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International Journal of Laboratory Hematology

The Official journal of the International Society for Laboratory Hematology

ORIGINAL ARTICLE INTERNAT IONAL JOURNAL OF LABORATO RY HEMATO LOGY

Association of mean platelet volume and platelet count with the


development and prognosis of ischemic and hemorrhagic stroke
J. DU* ,† , Q. WANG*, B. HE † , P. LIU † , J.-Y. CHEN † , H. QUAN*, X. MA*

*Department of Neurology, The S U M M A RY


Nuclear Industry 416 Hospital,
Chengdu, Sichuan, China Introduction: Mean platelet volume (MPV) and platelet (PLT) count

Department of Health and are the two major parameters that reflect the functions and activ-
Social Behavior, West China
School of Public Health, ities of PLTs. The associations of MPV and PLT count with the
Sichuan University, Chengdu, occurrence and prognosis of stroke have not been fully clarified.
Sichuan, China This study aimed to investigate the association of MPV and PLT
count with the development and prognosis of first-ever ischemic
Correspondence:
Prof. Xiao Ma, Ph.D., Depart- and hemorrhagic stroke in order to provide evidence for early diag-
ment of Health and Social nosis and treatment of both strokes.
Behavior, 17 South Renmin Methods: This study included 281 first-ever ischemic stroke and 164
Road, Section 3, West China first-ever hemorrhagic stroke patients between 2010 and 2012. All
School of Public Health,
Sichuan University, Chengdu, participants received routine blood tests within 2 h after admission
Sichuan 610041, China. and were categorized into good or poor prognosis group based on
Tel.: +862885422114; the Modified Rankin Scale (mRS) score. MPV and PLT counts were
Fax: +862885501295;
transformed into categorical variables and their association with
E-mail: maxiao8293846@
163.com the occurrence and prognosis of both strokes was evaluated by
multivariate logistic regression.
Results: The risk of ischemic and hemorrhagic stroke in MPV group
doi:10.1111/ijlh.12474 (>13 fL) was 22.17 and 5.21 times higher compared with normal
MPV group. The PLT count was positively correlated with the risk
Received 26 July 2015; accepted
of ischemic stroke, but negatively correlated with the risk of
for publication 31 December
2015 hemorrhagic stroke. MPV and PLT count was not correlated with
the prognosis of either stroke.
Keywords Conclusions: Increased MPV is an independent risk factor for both
Ischemic stroke, hemorrhagic strokes. Elevated PLT count increases the risk for ischemic stroke,
stroke, mean platelet volume, but decreases the risk for hemorrhagic stroke. However, neither
platelet count, prognosis
MPV nor PLT count has significant association with the prognosis
of either stroke.

is crucial in the development of ischemic stroke due


INTRODUCTION
to its participation in thromboemboli that may initiate
As a major component of the blood-vascular axis the symptoms of stroke [1, 2]. Activated PLTs initiate
responsible for preventing hemorrhage, platelet (PLT) the formation of a hemostatic plug and provide a scaf-

© 2016 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2016, 38, 233–239 233
234 J. DU ET AL. | MPV AND PLT COUNT IN STROKE

