanshan Li, MD,† Jie Lin, MD,*
Wenyue Liu, MD,‡ Zhangna Ding, MD,* Xiang Li, MD,* Ying Chen, MD,§
Wanhui Pang, MD,* Dehao Yang, MD,* Zhongqian Su, MD,* Jia Li, MD,*
Yiyun Weng, MD,* and Xu Zhang, MD*

Background: This study is aimed to investigate the relationship between platelet-

to-white blood cell ratio (PWR) and 90-day outcomes in acute stroke patients with
intravenous thrombolysis (IVT). Materials and Methods: A retrospective analysis
was performed on 168 patients receiving IVT for acute ischemic stroke. Complete
blood count evaluation was conducted at admission before IVT. A modified Rankin
Scale (mRS) score of 3-6 at 90 days was considered an unfavorable outcome. Results:
A total of 168 patients were included from 2013 to 2015. The mean age of the sample
was 64.6 (±12.3) years, and 23.2% were women. The median baseline National In-
stitutes of Health Stroke Scale score was 7.5 (interquartile range [IQR] 8.0) and the
90-day mRS score was 2 (IQR 2). In our multivariate logistic regression model, a
PWR greater than 23.52 (odds ratio .454, 95% confidence interval: .212-.973, P < .050)
was a predictor of 90-day outcomes. In addition, there was a significant difference
in the PWR values of patients between favorable outcome and unfavorable outcome
in the large-artery atherosclerosis subtype (28.241 ± 11.581 and 21.899 ± 9.107, re-
spectively; P = .005). Conclusions: The PWR at admission predicts 90-day outcomes
in ischemic stroke patients with IVT. With the easy and routine use of hemogram
analysis, the PWR should be investigated in further prospective randomized con-
trolled trials of acute stroke. Key Words: Outcomes—ischemic stroke—intravenous
thrombolysis—platelet-to-white blood cell ratio.
© 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

From the *Department of Neurology, The First Affiliated Hospi-

tal of Wenzhou Medical University, Wenzhou, China; †Department
of Infection and Liver Diseases, Liver Research Center, The First Af-
filiated Hospital of Wenzhou Medical University, Wenzhou, China;
‡Department of Endocrinology, The First Affiliated Hospital of
Wenzhou Medical University, Wenzhou, China; and §Department of
Ultrasound, The First Affiliated Hospital of Wenzhou Medical Uni-
versity, Wenzhou 325000, China.
Received April 2, 2016; revision received May 16, 2016; accepted
June 8, 2016.
Address correspondence to Yiyun Weng, MD & Xu Zhang, MD,
Department of Neurology, The First Affiliated Hospital of Wenzhou
Medical University, Wenzhou 325000, China. E-mail: drzhangxu@
126.com; wmudrzhangxu@163.com.
1052-3057/$ - see front matter
© 2016 National Stroke Association. Published by Elsevier Inc. All
rights reserved.
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.06.015
Introduction
Stroke is the leading cause of mortality and morbid-
ity worldwide which contributes to the rising costs of
medical treatment and cure.1 Prompt treatment with re-
combinant tissue plasminogen activator (rt-PA) by
intravenous thrombolysis (IVT) has been demonstrated
as the only existing early therapy to restore blood flow
before irreversible damage to brain cells has occurred and
to improve clinical recovery after acute ischemic stroke
(AIS) in some people.2,3 Therapeutic effects indicated by
functional outcomes differ among AIS patients who un-
derwent treatment with IVT with rt-PA.
Thromboembolism, the most common mechanism of
cerebrovascular occlusion, has been considered as a com-
plication of blood vessel injury and systemic inflammatory

