Semin Thromb Hemost 2017; 43(06): 599-608
DOI: 10.1055/s-0037-1603360
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Can Mean Platelet Volume Be Used as a Predictor of Vascular Disease? Problems and Pitfalls

Deepa R. J. Arachchillage
1   Department of Haematology, Imperial College Healthcare NHS Trust and Imperial College London, London, United Kingdom
2   Department of Haematology, Royal Brompton Hospital, London, United Kingdom
,
Mike Laffan
1   Department of Haematology, Imperial College Healthcare NHS Trust and Imperial College London, London, United Kingdom
› Author Affiliations
Further Information

Publication History

Publication Date:
13 June 2017 (online)

Abstract

Platelets play a pivotal role in both hemostasis and thrombosis. Increased platelet volume has several etiologies and may be secondary to a genetic variant, platelet activation, increased platelet turnover, or in response to inflammatory stimuli. There are several hereditary syndromes in which an increased mean platelet volume (MPV) occurs in association with a reduction in platelet number and function. An acquired increase in platelet size is often associated with increased platelet reactivity, shortened bleeding time, and increased platelet aggregation. Many studies have shown that high MPV is associated with increased risk of venous and arterial thrombosis, but genome-wide association analyses found a weak inverse association between the risk of coronary heart disease and MPV. The disease associations of MPV suggest that it could provide a useful contribution to risk assessment algorithms for both venous thromboembolism and arterial thrombosis. However, owing to the problems associated with reliably assessing MPV, it does not yet constitute a practically useful biomarker for this purpose. Before MPV can be adopted for wider clinical use, the methodological problems involved in obtaining accurate and interlaboratory comparable results must be resolved. In particular, a major degree of standardization is required, as are local reference ranges calculated with respect to specified time intervals from venipuncture to laboratory analysis. We discuss here the potential role of MPV in predicting the risk of acquired thrombotic disorders in addition to roles in congenital thrombocytopenic disorders, as well as the problems and pitfalls associated with use of MPV in these settings.

Authors' Contribution

DRJ Arachchillage performed the literature search and wrote the first draft. M. Laffan reviewed the manuscript, and both authors approved the final manuscript.