fold for the activation of coagulation [3, 4]. Moreover, treatment with lipid-lowering drugs, angiotensin-con-
PLT dysfunction has been found to be associated with verting enzyme inhibitors or anticoagulant drugs was
spontaneous intracerebral hemorrhage [5, 6]. The excluded from the study. All participants signed the
importance of abnormal PLT for the onset of acute informed consent, and the study was approved by the
cerebrovascular disorders has recently received ethical review committee of the hospital.
increasingly more attention [2, 7].
Mean platelet volume (MPV) and PLT count are
Collection of baseline characteristics, medical history,
the two major parameters that reflect the functions
and disease-related data
and activities of PLTs. MPV, which describes the mean
volume (size) of platelets, is an indicator that repre- The demographic and clinical characteristics were col-
sents megakaryocytic hyperplasia and metabolism, lected via a questionnaire, including the risk factors for
and platelet production in bone marrow, and indicates cardiovascular and cerebrovascular diseases, previous
the age of circulating platelets. MPV has been identi- disease history (hypertension, hyperlipemia, diabetes,
fied as an independent risk factor for cerebral infarc- and heart disease), and therapy. The cause of ischemic
tion [8], and a higher MPV is detected in patients stroke was categorized based on the Trial of Org 10172
with acute stroke, myocardial infarction, diabetes, in Acute Stroke Treatment (TOAST) rating system [13].
hypercholesterolemia as well as smokers compared The cerebral infarct size was measured at 3 days after
with normal subjects [8, 9]. PLT count is a parameter enrollment by computed tomography (CT) [14] or mag-
reflecting the production and aging of platelets [10]. netic resonance imaging (MRI) scan [15]. Those with
As two indicators that demonstrate platelet functions, the largest diameter of ≥3 cm were defined as large
MPV and PLT count have been reported to play infarcts, whereas those with the largest diameter of
important roles in the development and prognosis of <3 cm were considered as small infarcts. The intracere-
ischemic and hemorrhagic stroke [11, 12]. However, bral hemorrhage volume was determined using the for-
the associations of MPV and PLT count with the mula ABC/2 [16]. While a hemorrhage volume of
occurrence, severity and prognosis of stroke have not ≥30 mL indicated a large hemorrhage, while a volume
been fully clarified. of <30 mL was defined as a small hemorrhage. All mea-
In this case–control study, we evaluated the associ- surements were performed with a blind method.
ation of MPV and PLT count with the development
and prognosis of first-ever ischemic and hemorrhagic
Blood investigation
stroke to provide evidence for early diagnosis and
treatment of ischemic and hemorrhagic stroke, and to All subjects received routine blood testing within 2 h
improve their prognosis. after admission to the hospital. MPV and PLT count
were measured within 30 min after venipuncture with
a Sysmex XS-2000i autoanalyzer (Sysmex Corporation,
SUBJECTS AND METHODS
Kobe, Japan). The parameters were set according to
the index of adults in Sichuan province described in
Study subjects
National Guideline for Clinical Laboratory Procedures
Patients with first-ever ischemic or hemorrhagic stroke (Third Edition) [17].
who were admitted to our hospital between October
2010 and January 2012 were enrolled in this study.
Treatment of stroke
The average time elapsed from stroke onset to admis-
sion was 6 h. Subjects without any cardiovascular or The acute ischemic stroke patients without indications
cerebrovascular diseases who were admitted to our for thrombolysis were given aspirin at 300 mg/d for
hospital during the same time period were selected as 3 days, and 100 mg/d 3 days afterward. Those with
controls. Any subject with pregnancy, infection, reac- indications for thrombolytic therapy were given an
tive airway diseases, tumor, cerebral trauma, arteriove- intravenous injection of recombinant tissue-type plas-
nous malformation or bleeding caused by other factors, minogen activator (rTPA, 0.9 mg/kg) and long-term
inflammation, hematologic disease, or undergoing aspirin therapy (100 mg/d) at 24 h after thrombolysis.

© 2016 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2016, 38, 233–239
J. DU ET AL. | MPV AND PLT COUNT IN STROKE 235