2430 Journal of Stroke and Cerebrovascular Diseases, Vol. 25, No. 10 (October), 2016: pp 2430–2438
PWR AS A PREDICTOR OF 90-DAY OUTCOME IN ISCHEMIC STROKE PATIENTS
4
disorders. Platelets play a pivotal role in the process of
thrombosis after they are activated under various con-
ditions, including atherosclerosis, inflammation, and
hemorheology changes.5,6 Activated platelets aggregate at
sites of damaged endothelial cells and participate in the
development of atherosclerotic lesions, which ultimate-
ly leads to intracranial bloodstream interruption by arterial
thrombosis arising from plaque rupture.7-9 Many inves-
tigators have elucidated that higher mean platelet volumes
(MPVs) imply severer stroke and worse prognosis,10-12
whereas lower platelet counts (PLTs) are presented in AIS
patients, and platelets are largely expended with the for-
mation and development of thrombosis.13,14
White blood cells (WBCs) are also implicated in the
pathophysiology of ischemic vascular disease.15 Leuko-
cytes are also recruited with increased tissue damage in
the ischemia area and neutrophils release various inflam-
matory mediators, such as proteases and reactive oxygen
species, which result in endothelium damage and tissue
necrosis.16,17 Elevated peripheral total leukocyte and neu-
trophil counts are also associated with stroke severity on
admission,18 a higher recurrence of ischemic stroke,19 and
even poorer functional outcome.20
Recent studies have also elaborated on the interac-
tions between platelets with leukocytes in ischemic
stroke21 and acute coronary syndrome.22 This interplay
has been elucidated to be correlated with ischemia–
reperfusion injury.23,24 Early prediction for prognosis of
stroke patients with IVT is benefit to attracting the
attention of clinicians at the time of admission, which
may influence the decision of treatment to improve
functional recovery. We for the first time analyzed
peripheral platelet-to-white blood cell ratio (PWR) and
aimed to investigate whether this ratio on admission
was associated with functional outcome for AIS with
intravenous (IV) rt-PA and might be an independent
risk factor for stroke with the other conventional risk
factors. We also investigated the association between
the initial severity of acute stroke and this parameter in
systematically documented patients.
Materials and Methods
Study Population
We conducted a single-center analysis reviewing the
medical records of consecutive AIS patients admitted to
the Department of Neurology, The First Affiliated Hos-
pital of Wenzhou Medical University, recruited from March
2013 to December 2015, and received IVT after in-
formed consent. The diagnosis of AIS was confirmed by
computer tomography perfusion imaging or diffusion-
weighted magnetic resonance imaging; Intravenous rt-
PA (0.9 mg/kg up to a maximum of 90 mg) was used
with 10% of the total dosage as a bolus and the rest over
1 h. No patient received antithrombotic agents within 24
hours after rt-PA infusion.
2431
Exclusion criteria were according to the protocol of the
Safe Implementation of Thrombolysis in Stroke-Monitoring
Study,25 except for the 80-year-old age limit, history of
stroke, and concomitant diabetes. Patients with an onset-
to-treatment time (OTT) of 3-6 hours after symptom onset
were also not excluded. 26 Exclusion criteria also
included patients with hematologic disorders, immuno-
suppressant drug users, those with an infection history
within 2 weeks before onset of stroke, a stroke history
within 6 months, patients with a history of malignancy,
incomplete follow-up, and a baseline modified Rankin
Scale (mRS) score higher than 2. One hundred sixty-
eight patients were included and 22 patients excluded:
five were beyond the therapeutic window, nine had in-
complete follow-up, and eight had insufficient medical
records.
Patients were treated following the guidelines of the
Study Group for Neurologic Diseases of the Chinese
Medical Association. Physical therapy and standardized
rehabilitation were applied when the status of the pa-
tients were stable. The subtypes of stroke were classified
as large-artery atherosclerosis (LAA), cardioembolism (CE),
small-vessel disease (SVD), other determined etiology, and
undetermined etiology.27 Neuroimaging evaluation and
neurofunctional assessments were taken by trained in-
vestigators who were blinded to patient distribution.
Clinical Characteristics and Functional Outcomes
of the Patients
Clinical characteristics of the patients included demo-
graphic findings; medical history such as history of
previous stroke or transient ischemic attack (TIA), atrial
fibrillation, coronary artery disease (CAD), hyperten-
sion, diabetes mellitus, dyslipidemia, and atherosclerosis;
smoking and drinking; medication before admission, which
included therapy with statins, antiplatelets, and antico-
agulants; thrombolysis-related information including OTT,
NIHSS score on admission, and incidence of symptom-
atic intracranial hemorrhage; baseline information including
blood pressure (BP) before treatments, baseline blood
glucose, creatinine, baseline blood PLT, and WBC count;
lipid profile measured within 48 hours after admission,
including total cholesterol, triglyceride, low-density li-
poprotein cholesterol (LDL-C), and high-density lipoprotein
cholesterol (HDL-C); etiology of stroke; mRS score at 3
months; and dosage and type of statin administrated for
at least 3 weeks after the stroke onset. Statin dosages in
the present study were categorized into 2 levels accord-
ing to the attainable reduction of LDL-C described in head-
to-head comparisons, because the efficiency of various
types of statin differs substantially.28 Atorvastatin 20 mg
and rosuvastatin 10 mg were determined as low dose level;
atorvastatin 40 and 60 mg or rosuvastatin 20 mg were
determined as high dose level. All patients had a com-
puted tomography at admission and at 24 hours after
2432
