COMMENTARY

Mean platelet volume: a quick, easy determinant of thromboticrisk?

S . J . MACHIN and C . BR I GGSDepartment of Haematology, University College London Hospitals, London, UK

To cite this article: Machin SJ, Briggs C. Mean platelet volume: a quick, easy determinant of thrombotic risk? J Thromb Haemost 2010; 8: 146–7.

See also Chu SG, Becker RC, Berger PB, Bhatt DL, Eikelboom JW, Konkle B, Mohler ER, Reilly MP, Berger JS. Mean platelet volume as a predictor of

cardiovascular risk: a systematic review and meta-analysis. This issue, pp 148–56; Brækkan SK, Mathiesen EB, Njølstad I, Wilsgaard T, Størmer J,

Hansen JB. Mean platelet volume is a risk factor for venous thromboembolism: the Tromsø Study. This issue, pp 157–62.

In developed countries, most hematology laboratories have

automated blood cell counters that provide a platelet count as

part of the full blood count. Platelets are counted by these

machinesusing anumberof different techniques and in addition

they provide derived indices relating to the size of platelets. The

most commonly available derived parameter is the mean

platelet volume (MPV), calculated by dividing the plateletcrit

(PCT) by the total number of platelets. This is analogous to the

calculation for the mean red cell volume (MCV), in which the

hematocrit is divided by the total red cell count. As the various

automated cell counters measure the platelet count using

differing technologies, the MPV normal range in femtoliters

(fl) varies significantly between methods [1].

In this issue of the Journal of Thrombosis and Haemostasis,

Braekken et al. [2] report a large population study from

Tromso, Norway, which shows that increasing levels of MPV

are a predictor for venous thromboembolism, in particular

unprovoked venous thromboembolism. Also in this issue of the

Journal, Chu et al. [3] present a systematic review and a meta-

analysis of the value of MPV as a predictor of cardiovascular

risk. They report that an elevated MPV is associated with

mortality after acute myocardial infarction and re-stenosis

following coronary angioplasty. They conclude that the MPV

is a potential useful prognostic biomarker in patients with

cardiovascular disease. The evidence presented in these two

articles demonstrates convincingly that an increased MPV is a

useful risk marker for the prediction of venous thromboem-

bolism and various types of arterial thrombosis.

Although the data presented suggest the MPV may poten-

tially be useful as a predictive marker, there are a number of

concerns related to the technological limitations and variations

in themeasurement of theMPV that need to be considered. It is

important that future studies carefully address these issues if

patients are to be risk stratified on the basis of the MPV over a

relatively narrow range of values.

Evidence that large platelets are hemostatically more active

than smaller platelets was first obtained from in vitro studies

reported 35 years ago and which suggested that large platelets

maybemore important functionally than smaller platelets [4].An

increase inMPVhas been observed in relation to disease over the

past 15 years or so. Typically the MPV has been used to help

diagnose the relatively rare congenital macro thrombocytopenic

disorders and to assess auto immune peripheral thrombocytope-

nias. An increase in MPV has also consistently been reported to

occur after myocardial infarction and cerebral infarction and to

be associated with smoking, obesity, hypertension and hyperlip-

idemia. An inverse relationship normally exists between MPV

and the platelet count within the normal range, which probably

contributes to the maintenance of normal hemostatic function.

Theplatelet parametersderivedby theautomatedcell counter

are highly specific to the individual technologies developed for

each type of analyzer. Thus, different normal ranges for the

MPV can result, influenced by factors such as the anticoagulant

used in thecollection tubeand thedelay in time fromsampling to

analysis; in particular ethylenediaminetetraacetic acid (EDTA)-

induced platelet swelling. Many multi-center/national clinical

trials use a centralized laboratory with postage of samples for

analysis of routine laboratory data resulting in significant

variations in the time between venepuncture andMPVanalysis.

If theMPV is to be reliably measured, the potential influence of

anticoagulant on the MPV must be carefully controlled, either

using an alternative anticoagulant (such as citrate) or standard-

izing the time delay between sampling and analysis. With

impedance counting, the MPV increases over time as platelets

swell in EDTA, with increases of 7.9% within 30 min having

been reported and an overall increase of 13.4% over 24 h,

although themajority of this increase occurs within the first 6 h

[5]. Conversely when MPV is measured by an optical light

scatter system derived from the modal platelet size, the MPV

decreases over time, possibly as a result of the dilution of

cytoplasmic contents leading to adecrease in light scatter [6].An

equation allowing for the correction of MPV over time from

venepuncture has been published [7], but this is not widely

used because of the unpredictability in the time taken to

equilibrate in individual samples.