The cardiogenic ischemic stroke patients with interna- surement data were presented as mean  standard
tional normalized ratio (INR) of 2–3 were given war- deviation (SD), and compared by t-tests. To evaluate
farin, and those rejecting determination of INR were the associations of MPV and PLT count with the
given aspirin (100 mg/d). Mannitol or furosemidum development and clinical outcome of stroke, MPV and
was given to lower the intracranial pressure. The hemor- PLT count were transformed into categorical variables
rhagic stroke patients with brainstem hemorrhage, cere- using the normal ranges of MPV (9.4–12.5 fL) and
bral hemorrhage of <30 mL, or cerebellar hemorrhage PLT (100–300 9 109/L) as the cutoff value [17], and
of <10 mL were intravenously injected with citicoline then included in a multivariate logistic regression
sodium (0.75 mg/d) for 10 days, and those with cerebral model. All statistical analyses were performed using
hemorrhage of >30 mL, cerebellar hemorrhage of SPSS version 16.0 (SPSS Inc., Chicago, IL, USA). A P
>10 mL or subarachnoid hemorrhage underwent surgi- value <0.05 was considered statistically significant.
cal therapy, mannitol or furosemidum treatment to
lower the intracranial pressure, and an intravenous
R E S U LT S
injection of citicoline sodium (0.75 mg/d), and vitamin
C (3 g/d) for 10 days. All patients with acute ischemic
General characteristics
stroke were intravenously administered with edaravone
at a daily dose of 60 mg 12 h apart for successive Based on the selection criteria, a total of 445 cases
10 days following admission. The patients with carotid were selected for the study including 281 cases of first-
artery plaques and/or low-density lipoprotein choles- ever ischemic stroke and 164 cases of first-ever hemor-
terol (LDL-C) concentration of >3.12 mmol/L were rhagic stroke. The general information of study sub-
orally given rosuvastatin at a daily dose of 10 mg. Anti- jects was summarized in Table 1. The mean age of the
hypertensive agents and antidiabetic drugs were given controls was similar to that of ischemic and hemor-
to lower blood pressure and blood glucose level. rhagic stroke patients (both P values >0.05). A higher
incidence of diabetes, hyperlipemia, and heart disease
was observed in ischemic stroke patients compared
Assessment of neurological impairment and clinical
with the controls (P < 0.05), whereas the prevalence
outcomes
of hypertension was significantly higher in hemor-
Neurological impairment at presentation was assessed rhagic stroke patients (75.6%) than that (45.5%) in
by the National Institutes of Health Stroke Scale the controls (v2 = 21.22, P < 0.001). Therefore, the
(NIHSS) [17], and the clinical outcomes were evalu- history of diabetes, hyperlipemia, and heart disease
ated with the Modified Rankin Scale (mRS) at 30 days was involved as confounding variables in the multi-
after treatment [18]. variate logistic regression model to evaluate the associ-
ation of MPV and PLT count with the development of
ischemic stroke, whereas history of hypertension was
Statistical analysis
used as a confounding variable in the regression analy-
Categorical variables were expressed as frequency and sis to assess the association of MPV and PLT count with
percentage, and analyzed by chi-square tests. Mea- the development of hemorrhagic stroke.

Table 1. Clinical characteristics of patients and control subjects

Control group Ischemic group P Hemorrhagic group P

No. 200 281 164


Age (years) 65.76  12.95 66.33  11.02 0.005 65.66  10.39 0.002
Male, n (%) 112 (56) 146 (52) 0.416 85 (51.8) 0.300
Diabetes, n (%) 39 (19.5) 117 (41.6) 0.000 39 (23.8) 0.412
Hyperlipidemia, n (%) 52 (26) 123 (43.8) 0.007 43 (26.2) 0.368
Heart disease, n (%) 34 (17) 92 (32.7) 0.000 31 (18.9) 0.389
Hypertension, n (%) 91 (45.5) 121 (43.1) 0.323 124 (75.6) 0.008

© 2016 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2016, 38, 233–239
236 J. DU ET AL. | MPV AND PLT COUNT IN STROKE