 
  • References

  • 1 Davì G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007; 357 (24) 2482-2494
  • 2 Leslie M. Cell biology. Beyond clotting: the powers of platelets. Science 2010; 328 (5978): 562-564
  • 3 Noris P, Klersy C, Gresele P. , et al; Italian Gruppo di Studio delle Piastrine. Platelet size for distinguishing between inherited thrombocytopenias and immune thrombocytopenia: a multicentric, real life study. Br J Haematol 2013; 162 (01) 112-119
  • 4 Chu SG, Becker RC, Berger PB. , et al. Mean platelet volume as a predictor of cardiovascular risk: a systematic review and meta-analysis. J Thromb Haemost 2010; 8 (01) 148-156
  • 5 Papanas N, Symeonidis G, Maltezos E. , et al. Mean platelet volume in patients with type 2 diabetes mellitus. Platelets 2004; 15 (08) 475-478
  • 6 Nadar S, Blann AD, Lip GY. Platelet morphology and plasma indices of platelet activation in essential hypertension: effects of amlodipine-based antihypertensive therapy. Ann Med 2004; 36 (07) 552-557
  • 7 Kario K, Matsuo T, Nakao K. Cigarette smoking increases the mean platelet volume in elderly patients with risk factors for atherosclerosis. Clin Lab Haematol 1992; 14 (04) 281-287
  • 8 Noris P, Klersy C, Zecca M. , et al. Platelet size distinguishes between inherited macrothrombocytopenias and immune thrombocytopenia. J Thromb Haemost 2009; 7 (12) 2131-2136
  • 9 Lippi G, Pavesi F, Pipitone S. Evaluation of mean platelet volume with four hematological analyzers: harmonization is still an unresolved issue. Blood Coagul Fibrinolysis 2015; 26 (02) 235-237
  • 10 Senaran H, Ileri M, Altinbaş A. , et al. Thrombopoietin and mean platelet volume in coronary artery disease. Clin Cardiol 2001; 24 (05) 405-408
  • 11 Park Y, Schoene N, Harris W. Mean platelet volume as an indicator of platelet activation: methodological issues. Platelets 2002; 13 (5–6): 301-306
  • 12 Schoorl M, Schoorl M, Oomes J, van Pelt J. New fluorescent method (PLT-F) on Sysmex XN2000 hematology analyzer achieved higher accuracy in low platelet counting. Am J Clin Pathol 2013; 140 (04) 495-499
  • 13 Briggs C, Harrison P, Machin SJ. Continuing developments with the automated platelet count. Int J Lab Hematol 2007; 29 (02) 77-91
  • 14 Seo JY, Lee ST, Kim SH. Performance evaluation of the new hematology analyzer Sysmex XN-series. Int J Lab Hematol 2015; 37 (02) 155-164
  • 15 Balduini CL, Pecci A, Noris P. Inherited thrombocytopenias: the evolving spectrum. Hamostaseologie 2012; 32 (04) 259-270
  • 16 Noris P, Perrotta S, Bottega R. , et al. Clinical and laboratory features of 103 patients from 42 Italian families with inherited thrombocytopenia derived from the monoallelic Ala156Val mutation of GPIbα (Bolzano mutation). Haematologica 2012; 97 (01) 82-88
  • 17 Machin SJ, Briggs C. Mean platelet volume: a quick, easy determinant of thrombotic risk?. J Thromb Haemost 2010; 8 (01) 146-147
  • 18 Latger-Cannard V, Hoarau M, Salignac S, Baumgart D, Nurden P, Lecompte T. Mean platelet volume: comparison of three analysers towards standardization of platelet morphological phenotype. Int J Lab Hematol 2012; 34 (03) 300-310
  • 19 Bowles KM, Cooke LJ, Richards EM, Baglin TP. Platelet size has diagnostic predictive value in patients with thrombocytopenia. Clin Lab Haematol 2005; 27 (06) 370-373
  • 20 Patterson K. Platelet parameters generated by automated blood counters. CME Bulletin Haematology 1997; 1: 13-16
  • 21 Trowbridge EA, Reardon DM, Hutchinson D, Pickering C. The routine measurement of platelet volume: a comparison of light-scattering and aperture-impedance technologies. Clin Phys Physiol Meas 1985; 6 (03) 221-238
  • 22 Harrison P, Mackie I, Mumford A. , et al; British Committee for Standards in Haematology. Guidelines for the laboratory investigation of heritable disorders of platelet function. Br J Haematol 2011; 155 (01) 30-44
  • 23 Lancé MD, van Oerle R, Henskens YM, Marcus MA. Do we need time adjusted mean platelet volume measurements?. Lab Hematol 2010; 16 (03) 28-31