Correspondence: Samuel Machin, University College London

Hospitals, Haematology, 60 Whitfield Street, London, UK, W1T 4EU.

Tel: +44 207 307 7406; fax: +44 207 255 2833.

E-mail: samuel.machin@ucl.ac.uk

Journal of Thrombosis and Haemostasis, 8: 146–147 DOI: 10.1111/j.1538-7836.2009.03673.x

� 2009 International Society on Thrombosis and Haemostasis

Many laboratories do not report the MPV to clinicians for

diagnostic purposes.There areanumberof reasons for this, such

as lack of standardization, the dependency of the results on the

age of sample and the range of measurement methods that can

give different results. For example, most impedance counters

have anupper threshold of size for platelets, usually between 24–

36 fl and the MPV calculation usually excludes larger platelets

outside of this upper cut off volume. All manufacturers provide

internal quality control material with assigned values to the

MPV but as far as we are aware there is currently no external

quality assurance scheme available for MPV analysis.

Larger platelets are probably younger, more reactive and

more thrombogenic. TheMPV could potentially provide useful

clinical informationandbebuilt intoariskassessmentalgorithm

for both venous thromboembolism and arterial thrombosis.

However, before it can be used in this way the methodological

problems involved in obtaining an accurate resultmust be taken

into consideration and carefully standardized. It is crucial that

local normal ranges are calculated with specific time intervals

from venepuncture to laboratory analysis established.

Over the past 20 years, platelet analyzers have developed

significantly although the same basic techniques (impedance

counting or an optical method) are unchanged. Additional

analyzer platelet-derived parameters have been developed, such

as the measurement of an immature platelet fraction [8], which

seemstobeequivalent toareticulatedplatelet count. Inaddition,

thederivedplatelet large cell ratio,whichallows thequantitation

of platelets above a certain minimum size threshold (approxi-

mately 12 fl),may provide information comparable to theMPV

[9]. Genomic–wide association studies (GWAS) have become

increasingly used to identify new susceptibility loci for multifac-

torialdisease [10]andhavebeencarriedoutonquantitative traits

related to thrombosis. Several correlated single-nucleotide

polymorphisms (SNPs) in the proximity of the hypothetical

gene FLJ 36031 on chromosome 7q22.3 were identified to be

associated with the MPV [11]. Other genes modulating MPV

levelshavealsobeen identified [12].The influenceof these loci on

thrombosis risk may be modest as the percentage of MPV

variance at these loci is quite low, only up to about 5%. Further

investigation will be required to assess the direct clinical

importance of these SNPs and this highlights further the need

to improve the accuracy of theMPVmeasurement.

The two current articles in Journal of Thrombosis and

Haemostasis clearly demonstrate that an increased MPV using

the criteria defined in their methodology is a risk factor for

venous thromboembolism and cardiovascular disease. There-

fore, theuseof theMPVshouldbe encouragedaspartof the risk

assessment protocol for patients who are potentially at risk of

these conditions. However, confounding variables in MPV

measurement, such as the delay after venepuncture before

analysis,must be clearly defined and standardized.Thedifferent

normal ranges for the types of instrument must also be taken

into consideration to allow comparison of clinical data. The

instrumentmanufacturersmust also bemademore aware of the

potential of this parameter for thrombosis risk assessment and

encourage the various external quality assessment schemes

throughout the world to look at instrument-specific MPV

analysis. Therefore, at the present timewewouldonly advise the

use of the MPV in epidemiologic studies or for clinical

assessment of thrombotic risk when a single type of analyzer is

used and the technical, including time from sampling, aspects of

analysis are carefully controlled. More widespread comparison

of MPV data is not presently helpful as it is still dependant on

careful control of the various variables discussed above.

Acknowledgements

The department receives an unrestricted educational grant

from Sysmex.

Disclosure of Conflict of Interests

The authors state that they have no conflict of interest.

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� 2009 International Society on Thrombosis and Haemostasis