Studies on Mean Platelet Volume (MPV) – New Editorial Policy

In this issue we highlight a very topical and timely review by Noris and colleagues entitled “New roles for MPV measurement in clinical practice? ” [1], and discuss our newly proposed editorial policy for the minimum requirements for future manuscripts that include MPV measurement as their major focus. Fast, precise and reliable measurement of platelet number and size was revolutionized in the 1970s by the widespread availability of automated full blood counters that utilise the aperture impedance or “Coulter” principle that was invented 20 years earlier [2]. As a consequence MPV became an additional parameter of interest to both clinicians and researchers and is routinely available on most modern analysers. One of the fascinating aspects of the normal platelet volume distribution is the classical log-normal distribution demonstrating the heterogeneity of platelet size [3]. This also led to the discovery of the inverse relationship between platelet count and MPV that seems to maintain a remarkably tight control on the total platelet mass between individuals. Having defined normality it soon then became apparent that changes in MPV are associated with both acquired and inherited forms of thrombocytopenia. Noris et al discuss how abnormalities in platelet size using MPV are indeed useful for studying and differentiating between inherited forms of macrothrombocytopenia and giant platelet syndromes from other inherited conditions, and from acquired thrombocytopenias [1,4]. However, as they point out, the majority of manuscripts on MPV (1313 papers in Pubmed since 2013; 98 papers which have appeared in this journal since 2006) have focused on the association of MPV with many other clinical conditions such as ischaemic and thrombotic disorders, and their associated clinical outcomes [1]. Many studies have now shown that MPV is raised in patients with thrombosis and can often predict poor outcomes. Norris et al have highlighted a number of important questions. Firstly they question whether a raised MPV is the possible cause of thrombosis or a consequence of the condition, for while there is sound evidence that MPV is influenced by genetic polymorphisms [5], and lifestyle factors [6], these effects account for <20% of natural variation [5,6,7], MPV is also increased following platelet consumption and acceleration of platelet turnover in thrombotic conditions. Noris et al emphasize that the majority of studies were performed during the acute phase of thrombosis which makes these mechanisms highly credible. We would also add that inflammatory mediators, such as IL-6, that are often raised in acute or chronic conditions, may also feedback to the bone marrow, resulting in changes to the whole Megakaryocytic/Platelet axis, polyploidization and consequent thrombopoiesis with a shift towards a more prothrombotic phenotype and a higher MPV [8]. Despite these caveats, Noris et al have highlighted a number of population studies that indeed suggest a potential association between MPV and disease. An editorial by Lippi has also recently stated that “It is now undeniable that the assessment of platelet size should be regarded as a valuable tool for diagnosis and therapeutic monitoring of a wide spectrum of arterial and venous disorders” [7]. However, interpretation of these studies still requires a note of caution when we also take into consideration the importance of pre-analytical and analytical variables. The dynamic range of MPV is narrow and, outside of macrothrombocytopenia, observed differences between groups are small and the affected groups typically have MPVs that are within the normal range. Noris et al point out that such small differences between patients and controls could be easily masked by the variation due to inadequate standardization of measurements. Pre-analytical variables, such as the anticoagulant used, and the time between blood collection and measurement are known to significantly affect MPV measurements. Although EDTA is traditionally used and recommended for samples destined for blood counting it is well known that platelets collected into EDTA anticoagulants undergo time-dependent platelet swelling and activation [9]. It is therefore critical that in studies where EDTA is the anticoagulant the time delay between sampling and analysis is standardized in both the controls and test samples so that accurate comparisons can be made both within and between studies [10]. Alternative anticoagulants should also be considered; citrate or magnesium sulphate, in an attempt to minimise time-dependent swelling [11]. Even after controlling pre-analytical variables there are also significant differences in MPV values produced by different full blood counters; especially between those from different manufacturers [12]. All current manufacturers apart from Bayer use impedance technology to determine MPV. Although It is well known that impedance measurements perform well in both internal and external quality control (QC) schemes, there are currently no suitable QC materials available to determine both within and between instrument comparisons and long term performance of MPV measurements (Sam Machin, personal communication). It is therefore vital that any study comparing different patient groups utilises the same conditions and technology to measure platelet MPV and counts. This still makes inter-study comparisons difficult when different technologies have been used. Although we agree that clinical utility of MPV indeed has much potential beyond thrombocytopenia, for the measurement to be routinely adopted, standardization and guidelines are urgently required; Correspondence: Paul Harrison, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. E-mail: P.Harrison. 1@bham.ac. uk http://www.tandfonline. com/iplt ISSN: 0953-7104 (print), 1369-1635 (electronic)