  • 24 Pantanowitz L, Wiley CA, Demetris A. , et al. Experience with multimodality telepathology at the University of Pittsburgh Medical Center. J Pathol Inform 2012; 3: 45
  • 25 Billard M, Lainey E, Armoogum P, Alberti C, Fenneteau O, Da Costa L. Evaluation of the CellaVision DM automated microscope in pediatrics. Int J Lab Hematol 2010; 32 (05) 530-538
  • 26 Rollins-Raval MA, Raval JS, Contis L. Experience with CellaVision DM96 for peripheral blood differentials in a large multi-center academic hospital system. J Pathol Inform 2012; 3: 29
  • 27 Harrison P, Goodall AH. Studies on mean platelet volume (MPV)—new editorial policy. Platelets 2016; 27 (07) 605-606
  • 28 Levin J, Bessman JD. The inverse relation between platelet volume and platelet number. Abnormalities in hematologic disease and evidence that platelet size does not correlate with platelet age. J Lab Clin Med 1983; 101 (02) 295-307
  • 29 Bessman JD, Williams LJ, Gilmer Jr PR. Mean platelet volume. The inverse relation of platelet size and count in normal subjects, and an artifact of other particles. Am J Clin Pathol 1981; 76 (03) 289-293
  • 30 Klovaite J, Benn M, Yazdanyar S, Nordestgaard BG. High platelet volume and increased risk of myocardial infarction: 39,531 participants from the general population. J Thromb Haemost 2011; 9 (01) 49-56
  • 31 Biino G, Portas L, Murgia F. , et al. A population-based study of an Italian genetic isolate reveals that mean platelet volume is not a risk factor for thrombosis. Thromb Res 2012; 129 (04) e8-e13
  • 32 Vasse M, Masure A, Lenormand B. Mean platelet volume is highly correlated to platelet count. Thromb Res 2012; 130 (03) 559-560
  • 33 Panova-Noeva M, Schulz A, Hermanns MI. , et al. Sex-specific differences in genetic and nongenetic determinants of mean platelet volume: results from the Gutenberg Health Study. Blood 2016; 127 (02) 251-259
  • 34 Johnson M, Ramey E, Ramwell PW. Sex and age differences in human platelet aggregation. Nature 1975; 253 (5490): 355-357
  • 35 Stevens RF, Alexander MK. A sex difference in the platelet count. Br J Haematol 1977; 37 (02) 295-300
  • 36 Slavka G, Perkmann T, Haslacher H. , et al. Mean platelet volume may represent a predictive parameter for overall vascular mortality and ischemic heart disease. Arterioscler Thromb Vasc Biol 2011; 31 (05) 1215-1218
  • 37 Lozano M, Narváez J, Faúndez A. , et al. [Platelet count and mean platelet volume in the Spanish population] [in Spanish]. Med Clin (Barc) 1998; 110 (20) 774-777
  • 38 Braekkan SK, Mathiesen EB, Njølstad I, Wilsgaard T, Størmer J, Hansen JB. Mean platelet volume is a risk factor for venous thromboembolism: the Tromsø Study, Tromsø, Norway. J Thromb Haemost 2010; 8 (01) 157-162
  • 39 Santimone I, Di Castelnuovo A, De Curtis A. , et al; MOLI-SANI Project Investigators. White blood cell count, sex and age are major determinants of heterogeneity of platelet indices in an adult general population: results from the MOLI-SANI project. Haematologica 2011; 96 (08) 1180-1188
  • 40 Demirin H, Ozhan H, Ucgun T. , et al. Normal range of mean platelet volume in healthy subjects: insight from a large epidemiologic study. Thromb Res 2011; 128 (04) 358-360
  • 41 Lippi G, Meschi T, Borghi L. Mean platelet volume increases with aging in a large population study. Thromb Res 2012; 129 (04) e159-e160
  • 42 Karpatkin S, Khan Q, Freedman M. Heterogeneity of platelet function. Correlation with platelet volume. Am J Med 1978; 64 (04) 542-546
  • 43 Pathansali R, Smith NM, Bath PM. Prothrombotic megakaryocyte and platelet changes in hypertension are reversed following treatment: a pilot study. Platelets 2001; 12 (03) 144-149
  • 44 Breimo ES, Østerud B. Studies of biological functions in blood cells from individuals with large platelets. Platelets 2003; 14 (7-8): 413-419
  • 45 Martin JF, Trowbridge EA, Salmon G, Plumb J. The biological significance of platelet volume: its relationship to bleeding time, platelet thromboxane B2 production and megakaryocyte nuclear DNA concentration. Thromb Res 1983; 32 (05) 443-460