Of the 281 patients with ischemic stroke, 200 cases of ischemic (OR = 22.17; 95% CI, 7.86–62.53) and
were classified according to the TOAST system, hemorrhagic stroke (OR = 5.21; 95% CI, 1.62–16.74)
including 82 cases (41%) caused by large-artery in subjects with MPV of >12.5 fL as compared to those
atherosclerosis, 42 cases (21%) caused by small-vessel with normal range of MPV. In addition, the rise of
occlusion, 44 cases (22%) caused by cardioembolism, PLT count was found to increase the risk of ischemic
18 cases (9%) of other determined etiology, and 14 stroke (OR = 4.49; 95% CI, 1.49–13.53; P = 0.008),
cases (7%) of undetermined etiology. Cerebral infarct whereas the decrease of PLT count reduced the risk of
size was measured in 183 cases, including 114 cases hemorrhagic stroke (OR = 1.97; 95% CI, 1.08–3.62;
(62.3%) with small infarcts and 69 cases (37.7%) P = 0.03) (Table 2).
with large infarcts. Among the 164 hemorrhagic
stroke patients, intracerebral hemorrhage volume was
Changes of MPV, PLT count, and NIHSS score in ischemic
determined in 57 cases, including 27 cases (47.4%)
and hemorrhagic stroke patients with good and poor
with large hemorrhages and 30 cases (52.6%) with
prognosis
small hemorrhages.
The clinical outcomes were evaluated using the Modi-
fied Rankin Scale (mRS) at 30 days after treatment. Of
Association of MPV and PLT count with the development
the 281 ischemic stroke patients, 66 had no mRS scores,
of ischemic and hemorrhagic stroke
129 had good prognosis (<4), and 86 had poor prognosis
After the confounding factors were controlled, multi- (≥4). Among the 164 patients with hemorrhagic stroke,
variate logistic regression analysis revealed a reduction 31 had no mRS scores, 78 had good prognosis (<4), and
in the risk of ischemic (OR = 0.06; 95% CI, 0.02– 55 had poor prognosis (≥4). There were no significant
0.18) and hemorrhagic stroke (OR = 0.05; 95% CI, differences in gender, previous history of diabetes,
0.01–0.2) in subjects with MPV of <9.4 fL than those hyperlipidemia, hypertension, and heart diseases, alco-
with normal range of MPV and an increase in the risk hol consumption, or smoking between the subjects with

Table 2. Association of MPV and PLT count with the risk of ischemic and hemorrhagic stroke detected by
multivariate logistic regression analysis

No. cases No. cases


No. detected detected in
cases in ischemic hemorrhagic
in stroke stroke
Parameter controls subjects OR (95% CI)† P value subjects OR (95% CI)‡ P value

MPV (fL) Normal 109 128 1.00 – 88 1.00 –


range
(9.4–12.5)
Reduction 57 40 0.06 (0.02–0.18) <0.001 40 0.05 (0.01–0.20) <0.001
(<9)
Elevation 34 113 22.17 (7.86–62.53) <0.001 36 5.21 (1.62–16.74) 0.006
(>13)
PLT Normal 137 190 1.00 – 90 1.00 –
(9109/L) range
(100–300)
Reduction 29 31 0.76 (0.43–1.36) 0.36 42 1.97 (1.08–3.62) 0.03
(<100)
Elevation 34 60 4.49 (1.49–13.53) 0.008 32 1.42 (0.29–6.96) 0.66
(>300)

MPV, mean platelet volume; PLT, platelet.


†The controlled variables involve history of hyperlipidemia, diabetes, and heart diseases.
‡The controlled variable is history of hypertension.

© 2016 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2016, 38, 233–239
J. DU ET AL. | MPV AND PLT COUNT IN STROKE 237

