International Journal of Hematology

, Volume 107, Issue 2, pp 166–172 | Cite as

Increased mean platelet volume (MPV) is an independent predictor of inferior survival in patients with primary and secondary myelofibrosis

  • Marko Lucijanic
  • Zdravko Mitrovic
  • David Cicic
  • Zeljko Prka
  • Vlatko Pejsa
  • Ana Livun
  • Tajana Stoos-Veic
  • Zeljko Romic
  • Marcela Zivkovic
  • Iva Lucijanic
  • Zrinka Fabris
  • Rajko Kusec
Original Article


Neoplastic megakaryopoiesis is a dominant feature of Philadelphia-chromosome-negative myeloproliferative neoplasms (Ph− MPNs), and elevated mean-platelet-volume (MPV) is a common finding in these diseases. The clinical and prognostic significances of MPV in patients with primary (PMF) and secondary myelofibrosis (SMF) have not been reported. We retrospectively analyzed 87 patients with myelofibrosis (66 with PMF, 21 with SMF) treated at our institution. MPV was recorded in addition to other hematological and clinical parameters. MPV was elevated in both PMF and SMF patients in comparison to controls, whereas there was no statistically significant difference between PMF and SMF. Elevated MPV was associated with lower platelets (P = 0.016), higher white blood cells (P = 0.015), higher percentage of circulatory blasts (P = 0.009), higher lactate dehydrogenase (P = 0.011), larger spleen size (P = 0.014) and higher Dynamic International Prognostic score category (P = 0.027), while there was no statistically significant association with driver mutations or degree of bone marrow fibrosis. Higher MPV was univariately associated with inferior overall survival in the whole cohort (HR = 3.82, P = 0.006), PMF (HR = 4.35, P = 0.007) and SMF patients (HR = 7.22, P = 0.034). These associations remained significant in multivariate analyses adjusted for DIPSS. Higher MPV is associated with more aggressive disease features and exhibits powerful independent prognostic properties in both PMF and SMF settings.


Philadelphia chromosome negative myeloproliferative neoplasm Primary myelofibrosis Mean platelet volume Survival 


Compliance with ethical standards

Conflict of interest

The authors report no conflicts of interest.

Ethical approval

The study was approved by the University Hospital Dubrava Review Board.

Informed consent

All subjects provided written informed consent for molecular studies.