  • 46 Sharp DS, Bath PM, Martin JF, Beswick AD, Sweetnam PM. Platelet and erythrocyte volume and count: epidemiological predictors of impedance measured ADP-induced platelet aggregation in whole blood. Platelets 1994; 5 (05) 252-257
  • 47 Martin JF, Shaw T, Heggie J, Penington DG. Measurement of the density of human platelets and its relationship to volume. Br J Haematol 1983; 54 (03) 337-352
  • 48 Vizioli L, Muscari S, Muscari A. The relationship of mean platelet volume with the risk and prognosis of cardiovascular diseases. Int J Clin Pract 2009; 63 (10) 1509-1515
  • 49 Larsen SB, Grove EL, Hvas AM, Kristensen SD. Platelet turnover in stable coronary artery disease—influence of thrombopoietin and low-grade inflammation. PLoS One 2014; 9 (01) e85566
  • 50 Brown AS, Hong Y, de Belder A. , et al. Megakaryocyte ploidy and platelet changes in human diabetes and atherosclerosis. Arterioscler Thromb Vasc Biol 1997; 17 (04) 802-807
  • 51 Osselaer JC, Jamart J, Scheiff JM. Platelet distribution width for differential diagnosis of thrombocytosis. Clin Chem 1997; 43 (6 Pt 1): 1072-1076
  • 52 Budak YU, Polat M, Huysal K. The use of platelet indices, plateletcrit, mean platelet volume and platelet distribution width in emergency non-traumatic abdominal surgery: a systematic review. Biochem Med (Zagreb) 2016; 26 (02) 178-193
  • 53 Gieger C, Radhakrishnan A, Cvejic A. , et al. New gene functions in megakaryopoiesis and platelet formation. Nature 2011; 480 (7376): 201-208
  • 54 Lentaigne C, Freson K, Laffan MA, Turro E, Ouwehand WH. ; BRIDGE-BPD Consortium and the ThromboGenomics Consortium. Inherited platelet disorders: toward DNA-based diagnosis. Blood 2016; 127 (23) 2814-2823
  • 55 Soranzo N, Rendon A, Gieger C. , et al. A novel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function. Blood 2009; 113 (16) 3831-3837
  • 56 Meisinger C, Prokisch H, Gieger C. , et al. A genome-wide association study identifies three loci associated with mean platelet volume. Am J Hum Genet 2009; 84 (01) 66-71
  • 57 Noris P, Melazzini F, Balduini CL. New roles for mean platelet volume measurement in the clinical practice?. Platelets 2016; 27 (07) 607-612
  • 58 Demirtunc R, Duman D, Basar M. Effects of doxazosin and amlodipine on mean platelet volume and serum serotonin level in patients with metabolic syndrome: a randomised, controlled study. Clin Drug Investig 2007; 27 (06) 435-441
  • 59 Sivri N, Tekin G, Yalta K, Aksoy Y, Senen K, Yetkin E. Statins decrease mean platelet volume irrespective of cholesterol lowering effect. Kardiol Pol 2013; 71 (10) 1042-1047
  • 60 Coban E, Afacan B. The effect of rosuvastatin treatment on the mean platelet volume in patients with uncontrolled primary dyslipidemia with hypolipidemic diet treatment. Platelets 2008; 19 (02) 111-114
  • 61 Kucera M, Balaz D, Kruzliak P. , et al. The effects of atorvastatin treatment on the mean platelet volume and red cell distribution width in patients with dyslipoproteinemia and comparison with plasma atherogenicity indicators—a pilot study. Clin Biochem 2015; 48 (09) 557-561
  • 62 Briggs C, Kunka S, Hart D, Oguni S, Machin SJ. Assessment of an immature platelet fraction (IPF) in peripheral thrombocytopenia. Br J Haematol 2004; 126 (01) 93-99
  • 63 Pons I, Monteagudo M, Lucchetti G. , et al. Correlation between immature platelet fraction and reticulated platelets. Usefulness in the etiology diagnosis of thrombocytopenia. Eur J Haematol 2010; 85 (02) 158-163
  • 64 Wang C, Smith BR, Ault KA, Rinder HM. Reticulated platelets predict platelet count recovery following chemotherapy. Transfusion 2002; 42 (03) 368-374
  • 65 Sokolic R, Oden N, Candotti F. Assessment of immature platelet fraction in the diagnosis of Wiskott-Aldrich syndrome. Front Pediatr 2015; 3: 49
  • 66 Greene LA, Chen S, Seery C, Imahiyerobo AM, Bussel JB. Beyond the platelet count: immature platelet fraction and thromboelastometry correlate with bleeding in patients with immune thrombocytopenia. Br J Haematol 2014; 166 (04) 592-600