stroke onset, or sooner if neurological worsening was noted.
Symptomatic intracranial hemorrhage was defined as any
hemorrhage with neurological deterioration, meaning an
NIHSS score of 4 or higher than that at admission, or
hemorrhage leading to death.29 Our safety end point was
unfavorable outcome (mRS score ≥ 3) and favorable
outcome (mRS score < 2) at 3 months.
Blood Sample Analysis
A hemogram was evaluated using the peripheral venous
blood samples taken on admission to the emergency de-
partment. The blood sample was collected in a calcium
ethylenediaminetetraacetic acid tube. Complete blood count
evaluation was performed in the hematology laboratory
of our hospital by the hemocounter (XE2100, Sysmex Co.,
Kobe, Japan) to calculate the count of leukocytes and plate-
lets. PWR values were calculated as the count ratio of
platelets to leukocytes in peripheral blood. In addition,
other routine laboratory findings were observed in the
digital record systems in the hospital.
Statistical Analysis
Data were analyzed using SPSS software (version 17.0;
SPSS Inc., Chicago, IL) and presented as mean ± stan-
dard deviation or median (interquartile range [IQR]).
Distribution normality was analyzed with the Kolmogorov–
Smirnov test. The difference between the 2 groups was
tested using independent Student t-tests for normally dis-
tributed variables; the Mann–Whitney U-test was used
for the comparison of nonparametrically distributed vari-
ables. The difference between 3 groups was tested using
analysis of variance for normally distributed variables;
the Kruskal–Wallis test was used for the comparison of
nonparametrically distributed variables. The difference
between categorical variables was determined using the
χ2 test. Mean with standard deviation, median with IQR,
and percentages were used to describe the distribution
of continuous and categorical variables, respectively. The
receiver operating characteristic (ROC) curve was used
to evaluate the prognosis effect of PWR, PLT, and WBC
count on clinical outcome for AIS patients with IVT and
to determine the optimal cutoff value for PWR. Logistic
regression analysis was performed to determine predic-
tors of 90-day functional outcome, and variables with a
probability value less than .10 in univariate logistic re-
gression analysis were determined unbalanced clinical
characteristics. All the unbalanced clinical characteris-
tics and established predictors were then analyzed using
multivariate logistic regression analysis. Statistical sig-
nificance was set at a P value less than .05.
Results
A total of 168 patients were reviewed and included in
this analysis. The mean age of the patient sample was
Z. CHEN ET AL.
64.6 ± 12.3 with 23.2% being female. The median base-
line NIHSS score was 7.5 (IQR 8.0) and the median 90-
day mRS score was 2 (IQR 2). We established a PWR of
23.52 or lower as a preliminary cutoff point for poor
outcome (mRS score 3-6) following AIS with IVT
(χ2 = 10.400; P = .001), and divided the patients into 2
groups: low PWR and high PWR. The characteristics and
laboratory findings in patients with low and high PWRs
are reported in Table 1. The NIHSS scores on admission
to the hospital of patients in the group with low PWR
were significantly higher than those of patients in the group
with high PWR (median 10.0 [IQR 8.5] versus median
6.0 [IQR 7.0], P = .011). There were also significant dif-
ferences in terms of mRS score (median 3.0 [IQR 2.0] versus
median 2.0 [IQR 2.0], P = .003) and OTT (χ2 = 10.162,
P = .006). In addition, there were no statistical differ-
ences between the 2 groups in age, sex, hypertension,
diabetes mellitus, CAD, smoking, drinking, hyperlipid-
emia, atrial fibrillation, previous stroke or TIA, stroke
subtype, systolic BP, diastolic BP, blood glucose, serum
creatinine, total cholesterol, triglyceride, LDL-C, HDL-
C, prior drug use, maintenance of the dose level of statin,
incidence of hemorrhagic transformation, symptomatic ce-
rebral hemorrhage, mortality rate, and so on.
After 3 months, 64 patients (38.1%) had a poor/death
outcome (mRS score ≥ 3). The percentage of patients with
unfavorable outcome was significantly different between
patients with low and high PWRs (50.6% versus 26.4%,
P = .001; Table 1). In the univariate analysis for 90-day
unfavorable prognosis, atrial fibrillation, hyperlipid-
emia, NIHSS score on admission, OTT, stroke subtype,
dose level of statin use, hemorrhagic transformation, symp-
tomatic cerebral hemorrhage, and PWR greater than 23.52
were selected into multivariate logistic regression because
all had P values less than .10 (Table 2). As shown in
Table 2, after adjusting the influences of the factors above
by multivariate logistic regression, PWR greater than 23.52
was an independent predictor for unfavorable outcome
defined as an mRS score of 3 or higher at 3 months
(odds ratio .454, 95% confidence interval [CI]: .212-.973,
P = .042).
ROC curves of PLT, WBC, and PWR to prediction of
90-day outcome are shown in Figures 1-3. The values of
area under the curve were .595 (95% CI: .509-.681, P = .039)
for PLT, .615 (95% CI: .524-.706, P = .013) for WBC, and
.652 (95% CI: .566-.739, P = .001) for PWR. The optimal
cutoff value for PWR, of which the value of the area under
the curve is higher than that of either PLT or WBC, as
a predictor for 90-day unfavorable outcome was determined
as 23.52 in the ROC curve. On this level, the sensitivity
was 64.1% and the specificity was 61.5%. The positive
predictive value of a PWR of 23.52 or lower was 50.6%
and the negative predictive value was 73.6% (Fig 3). There
was a statistically significant difference in 90-day out-
comes between cardioembolic and other groups (χ2 = 6.550,
P = .010; Table 3). However, the PWR values were not
PWR AS A PREDICTOR OF 90-DAY OUTCOME IN ISCHEMIC STROKE PATIENTS 2433
Table 1. Demographic characteristics and laboratory findings in patients with low and high PWRs

