Thrombosis Research 128 (2011) 358–360

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Thrombosis Research

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Regular Article

Normal range of mean platelet volume in healthy subjects: Insight from a largeepidemiologic study

Hilmi Demirin a,1, Hakan Ozhan b,⁎,1, Taner Ucgun a,1, Ahmet Celer c,1, Sule Bulur d,1, Habip Cil e,1,Cemalettin Gunes f,1, Hayriye Ak Yildirim a,1

a Duzce University, Medical Faculty, Department of Biochemistry, Duzce, Turkeyb Duzce University, Medical Faculty, Department of Cardiology, Duzce, Turkeyc Duzce University, Medical Faculty, Department of Family Medicine, Duzce, Turkeyd Duzce University, Medical Faculty, Department of Physiology Duzce, Turkeye Dicle University, Medical Faculty, Department of Cardiology, Diyarbakir, Turkeyf Duzce University, Medical Faculty, Department of Pediatrics, Duzce, Turkey

Abbreviation: MPV, mean platelet volume.⁎ Corresponding author at: Duzce Universitesi Duzce

Duzce Turkey. Tel.: +90 532 558 28 73; fax: +90 380E-mail address: ozhanhakan@yahoo.com (H. Ozhan)

1 For the MELEN Investigators.

0049-3848/$ – see front matter © 2011 Elsevier Ltd. Aldoi:10.1016/j.thromres.2011.05.007

a b s t r a c t

a r t i c l e i n f o

Article history:

Received 16 February 2011Received in revised form 27 April 2011Accepted 5 May 2011Available online 28 May 2011

Keywords:Mean platelet volumeReference range

Aim:Mean platelet volume (MPV) in the healthy population has not been studied before. Therefore, the aim ofthe study was to measure MPV in normal subjects in a large cohort of Turkish adults.Methods: A total of 2298 subjects with a mean age of 50 (age range 18 to 92) were interviewed. Subjects whohad smoking habit, diabetes, hypertension, coronary artery disease, dyslipidemia, chronic obstructivepulmonary disease, cancer, chronic use of any drugs including antiplatelets, heavy drinkers, metabolicsyndrome, ejection fraction b55%, creatinine N1.4 in men and N1.1 in women, abnormal liver function testsand an abnormal TSH were excluded in a in a stepwise manner. Complete blood counts were done on thesame day within 6 hours by a CELL-DYN 3700 SL analyzer (Abbott Diagnostics).

Results: Three hundred twenty-six participants (204 females (63%) and 122 males (37%) with a mean age of41 ±16) constituted the final healthy cohort. Mean MPV of the cohort was 8.9±1.4 fL. There was nosignificant difference among age groups regarding MPV.Conclusion: Ninety-five percent of the individuals had a MPV between 7.2 and 11.7 fL. A patient having a MPVbeyond this range should be evaluated carefully especially for occlusive arterial diseases.

© 2011 Elsevier Ltd. All rights reserved.

1. Introduction

Platelets play a pivotal role in atherothrombosis, the major cause ofmost unstable coronary syndromes. Activation of platelets at the site ofvascular injury is themain pathogenesis of occlusive arterial disease [1].Platelets secrete and express a large number of substances that arecrucial mediators of coagulation, inflammation, thrombosis, andatherosclerosis [2]. The demonstrated ability of antiplatelet drugs toreduce cardiovascular events has reinforced themajor roleof platelets inthe atherothrombotic process [3].Circulating platelets vary in both sizeand functional activity. Larger platelets are probably younger, morereactive and producemore thrombogenic factors.Meanplatelet volume

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(MPV) is an indicator of platelet activation [4] and it has been reportedto increase in acute myocardial infarction and acute coronarysyndromes [5,6]. IncreasedMPV is also associatedwith highermortalityfollowing MI [6].

Although measurement of MPV produces clinically useful informa-tion, it remains a research tool that is yet to be included in routineclinical decision making. Although analyzed in automated machines,MPVmeasurement is anticoagulant and time dependent.MPV increasesover time as platelets swell in EDTA, therefore optimal MPV measure-ment should be within 2 hours of venipuncture [7]. In most of theinvestigations dealing with platelet reactivity, mean MPV of patientswere comparedwith the subjectswhowere admitted to the hospital butdid not have that specific disease [8]. These control groups werecollected from the patients who were admitted to the hospitals anddefinitely did not contain healthy subjects, causing a bias anduncertainty about the interpretation and clinical utility of the results.The results of epidemiologic studies will supply important support todefine the “real normal” range for that specific marker. Therefore, theaim of the current studywas to measure reference intervals of MPV in alarge cohort of Turkish adults.