  1. 1.
    Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.CrossRefPubMedGoogle Scholar
  2. 2.
    Buschle M, Janssen JW, Drexler H, Lyons J, Anger B, Bartram CR. Evidence for pluripotent stem cell origin of idiopathic myelofibrosis: clonal analysis of a case characterized by a N-ras gene mutation. Leukemia. 1988;2:658–60.PubMedGoogle Scholar
  3. 3.
    Barosi G, Mesa RA, Thiele J, Cervantes F, Campbell PJ, Verstovsek S, et al. Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the International Working Group for Myelofibrosis Research and Treatment. Leukemia. 2008;22:437–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Tefferi A, Lasho TL, Finke CM, Knudson RA, Ketterling R, Hanson CH, et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014;28:1472–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Hasselbalch HC. Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis: is chronic inflammation a trigger and driver of clonal evolution and development of accelerated atherosclerosis and second cancer? Blood. 2012;119:3219–25.CrossRefPubMedGoogle Scholar
  6. 6.
    Newberry KJ, Naqvi K, Nguyen KT, Cardenas-Turanzas M, Florencia Tanaka M, Pierce S, et al. Comorbidities predict worse prognosis in patients with primary myelofibrosis. Cancer. 2014;120:2996–3002.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009;113:2895–901.CrossRefPubMedGoogle Scholar
  8. 8.
    Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pereira A, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood. 2010;115:1703–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Martin JF, Shaw T, Heggie J, Penington DG. Measurement of the density of human platelets and its relationship to volume. Br J Haematol. 1983;54:337–52.CrossRefPubMedGoogle Scholar
  10. 10.
    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;32:443–60.CrossRefPubMedGoogle Scholar
  11. 11.
    Thompson CB, Eaton KA, Princiotta SM, Rushin CA, Valeri CR. Size dependent platelet subpopulations: relationship of platelet volume to ultrastructure, enzymatic activity, and function. Br J Haematol. 1982;50:509–19.CrossRefPubMedGoogle Scholar
  12. 12.
    Hoffmann JJ. Reticulated platelets: analytical aspects and clinical utility. Clin Chem Lab Med. 2014;52:1107–17.CrossRefPubMedGoogle Scholar
  13. 13.
    Chu SG, Becker RC, Berger PB, Bhatt DL, Eikelboom JW, Konkle B, et al. Mean platelet volume as a predictor of cardiovascular risk: a systematic review and meta-analysis. J Thromb Haemost. 2010;8:148–56.CrossRefPubMedGoogle Scholar
  14. 14.
    Kaya H, Kutay Yıldırımlı M, Kurt R, Beton O, Birhan Yilmaz M. Mean platelet volume as a predictor of heart failure-related hospitalizations in stable heart failure outpatients with sinus rhythm. Acta Cardiol Sin. 2017;33:292–300.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Kostrubiec M, Labyk A, Pedowska-Wloszek J, Hrynkiewicz-Szymanska A, Pacho S, Jankowski K, et al. Mean platelet volume predicts early death in acute pulmonary embolism. Heart. 2010;96:460–5.CrossRefPubMedGoogle Scholar
  16. 16.
    Tuncel T, Ozgun A, Emirzeoglu L, Celik S, Bilgi O, Karagoz B. Mean platelet volume as a prognostic marker in metastatic colorectal cancer patients treated with bevacizumab-combined chemotherapy. Asian Pac J Cancer Prev. 2014;15:6421–3.CrossRefPubMedGoogle Scholar
  17. 17.
    Lian L, Xia YY, Zhou C, Shen XM, Li XL, Han SG, et al. Mean platelet volume predicts chemotherapy response and prognosis in patients with unresectable gastric cancer. Oncol Lett. 2015;10:3419–24.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Rupa-Matysek J, Gil L, Kroll-Balcerzak R, Baranska M, Komarnicki M. Mean platelet volume as a predictive marker for venous thromboembolism and mortality in patients treated for diffuse large B-cell lymphoma. Hematol Oncol. 2016. doi: 10.1002/hon.2321.PubMedGoogle Scholar
  19. 19.
    Zhuang Q, Xiang L, Xu H, Fang F, Xing C, Liang B, et al. The independent association of mean platelet volume with overall survival in multiple myeloma. Oncotarget. 2016;7:62640–6.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Bowles KM, Warner BA, Baglin TP. Platelet mass has prognostic value in patients with myelodysplastic syndromes. Br J Haematol. 2006;135:198–200.CrossRefPubMedGoogle Scholar
  21. 21.
    Hacibekiroglu T, Akinci S, Basturk A, Inal B, Guney T, Bakanay SM, et al. Evaluation of inflammation parameters in philadelphia negative chronic myeloproliferative neoplasia patients. Asian Pac J Cancer Prev. 2015;16:5159–62.CrossRefPubMedGoogle Scholar
  22. 22.
    Kissova J, Bulikova A, Ovesna P, Bourkova L, Penka M. Increased mean platelet volume and immature platelet fraction as potential predictors of thrombotic complications in BCR/ABL-negative myeloproliferative neoplasms. Int J Hematol. 2014;100:429–36.CrossRefPubMedGoogle Scholar
  23. 23.
    Thiele J, Kvasnicka HM, Facchetti F, Franco V, van der Walt J, Orazi A. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica. 2005;90:1128–32.PubMedGoogle Scholar
  24. 24.
    Lucijanic M, Petrovecki M. Analysis of censored data. Biochem Med (Zagreb). 2012;22:151–5.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Lucijanic M, Skelin M, Lucijanic T. Survival analysis, more than meets the eye. Biochem Med (Zagreb). 2017;27:14–8.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Lucijanic M. Survival analysis in clinical practice: analyze your own data using an Excel workbook. Croat Med J. 2016;57:77–9.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Gangat N, Caramazza D, Vaidya R, George G, Begna K, Schwager S, et al. DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol. 2011;29:392–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Shah S, Mudireddy M, Barraco D, Hanson CA, Ketterling RP, Gangat N, et al. Marked elevation of serum lactate dehydrogenase (LDH) in primary myelofibrosis: clinical and prognostic correlates. Blood. 2016;128:3113.Google Scholar