Characteristics Total (n = 168) Low PWR† (n = 81) High PWR‡ (n = 87) P value

Age (years), mean ± SD 64.6 ± 12.3 64.3 ± 12.7 64.8 ± 12.0 NS

Female, n (%) 39 (23.2) 19 (23.5) 20 (23.0) NS
Hypertension, n (%) 121 (72.0) 61 (75.3) 60 (69.0) NS
Diabetes mellitus, n (%) 50 (29.8) 25 (30.9) 25 (28.7) NS
CAD, n (%) 14 (8.3) 7 (8.6) 7 (8.0) NS
Smoking, n (%) 69 (41.1) 38 (46.9) 31 (35.6) NS
Drinking, n (%) 55 (32.7) 25 (30.9) 30 (34.5) NS
Hyperlipidemia, n (%) 113 (67.3) 60 (74.1) 53 (60.9) NS
Atrial fibrillation, n (%) 45 (26.8) 23 (28.4) 22 (25.3) NS
Prior stroke or TIA, n (%) 28 (16.7) 16 (19.8) 12 (13.8) NS
Baseline NIHSS score, median (IQR) 7.5 (8.0) 10.0 (8.5) 6.0 (7.0) .011
OTT .006
~180 min 46 (27.4) 13 (16.0) 33 (37.9)
181~270 min 89 (53.0) 49 (60.5) 40 (46.0)
271~360 min 33 (19.6) 19 (23.5) 14 (16.1)
Stroke subtype NS
Large-artery atherosclerosis 107 (63.7) 52 (64.2) 55 (63.2)
Small-vessel disease 13 (7.7) 3 (3.7) 10 (11.5)
Cardioembolic 45 (26.8) 24 (29.6) 21 (24.1)
Other or unknown cause 3 (1.8) 2 (2.5) 1 (1.1)
Systolic BP (mmHg), mean ± SD 153.9 ± 20.3 153.2 ± 20.9 154.5 ± 19.9 NS
Diastolic BP (mmHg), mean ± SD 84.1 ± 12.7 82.6 ± 12.8 85.5 ± 12.5 NS
Glucose (mmol/L), mean ± SD 7.92 ± 2.97 8.36 ± 3.30 7.51 ± 2.579 NS
Creatinine (μmol/L), mean ± SD 73.7 ± 20.9 75.6 ± 19.9 72.4 ± 21.9 NS
Total cholesterol (mmol/L), mean ± SD 5.151 ± 1.093 5.197 ± 1.033 5.108 ± 1.150 NS
Triglyceride (mmol/L), mean ± SD 1.563 ± .986 1.468 ± .838 1.652 ± 1.104 NS
HDL-C (mmol/L), mean ± SD 1.204 ± .334 1.236 ± .352 1.175 ± .316 NS
LDL-C (mmol/L), mean ± SD 3.182 ± .886 3.238 ± .856 3.129 ± .915 NS
Prior drugs, n (%)
Antiplatelet 35 (20.8) 19 (23.5) 16 (18.4) NS
Anticoagulant 6 (3.6) 2 (2.5) 4 (4.6) NS
Statin 6 (3.6) 4 (4.9) 2 (2.3) NS
Statin use, n (%) NS
Not use 3 (1.8) 2 (2.5) 1 (1.1)
Low level* 43 (25.6) 24 (29.6) 19 (21.8)
High level§ 122 (72.6) 55 (67.9) 67 (77.0)
Hemorrhagic transformation, n (%) 38 (22.6) 22 (27.2) 16 (18.4) NS
sICH, n (%) 5 (3.0) 4 (4.9) 1 (1.1) NS
Mortality rate, n (%) 6 (3.6) 5 (6.2) 1 (1.1) NS
mRS score, median (IQR) 2.0 (2.0) 3.0 (2.0) 2.0 (2.0) .003
Unfavorable outcome at 90 days, n (%) 64 (38.1) 41 (50.6) 23 (26.4) .001