poor and good prognoses (P > 0.05). MPV in the domly chosen for the known risk factors and com-
ischemic stroke patients with poor prognosis was signifi- pared with the control subjects with the same risk
cantly higher compared with those with good prognosis factors but without any defined vascular diseases.
(P < 0.01). However, no association was detected Our findings showed that a decline in MPV reduced
between PLT count and the prognosis of ischemic stroke the risk of ischemic stroke (OR = 0.06), whereas an ele-
(P = 0.051). In the hemorrhagic stroke patients, no cor- vated MPV increased the risk of ischemic stroke
relation was observed between MPV and PLT, and the (OR = 22.17). The elevation of MPV has been found to
prognosis (P = 0.14 and 0.15, respectively). The significantly increase the risk of ischemic stroke [20].
ischemic and hemorrhagic stroke patients with higher As an important indicator that describes platelet func-
pretreatment NIHSS scores were found to have a signifi- tion and activity, MPV is found to be positively associ-
cantly poorer prognosis (P < 0.001) (Table 3). There- ated with platelet reactivity. Large platelets, which
fore, NIHSS score, as a confounding variable, was contain more high-density granules and have higher
included in the multivariate logistic regression model to activity, are much easier to form thrombi [21, 22]. The
assess the associations of MPV and PLT count with the size of platelets is determined during the production of
prognosis of ischemic and hemorrhagic stroke. progenitor cells and does not change after being
released into the circulatory system. Therefore, the
hypercoagulable state caused by large platelets occurs
Association of MPV and PLT count with the prognosis of
before the onset of ischemic stroke [1]. Therefore, it
ischemic and hemorrhagic stroke
seems plausible to infer that the elevation of MPV may
After NIHSS score was controlled, no significant associa- increase the risk of ischemic stroke.
tion was detected between MPV and PLT count, and the To our knowledge, there are few reports evaluating
prognosis of ischemic and hemorrhagic stroke the role of MPV in hemorrhagic stroke. Currently, the
(P > 0.05). No analyses were performed due to too few association of MPV alteration with hemorrhagic stroke
cases with declined MPV or increased PLT count remains controversial. No clear association between
(Table 4). MPV and the risk of hemorrhagic stroke has been
detected in some studies [20, 23, 24]. Our findings
showed that the reduction of MPV may decrease the risk
DISCUSSION
of hemorrhagic stroke (OR = 0.05), whereas elevated
It has been known that platelets play an important MPV may increase the risk of hemorrhagic stroke
role in the pathophysiology of ischemic stroke by (OR = 5.214). It has been shown that the patients with
developing intravascular thrombus after erosion or reduced MPV have a higher likelihood of bleeding than
rupture of atherosclerotic plaques [1], while thrombo- those with elevated MPV, suggesting that MPV may be
cytopenia occurs concurrently with cerebral hemor- used to measure the tendency of bleeding, and serve as
rhage [19]. MPV and PLT count have been considered a parameter for assessing early-stage recovery of the
an index of the functions of platelets. In this study, hematopoietic function of bone marrow [25]. Neverthe-
281 patients with first-ever ischemic stroke and 164 less, it is possible that raised MPV is a response to bleed
patients with first-ever hemorrhagic stroke were ran- in the hemorrhagic cohort. In addition, the measure-

Table 3. Comparison of MPV, PLT count, and NIHSS score in ischemic and hemorrhagic stroke patients with good
or poor prognoses

Ischemic stroke Hemorrhagic stroke

Parameter Good prognosis Poor prognosis t P Good prognosis Poor prognosis t P

MPV 13.05  1.10 13.87  1.27 4.32 <0.001 12.23  1.25 12.63  0.75 1.50 0.14
PLT 174.89  75.49 151.13  64.83 1.96 0.051 148.93  83.83 126.18  49.74 1.47 0.15
NIHSS score 11.66  4.58 21.52  2.64 17.96 <0.001 12.48  5.07 20.41  3.62 7.16 <0.001

MPV, mean platelet volume; PLT, platelet; NIHSS, National Institutes of Health Stroke Scale.

© 2016 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2016, 38, 233–239
238 J. DU ET AL. | MPV AND PLT COUNT IN STROKE

Table 4. Association of MPV and PLT count with the prognosis in patients with ischemic and hemorrhagic stroke
assessed by multivariate logistic regression analysis

Ischemic stroke Hemorrhagic stroke

Good Poor OR Good Poor OR


Parameter prognosis prognosis (95% CI) P value prognosis prognosis (95% CI) P value