Table 1Mean MPV and percentiles of MPV according to age groups.

Age groups Mean±SD(fL)

95% confidenceintervalfor the mean

Percentiles

Lowerbound

Upperbound

5 25 50 75 95

18-39 (n=196) 8.9±1.5 8.7 9.2 7.2 7.8 8.6 9.6 12.640-59 (n=80) 8.8±1.3 8.6 9.1 7.3 7.9 8.6 9.4 11.5N59 (n=50) 8.8±1.4 8.4 9.2 7.0 7.7 8.5 9.6 12.1

359H. Demirin et al. / Thrombosis Research 128 (2011) 358–360

2. Materials and Methods

2.1. Study Population

The MELEN Study is a prospectively designed survey on theprevalence of cardio metabolic risk factors in Turkish adults. Thebaseline visits were carried out in May and June, 2010 and biennialfollow-up visits were planned. The study was conducted in May andJune, 2010. Four-hundred subjects from each family physicianrepresentatively stratified for sex, age and for rural-urban distributionwere randomly assigned and invited to participate the study. A total of2298 subjects with a mean age of 50 (age range 18 to 92) wereinterviewed. The study protocol was approved by the EthicsCommittee of Duzce University and every subject signed a consentform. Data were obtained by a questionnaire, physical examination ofthe cardiovascular system, sampling of blood, recording of a restingelectrocardiogram, transthoracic echocardiographic examination,carotid-intima media thickness measurement, thyroid ultrasonogra-phy and respiratory function testing. Subjects who had smoking habit(389 participants), diabetes (292 participants), hypertension (648subjects), coronary artery disease (29 participants), dyslipidemia (54subjects), Chronic obstructive pulmonary disease (40 subjects),cancer (3 subjects), chronic use of any drugs including antiplatelettherapy (218 participants), heavy drinkers (31 subjects), metabolicsyndrome (214 subjects), ejection fraction b55% (7 subjects),creatinine N1.4 in men and N1.1 in women (19 participants),abnormal liver function tests (4 subjects) and an abnormal TSH (24subjects) were excluded in a in a stepwise manner. Subjects weredivided into 3 age groups as follows; group 1 (18–39), group 2(40–59), group 3 (N59).

2.2. Complete Blood Count Analysis

Two milliliters of blood were drawn into a vacutainer tubecontaining 0.04 ml of the 7.5% K3 salt of ethylenediaminetetraaceticacid (EDTA) from each subject. Complete blood counts were done onthe same day within 6 hours by a CELL-DYN 3700 SL analyzer (AbbottDiagnostics, Chicago, USA). Blood sampling was done in the earlymorning (all of the patients were requested to be fasting) between9:30–10:30 am and the samples were analyzed at 16:00 pm. Analysiswas measured duplicate in a random cohort of 20 participants. Intra-assay CV% variation was 2% for MPV and 4% for platelet count.

2.3. Definitions

Individuals with diabetes were diagnosed with criteria of theAmerican Diabetes Association [9] and metabolic syndrome wereidentified when 3 out of the 5 criteria of the National CholesterolEducation Program (ATP III) [10] weremet, modified for Turkish AdultRisk Factor study cut points [11]. Hypertension was defined as a bloodpressure 140 mmHg and/or 90 mmHg, and/or use of antihypertensivemedication. Coronary artery disease (CAD) was defined with thepresence of angina pectoris, a history of myocardial infarction with orwithout accompanying Minnesota codes of the ECG, or a history ofmyocardial revascularization. Heavy drinking was accepted as con-sumingN5 gr of alcohol daily. Chronic obstructive pulmonary diseasewas defined as having a history of the disease and havingbronchodilator and/or anti-inflammatory treatment.

2.4. Statistical Analyses

Statistical Package for Social Sciences software (SPSS 12, Chicago,IL, USA) was used for analysis. Descriptive parameters were shown asmean±standard deviation or in percentages. Student t-test andPearson's chi-square tests were used to analyze the differences inmeans and proportions between groups. Abnormally distributed

variables were compared using Mann-Whitney U test. A p valueofb0.05 was considered significant.