Abbreviations: BP, blood pressure; CAD, coronary artery disease; HDL-C, high-density lipoprotein cholesterol; HT, hemorrhagic trans-
formation; IQR, interquartile range; LDL-C, low-density lipoprotein cholesterol; mRS, modified Rankin Scale; NIHSS, National Institutes
of Health Stroke Scale; NS, not significant; OTT, onset-to-treatment time; PWR, platelet-to-white blood cell ratio; SD, standard deviation;
sICH, symptomatic cerebral hemorrhage; TIA, transient ischemic attack.
*Low level: atorvastatin, 20 mg; or rosuvastatin, 10 mg.
†Low PWR: patients with PWR of 23.52 or lower.
‡High PWR: patients with PWR greater than 23.52.
§High level: atorvastatin, 40 and 60 mg; or rosuvastatin, 20 mg.

significantly different among LAA, small-vessel disease, were significantly higher than those of unfavorable outcome
and cardioembolic subtypes (26.107 ± 11.181 versus in LAA stroke (28.241 ± 11.581 versus 21.899 ± 9.107, P = .005;
29.347 ± 7.695 versus 24.505 ± 9.000, respectively; P = .323; Table 3) but were not significantly different in either the
Table 3). In addition, the PWR values of favorable outcome small-vessel disease or cardioembolic subtype.
2434 Z. CHEN ET AL.
Table 2. Logistic regression model with predictors of unfavorable outcome (n = 168)