  • 67 Balduini CL, Savoia A. Genetics of familial forms of thrombocytopenia. Hum Genet 2012; 131 (12) 1821-1832
  • 68 Balduini CL, Pecci A, Savoia A. Recent advances in the understanding and management of MYH9-related inherited thrombocytopenias. Br J Haematol 2011; 154 (02) 161-174
  • 69 Savoia A, Pastore A, De Rocco D. , et al. Clinical and genetic aspects of Bernard-Soulier syndrome: searching for genotype/phenotype correlations. Haematologica 2011; 96 (03) 417-423
  • 70 Bader-Meunier B, Proulle V, Trichet C. , et al. Misdiagnosis of chronic thrombocytopenia in childhood. J Pediatr Hematol Oncol 2003; 25 (07) 548-552
  • 71 Noris P, Pecci A, Di Bari F. , et al. Application of a diagnostic algorithm for inherited thrombocytopenias to 46 consecutive patients. Haematologica 2004; 89 (10) 1219-1225
  • 72 Kunishima S, Yamada T, Hamaguchi M, Saito H. Bernard-Soulier syndrome due to GPIX W127X mutation in Japan is frequently misdiagnosed as idiopathic thrombocytopenic purpura. Int J Hematol 2006; 83 (04) 366-367
  • 73 Gunay-Aygun M, Zivony-Elboum Y, Gumruk F. , et al. Gray platelet syndrome: natural history of a large patient cohort and locus assignment to chromosome 3p. Blood 2010; 116 (23) 4990-5001
  • 74 Coppinger JA, Cagney G, Toomey S. , et al. Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions. Blood 2004; 103 (06) 2096-2104
  • 75 Gawaz M, Langer H, May AE. Platelets in inflammation and atherogenesis. J Clin Invest 2005; 115 (12) 3378-3384
  • 76 Cameron HA, Phillips R, Ibbotson RM, Carson PH. Platelet size in myocardial infarction. Br Med J (Clin Res Ed) 1983; 287 (6390): 449-451
  • 77 Martin JF, Plumb J, Kilbey RS, Kishk YT. Changes in volume and density of platelets in myocardial infarction. Br Med J (Clin Res Ed) 1983; 287 (6390): 456-459
  • 78 Bath P, Algert C, Chapman N, Neal B. ; PROGRESS Collaborative Group. Association of mean platelet volume with risk of stroke among 3134 individuals with history of cerebrovascular disease. Stroke 2004; 35 (03) 622-626
  • 79 Endler G, Klimesch A, Sunder-Plassmann H. , et al. Mean platelet volume is an independent risk factor for myocardial infarction but not for coronary artery disease. Br J Haematol 2002; 117 (02) 399-404
  • 80 Kiliçli-Camur N, Demirtunç R, Konuralp C, Eskiser A, Başaran Y. Could mean platelet volume be a predictive marker for acute myocardial infarction?. Med Sci Monit 2005; 11 (08) CR387-CR392
  • 81 Lippi G, Mattiuzzi C, Comelli I, Cervellin G. Mean platelet volume in patients with ischemic heart disease: meta-analysis of diagnostic studies. Blood Coagul Fibrinolysis 2013; 24 (02) 216-219
  • 82 Astle WJ, Elding H, Jiang T. , et al. The allelic landscape of human blood cell trait variation and links to common complex disease. Cell 2016; 167 (05) 1415-1429 .e19
  • 83 Rupa-Matysek J, Gil L, Wojtasińska E, Ciepłuch K, Lewandowska M, Komarnicki M. The relationship between mean platelet volume and thrombosis recurrence in patients diagnosed with antiphospholipid syndrome. Rheumatol Int 2014; 34 (11) 1599-1605
  • 84 Miyakis S, Lockshin MD, Atsumi T. , et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4 (02) 295-306
  • 85 Riedl J, Kaider A, Reitter EM. , et al. Association of mean platelet volume with risk of venous thromboembolism and mortality in patients with cancer. Results from the Vienna Cancer and Thrombosis Study (CATS). Thromb Haemost 2014; 111 (04) 670-678
  • 86 Lippi G, Buonocore R, Cervellin G. The mean platelet volume is decreased in patients diagnosed with venous thromboembolism in the emergency department. Semin Thromb Hemost 2016; 42 (06) 632-635
  • 87 Akan H, Güven N, Aydogdu I, Arat M, Beksaç M, Dalva K. Thrombopoietic cytokines in patients with iron deficiency anemia with or without thrombocytosis. Acta Haematol 2000; 103 (03) 152-156
  • 88 Buss DH, Cashell AW, O'Connor ML, Richards II F, Case LD. Occurrence, etiology, and clinical significance of extreme thrombocytosis: a study of 280 cases. Am J Med 1994; 96 (03) 247-253