3. Results

Three hundred twenty-six participants (204 females (63%) and122 males (37%) with a mean age of 41±16) constituted the finalhealthy cohort. Mean blood pressure was 112±13 mmHg and bodymass indexwas 25±3. MeanMPV of the cohort was 8.9±1.4; min 6,4max 15.1 fL. Ninety -five percent of the individuals had a MPVbetween 7.2 and 11.7 fL. Mean platelet count was 258±62 109/L; min104, max 458 109/L. The percentiles and means of MPV according toage groups were given in Table 1. There was no significant differenceamong age groups regarding MPV or platelet count. Correlationanalysis revealed that there was a significant inverse relation betweenplatelet count andMPV (r=−0.33; pb0.001). Platelet count was alsoinversely correlated with hematocrit and hemoglobin (r=−0.16;p=0.004 and r=−0.19; p=0.001; respectively).

4. Discussion

The current study, for the first time in the literature set the normalrange of MPV in healthy subjects. The first mean of MPV was given byGiles et al. He recorded MPV in 5000 unselected blood specimens andshowed that 95% of adults who had been admitted to the hospital, ofwhich he had been affiliated, varied from 7 to 10.5 fl [12].

Platelet function and size correlate because larger platelets,produced from activated megakaryocytes in the bone marrow, arelikely to bemore reactive than normal platelets. Mean platelet volume(MPV) is a machine-calculated measurement of the average size ofplatelets. New platelets are larger, and an increasedMPV occurs whenincreased numbers of platelets are being produced. IncreasedMPV is areliable index of platelet activation and is a potentially useful markerin cardiovascular risk stratification [13]. Platelet activation as reflectedby elevated MPV may contribute to the pathogenesis of thrombosis-related complications in many diseases. Research related to theprognostic and diagnostic usefulness of MPV is still ongoing. Diagnosticperformance of MPV has been reported in different disease states; suchas need of severe oxygen support and/or low ph at birth [14] andinherited macrothrombocytopenias [15]. A MPV value ofN9 fL had 83%sensitivity and 43% specificity in the diagnosis of acute coronarysyndrome [16]. A MPV level of N11.3 fL was associated with asymp-tomatic coronary artery disease [17] and a level of N10.4 fL was apredictor of acute coronary syndrome in patients with acute chest pain[18]. A recently publishedmeta-analysis of 16 studies showed thatMPVwas higher in patients with AMI (9.2 fL) than in those without AMI(8.5 fL) [6]. Mean platelet volume has also prognostic capability. MPVcould predict impaired reperfusion (N9.05 fL) and no-reflow phenom-enon (N 10.3 fL) in patients with acute ST wave elevation myocardialinfarction [19,20]. Recently; prognostic value ofMPV has been validatedin patientswith decompensated heart failure (N 10.5 fL) and pulmonaryembolism (N10.9 fL) [21,22].

The cut off range of MPV in all of the different diseases mentionedabove ranged between 9 to 12.4 fL [6,14–22]. Concordant with the

360 H. Demirin et al. / Thrombosis Research 128 (2011) 358–360

literature data, the present study showed that 95% of the individualsreflecting a real population based healthy cohort, had a MPV of7.2 – 11.7 fL. In the current study, correlation analysis revealed thattherewas a significant inverse relation between platelet count andMPVwhich was well known [23]. Platelet count also showed a weak butsignificant inverse correlation with hematocrit and hemoglobin. Thiswas also shown before [24] but might have occurred by chance.

The most important problem about the clinical validity of MPV isthat it increases over time as platelets swell in EDTA, with an increaseof 7.9% within 30 min and an overall increase of 13.4% over 24 h butwith the majority of this increase occurring in the first 6 hours [25].Lancé et al. compared citrate and EDTA for the point of higheststability. They showed that platelets swell until 120 minutes in EDTAand until 60 minutes in citrate. They recommended an optimalmeasuring time of 120 minutes after venipuncture [7]. In the currentstudy, we could not achieve this time interval.

In conclusion, mean MPV in normal Turkish adults was 8.9±1.4.Ninety-five percent of the individuals had a MPV between 7.2 and11.7 fL. A patient having aMPV beyond this range should be evaluatedcarefully especially for occlusive arterial diseases.

4.1. Limitations of the Study

The results are valid for Caucasians. Further epidemiologicalstudies are needed to reveal exact normal reference ranges indifferent races and societies. The best time interval for MPVmeasurement is within 2 hours after venipuncture and this intervalcould not be achieved. Potential reasons for an increased plateletvolume other than platelet activation, such as inherited giant plateletdisorders, May Hegglin Syndrome, Mediterranean macrothrombocy-topenia, Bernard-Soulier syndrome etc. could not be differentiated.

Conflict of interest statement

None.

Funding source

This work was supported by the Duzce University Office ofScientific Investigations.

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