Variables Unadjusted OR (95% CI) P value Adjusted OR (95% CI) P value

Age 1.022 (.996-1.049) .104 — —

Female 1.348 (.651-2.790) .421 — —
Hypertension .873 (.438-1.739) .698 — —
Diabetes mellitus .778 (.390-1.554) .477 — —
CAD .895 (.286-2.798) .848 — —
Smoking .874 (.463-1.650) .678 — —
Drinking 1.005 (.518-1.952) .987
Hyperlipidemia .565 (.293-1.091) .089
Atrial fibrillation 2.371 (1.182-4.759) .015
Prior stroke 1.269 (.557-2.891) .570 — —
NIHSS score on admission 1.294 (1.186-1.411) <.001 1.265 (1.157-1.383) <.001
OTT
~180 min (reference) — .015 — —
181~270 min .999 (.467-2.134) .998 — —
271~360 min 3.179 (1.253-8.070) .015 — —
Stroke subtype
Large-artery atherosclerosis (reference) — .035 — —
Small-vessel disease .359 (.075-1.705) .197 — —
Cardioembolic 2.254 (1.108-4.584) .025 — —
Other or unknown cause 3.944 (.346-44.972) .269 — —
Systolic BP 1.000 (.985-1.015) .976 — —
Diastolic BP 1.014 (.989-1.039) .284 — —
Glucose .997 (.897-1.107) .949 — —
Creatinine .999 (.984-1.014) .907 — —
Total cholesterol .908 (.681-1.212) .513 — —
Triglyceride .982 (.714-1.351) .911 — —
HDL-C 1.924 (.754-4.911) .171 — —
LDL-C .860 (.600-1.231) .409 — —
Prior drugs —
Antiplatelet .950 (.440-2.051) .896 —
Anticoagulant .806 (.143-4.534) .807 — —
Statin .806 (.143-4.534) .807 — —
Statin use dose level .271 (.138-.533) <.001 .373 (.167-.831) .016
Hemorrhagic transformation 2.499 (1.197-5.220) .015 — —
Symptomatic cerebral hemorrhage 6.867 (.750-62.865) .088 — —
PWR (>23.52)* .351 (.184-.669) .001 .454 (.212-.973) .042

Abbreviations: BP, blood pressure; CAD, coronary artery disease; CI, confidence interval; HDL-C, high-density cholesterol; LDL-C, low-
density cholesterol; min, minute; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; OTT, onset-to-treatment time; PWR,
platelet-to-white blood cell ratio.
*PWR was included in the regression model as a dichotomous variable as above cutoff value (>23.52) and below or equal to the cutoff
value (≤23.52).

Discussion endogenous active phosphoric acid mediator intimately

Atherosclerosis has been the most common pathogen-
esis implicated in the occurrence of cerebral infarction.
At the site of damaged endotheliocytes, the exposure of
vascular collagen increases the contact area with plate-
lets, contributing to the development of thrombosis. In
this process, the aggregation of platelets with fibrino-
gen plays a crucial role.7,8 Among the parameters of
platelets, the increase of MPV reflects the degree of plate-
let activation and the ability to promote the formation
of blood clots.9,10 Platelet activating factor (PAF), an
related with arachidonic acid metabolism, is produced
by a variety of tissues and cells involved in allergy and
inflammatory reaction. With the activation and destruc-
tion of platelets, PAF is released into plasma and results
in further platelet aggregation. The ischemia of paren-
chyma gives rise to excessive production of PAF, which
may be an endogenous toxic nerve agent.30,31 D’Erasmo
et al32 has demonstrated that PLT decreased with in-
creased MPV within 48 hours after onset of stroke and
returned to normal level on the ninth day. PLTs in the
death group have also been illustrated by D’Erasmo et al33
PWR AS A PREDICTOR OF 90-DAY OUTCOME IN ISCHEMIC STROKE PATIENTS
Figure 1. Receiver operating curve of platelet count to prediction of 90-
day outcome in acute ischemic stroke with intravenous thrombolysis. Associated
criterion: less than 203.50; sensitivity: 68.8%; specificity: 51.0%; positive
predictive value: 46.3%; negative predictive value: 72.6%. Area under the
curve: .595 (95% confidence interval .509-.681); P = .039.
to be obviously lower than those in the surviving group,
which may be associated with the prognosis of isch-
emic stroke. However, subsequent research demonstrated
the definite decrease of PLT in ischemic stroke34 without
Figure 2. Receiver operating curve of white blood cell count to predic-
tion of 90-day outcome in acute ischemic stroke with intravenous thrombolysis.
Associated criterion: greater than 9.33; sensitivity: 48.4%; specificity: 77.9%;
positive predictive value: 57.4%; negative predictive value: 71.1%. Area
under the curve: .615 (95% confidence interval .524-.706); P = .013.
2435
Figure 3. Receiver operating curve of platelet-to-white blood cell ratio
to prediction of 90-day outcome in acute ischemic stroke with intrave-
nous thrombolysis. Associated criterion: less than 23.52; sensitivity: 64.1%;
specificity: 61.5%; positive predictive value: 50.6%; negative predictive value:
73.6%. Area under the curve: .652 (95% confidence interval .566-.739);
P = .001.
obvious correlation between PLT and long-term
prognosis.12,34 Recently, Mayda-Domac et al12 concen-
trated on the pathogenicity and predictor of MPV for
cerebral infarction, and PLT has been demonstrated as
an independent risk factor for ischemic stroke, which was
different from previous studies.
Inflammation has been increasingly recognized as a key
contributor to the pathogenesis of atherosclerosis, throm-
bus formation, and ischemic stroke, in which various
elements of the immune system are intimately involved.4
Leukocytes, also called immune cells, play a significant
role in vascular inflammatory injury and secondary pa-
renchyma damage after the onset of stroke. Cytokines and
adhesion molecules regulate the increased migration of
leukocytes to the infarct area.15 Intraparenchymal peri-
vascular neutrophil migration, which occurs within 6-24
hours, is the first response to ischemic brain damage. A
variety of inflammatory mediators and toxic-effective sub-
stances released by immune cells, particularly neutrophils,
may exaggerate brain edema or directly promote the death
of neurons in ischemic and reperfused areas.17 In a clin-
ical investigation, early leukocytosis and neutrophilia have
been reported to be correlated with infarct volume as evalu-
ated by diffusion-weighted magnetic resonance imaging
among patients with AIS,35 and have also been associ-
ated with higher recurrences of stroke.19 Furthermore,
Furlan et al20 suggested that high degrees of peripheral
WBC were a marker of poor neurological prognosis. Also,
low lymphocyte counts with increased counts of monocytes
2436 Z. CHEN ET AL.
Table 3. A comparison of mean platelet-to-white blood cell ratio among stroke subtypes and the relationship between this ratio and
90-day functional outcome for each stroke subtype