MPV (fL) Normal 64 49 1.00 – 39 21 1.00 –


range
(9.4–12.5)
Reduction 64 37 1.68 0.39 39 34 0.70 0.64
(<9) (0.51–5.54) (0.15–3.21)
Elevation 1 0 – – 0 0 – –
(>13)
PLT Normal 101 36 1.00 0.70 28 17 1.00 –
(9109/L) range
(100–300)
Reduction 26 48 1.41 47 38 1.03 0.97
(<100) (0.24–8.39) (0.28–3.81)
Elevation 2 2 – – 3 0 – –
(>300)

MPV, mean platelet volume; PLT, platelet.

ment of immature platelet fractions might provide addi- was correlated with the prognosis in patients with
tional value to this study. Further studies are needed to ischemic stroke, and those with elevated MPV had
investigate the role of MPV in hemorrhagic stroke and poorer outcomes. In addition, there was a significant dif-
the underlying mechanisms. ference in the degree of pretreatment neurological defi-
The present study demonstrated that a higher PLT cit between the patients with good and poor prognoses,
count increased the risk of ischemic stroke (OR = 4.49), and more severe neurological deficit was observed in
whereas lower PLT count reduced the risk of hemor- patients with poor prognosis, as shown by greater pre-
rhagic stroke (OR = 1.97). Aberrant elevation of PLT is treatment NIHSS score found in patients with poor prog-
found to promote thrombus formation, thereby nosis. A higher NIHSS score indicates a more severe
increasing the risk of ischemic stroke, while the aber- neurological deficit. It is therefore speculated that the
rant PLT reduction causes the impairment of coagula- association between elevated MPV and prognosis in
tion function, thereby resulting in cerebral patients with ischemic stroke may be affected by the
hemorrhage. It has been shown that increased capillary severity of pretreatment stroke. Our findings revealed
fragility and thrombocytopenia may occur concurrently no significant associations of MPV and PLT count with
with cerebral hemorrhage despite that the exact mech- the prognosis of ischemic and hemorrhagic stroke, after
anism of hemorrhage is unclarified [19]. the variable pretreatment NIHSS score was controlled.
The role of MPV and PLT count in the prognosis of This study was primarily limited by its small sample
stroke has not been elucidated. Elevated MPV has been size of some subgroups (e.g., subjects with elevated
shown to be associated with poor prognosis in patients MPV or PLT count). A larger sample with more evenly
with acute ischemic stroke [2, 26], but other studies distributed subjects across subgroups would have bene-
identified no significant correlation between MPV and fited our results. Furthermore, this study did not detect
the prognosis of stroke [27]. PLT count has been identi- the associations of MPV and PLT count with stroke
fied as a good predictor for hemorrhagic stroke-induced prognosis, which might be due to the limitation of sam-
death within 24 h of stroke onset, and significantly ple size. Further large scale, multicenter studies are
reduced PLT count is detected in ischemic stroke required to assess the role of MPV and PLT count in the
patients with poor prognosis or subjects who died of prognosis of stroke. Patients without any cardiovascular
ischemic stroke [28]. Our findings showed that MPV or cerebrovascular diseases who were admitted to our

© 2016 John Wiley & Sons Ltd, Int. Jnl. Lab. Hem. 2016, 38, 233–239
J. DU ET AL. | MPV AND PLT COUNT IN STROKE 239

hospital during the same time period were selected as stroke. Further studies are required to investigate the
controls. Another possible improvement to the study associations of MPV and PLT count with the prognosis
could have been mentioning the details for the reasons of ischemic and hemorrhagic stroke.
of their hospitalization and the treatment they received
before blood sample collection. In addition, MPV and
CONFLICT OF INTERESTS
PLT counts were transformed into categorical variables
in this study. It could be useful to find out whether the The authors declare no conflict of interests.
results are unchanged if continuous variables of MPV
and PLT count are used instead of categorical variables.
FUNDING
In summary, elevated MPV is an independent risk
factor of both ischemic and hemorrhagic stroke. Ele- Scientific Research Projects funded by the Department
vated PLT count is a risk factor of ischemic stroke, of Public Health of Sichuan Provine (Project No.
and reduced PLT count is a risk factor of hemorrhagic 100182).

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