Total Favorable outcome Unfavorable outcome

Stroke subtype Mean ± SD n (mean ± SD) n (mean ± SD) P value*

Large-artery atherosclerosis (n = 107) 26.107 ± 11.181 71 (28.241 ± 11.581) 36 (21.899 ± 9.107) .005†
Cardioembolic (n = 45) 24.505 ± 9.000 21 (26.314 ± 7.561) 24 (22.922 ± 9.981) .211
Small-vessel disease (n = 13) 29.347 ± 7.695 11 (29.224 ± 8.421) 2 (30.025 ± .295) .899
P value* .323 .701 .481 —
χ2 6.550 — — .010‡

Abbreviation: SD, standard deviation.

*Comparisons of mean platelet-to-white blood cell ratio of different outcomes of patients for each stroke subtype and different subtypes
of patients with favorable or unfavorable outcome 90-day clinical outcome.
†There was a statistically significant difference in the mean platelet-to-white blood cell ratio between favorable and unfavorable outcomes
for the large-artery atherosclerosis subtype (P = .005).
‡There was a statistically significant difference in 90-day outcomes between cardioembolic and other stroke subtypes (P = .010).

have been proposed by Klehmet et al36 to contribute to
increasing physical susceptibility to poststroke infec-
tion, leading to prolonged length of stay and aggravated
pathogenetic condition.
Increased MPV and platelet distribution width have also
been reported to be associated with thrombolysis failure
in patients with ST-segment elevation myocardial
infarction.37 Previous studies have demonstrated lower
PLTs and larger platelet volumes in patients with acute
coronary syndrome38 and an inverse relationship between
PLTs and MPVs in normal populations.39,40 Larger plate-
lets, with higher physiological activity and greater
glycoprotein IIb-IIIa receptor expression, contain more
prothrombotic mediators and release increased active sub-
stances, which have potent properties to promote
thrombosis5-7 and may influence the recanalization after
IVT. Also, elevated leukocytes are correlated with
thromboresistance, reduced epicardial bloodstream, and
myocardial perfusion, and adverse prognosis of acute myo-
cardial infarction after thrombolytic administration.41 In
experimental models of myocardial ischemia–reperfusion,
leukocytes may contribute to the endothelial dysfunc-
tion and microvascular obstruction, leading to low
myocardial perfusion status,42,43 which is also described
in rat models of ischemic stroke and reperfusion.23,24
Platelet–leukocyte interactions have been increasingly
elucidated to be associated with inflammation and onset
of ischemic events.21,44 Leukocyte–platelet aggregates (LPAs)
in peripheral blood have been considered as a novel marker
of activated platelets,15 which possess the “bridge” effects
for other cells in vasculature, particularly leukocytes re-
cruited via platelet secretory components including several
chemokines and membrane ligands.21 The interplay of plate-
lets and leukocytes is primarily attributed to P-selectin,
an adhesive molecule reserved in platelet alpha-granules
and transported to the surface of activated platelets. The
pivotal receptor for P-selectin, P-selectin glycoprotein ligand-
1, is elementarily expressed on the membranes of most
leukocytes.45 Activated platelets also release a variety of
prothrombotic and proinflammatory mediators associ-
ated with leukocyte recruitment, including soluble CD40
ligand, regulated upon activation, normal T cell ex-
pressed and secreted (RANTES), and thromboxane A2.21
Moreover, the formation of LPA may contribute to
ischemia–reperfusion injury,23,24 which may be associ-
ated with the therapeutic effect of IVT. Kupatt et al46 have
proposed that LPAs have the properties to exaggerate
reperfusion injury by accumulating in blood vessels with
an ischemic event, and Ritter et al24 have found an ap-
proximately 2-fold increase in LPA after ischemic stroke
and reperfusion compared to preischemic values, leading
to microvascular plugging and decreased ischemia per-
fusion. In this process, leukocytes are recruited with platelet
aggregation and consumption. Thus, the PWR may rep-
resent the degree of inflammatory and thrombotic events,
and reflect the severity of ischemic stroke and progno-
sis of patients treated with IVT.
To our knowledge, this is the first study to calculate
the PWR and investigate the relationship between this
ratio and 90-day outcomes for AIS with IVT. The results
of our retrospective study indicate that a higher WBC
with a lower PLT on admission is associated with poorer
prognosis with respect to initial stroke severity (NIHSS
score) on admission and 90-day functional outcome (mRS
score). The results were suitably adjusted for several major
potential confounders, including age, sex, hypertension,
diabetes mellitus, CAD, smoking, drinking, hyperlipid-
emia, atrial fibrillation, prior stroke or TIA, prior drug
use, maintenance of the dose level of statin, OTT, stroke
subtype, hemorrhagic transformation, symptomatic ce-
rebral hemorrhage, baseline NIHSS score, BP, glucose,
creatinine, and blood lipid profiles. Moreover, our study
provides the best estimated cutoff value of PWR for pre-
diction of 90-day outcomes after AIS with thrombolytic
therapy. Also, there was an evident difference in the PWR
values between favorable and unfavorable outcomes in
PWR AS A PREDICTOR OF 90-DAY OUTCOME IN ISCHEMIC STROKE PATIENTS
patients with the LAA subtype. The predictive effect of
PWR on prognosis was independent of other risk factors
for ischemic stroke patients with IV rt-PA treatment, par-
ticularly LAA subtype.
The present study has several limitations. The sever-
ity of stroke is indicated by NIHSS score47 and infarct
volume.30 We only found a correlation between PWR and
NIHSS score, but an association between infarct volume
and PWR could not be evaluated because no infarct volume
measurements were made. Also, the limited sample size
may be a limitation to the variable screening for multi-
variate logistic regression and other statistical analyses,
in particular the comparison of mean PWR values among
stroke subtypes. It was determined that the 90-day out-
comes of the CE subtype were poorer than those of other
subtypes, whereas the PWR values of the CE subtype were
not significantly lower than those of the LAA or SVD
subtype. Further, we observed the difference in PWR values
between favorable and unfavorable outcomes for the LAA
subtype. This trend, however, cannot be accurately evalu-
ated in SVD and CE subtypes because of the sample-
size limitation. Moreover, some patients with prior
hemogram analysis in other hospitals on admission, would
not be drawn blood again and be excluded in the present
study, which may result in a selection bias for analysis.
In conclusion, our study agrees with the clinical im-
portance of PLT and WBC count in ischemic stroke with
IVT and shows for the first time a clear correlation between
PWR and initial stroke severity at the time of admis-
sion. The association between PWR and outcomes for
ischemic stroke is independent of other known predic-
tive factors; thus, the study of PWR may enable patients
to be identified at risk for future unfavorable prognosis.
This ratio, with an easy and routine measurement, may
be an early, convenient, and important predictor for the
prognosis of ischemic stroke, particularly the LAA stroke
subtype. The value of PWR in AIS with or without IVT
should be investigated in future prospective random-
ized controlled trials.
Acknowledgment: The present study was supported by the
Foundation of Wenzhou Municipal Science and Technology
Bureau (No. Y20130214).
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