  29. 29.
    Prajs I, Kuliczkowski K. Predictive factors of thrombosis for patients with essential thrombocythaemia: a single center study. Adv Clin Exp Med. 2017;26:115–21.CrossRefPubMedGoogle Scholar
  30. 30.
    Ayer M, Menken I, Yamak M, Ayer FA, Kirkizlar O, Burak Aktuglu M. The Impact of mean platelet volume (MPV) and JAK-2 mutation on thrombosis in chronic myeloproliferative diseases. Indian J Hematol Blood Transfus. 2017;33:181–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Cetin G, Ozkan T, Turgut S, Ali Cikrikcioglu M, Cem Ar M, Ayer M, et al. Evaluation of clinical and laboratory findings with JAK2 V617F mutation as an independent variable in essential thrombocytosis. Mol Biol Rep. 2014;41:6737–42.CrossRefPubMedGoogle Scholar
  32. 32.
    Arellano-Rodrigo E, Alvarez-Larran A, Reverter JC, Villamor N, Jou JM, Cervantes F. Automated assessment of the neutrophil and platelet activation status in patients with essential thrombocythemia. Platelets. 2012;23:336–43.CrossRefPubMedGoogle Scholar
  33. 33.
    Celik T, Unal S, Ekinci O, Ozer C, Ilhan G, Oktay G, et al. Mean platelet volume can predict cerebrovascular events in patients with sickle cell anemia. Pak J Med Sci. 2015;31:203–8.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Bellucci S, Ignatova E, Jaillet N, Boffa MC. Platelet hyperactivation in patients with essential thrombocythemia is not associated with vascular endothelial cell damage as judged by the level of plasma thrombomodulin, protein S, PAI-1, t-PA and vWF. Thromb Haemost. 1993;70:736–42.PubMedGoogle Scholar
  35. 35.
    Bellucci S, Harousseau JL, Brice P, Tobelem G. Treatment of essential thrombocythaemia By alpha 2a interferon. Lancet. 1988;332:960–1.CrossRefGoogle Scholar
  36. 36.
    Bellucci S, Legrand C, Boval B, Drouet L, Caen J. Studies of platelet volume, chemistry and function in patients with essential thrombocythaemia treated with Anagrelide. Br J Haematol. 1999;104:886–92.CrossRefPubMedGoogle Scholar
  37. 37.
    Yazici S, Yazici M, Erer B, Erer B, Calik Y, Ozhan H, et al. The platelet indices in patients with rheumatoid arthritis: mean platelet volume reflects disease activity. Platelets. 2010;21:122–5.CrossRefPubMedGoogle Scholar
  38. 38.
    Peng YF, Guo J, Deng YB. The role of mean platelet volume in patients with Takayasu arteritis. Ann Clin Biochem. 2017;54:273–8.CrossRefPubMedGoogle Scholar
  39. 39.
    Strati P, Bose P, Lyle L, Gaw K, Zhou L, Pierce SA, et al. Novel hematological parameters for the evaluation of patients with myeloproliferative neoplasms: the immature platelet and reticulocyte fractions. Ann Hematol. 2017;96:733–8.CrossRefPubMedGoogle Scholar
  40. 40.
    Alvarez-Larran A, Arellano-Rodrigo E, Reverter JC, Domingo A, Villamor N, Colomer D, et al. Increased platelet, leukocyte, and coagulation activation in primary myelofibrosis. Ann Hematol. 2008;87:269–76.CrossRefPubMedGoogle Scholar
  41. 41.
    Park Y, Schoene N, Harris W. Mean platelet volume as an indicator of platelet activation: methodological issues. Platelets. 2002;13:301–6.CrossRefPubMedGoogle Scholar
  42. 42.
    Qu XW, Rozenfeld RA, Huang W, Crawford SE, Gonzalez-Crussi F, Hsueh W. Interaction of platelet-activating factor, spleen and atrial natriuretic peptide in plasma volume regulation during endotoxaemia in rats. J Physiol. 1998;512(Pt 1):227–34.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Pyo JS, Sohn JH, Kang G. Diagnostic and prognostic roles of the mean platelet volume in malignant tumors: a systematic review and meta-analysis. Platelets. 2016;27:722–8.CrossRefPubMedGoogle Scholar
  44. 44.
    Sun XP, Li BY, Li J, Zhu WW, Hua Q. Impact of mean platelet volume on long-term mortality in chinese patients with ST-elevation myocardial infarction. Sci Rep. 2016;6:21350.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Barbui T, Carobbio A, Cervantes F, Vannucchi AM, Guglielmelli P, Antonioli E, et al. Thrombosis in primary myelofibrosis: incidence and risk factors. Blood. 2010;115:778–82.CrossRefPubMedGoogle Scholar
  46. 46.
    Lucijanic M, Pejsa V, Jaksic O, Mitrovic Z, Tomasovic-Loncaric C, Stoos-Veic T, et al. The degree of anisocytosis predicts survival in patients with primary myelofibrosis. Acta Haematol. 2016;136:98–100.CrossRefPubMedGoogle Scholar
  47. 47.
    Lucijanic M, Livun A, Tupek KM, Stoos-Veic T, Aralica G, Gecek I, et al. Heat shock protein 27 (HSP27/HSPB1) expression is increased in patients with primary and secondary myelofibrosis and may be affecting their survival. Leuk Lymphoma. 2017;58:2497–500.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  • Marko Lucijanic
    • 1
  • Zdravko Mitrovic
    • 1
    • 5
  • David Cicic
    • 1
  • Zeljko Prka
    • 1
  • Vlatko Pejsa
    • 1
    • 5
  • Ana Livun
    • 2
  • Tajana Stoos-Veic
    • 3
    • 4
  • Zeljko Romic
    • 6
  • Marcela Zivkovic
    • 6
  • Iva Lucijanic
    • 5
  • Zrinka Fabris
    • 7
  • Rajko Kusec
    • 1
    • 2
    • 5
  1. 1.Hematology DepartmentUniversity Hospital DubravaZagrebCroatia
  2. 2.Division of Molecular Diagnosis and Genetics, Clinical Department of Laboratory DiagnosticsUniversity Hospital DubravaZagrebCroatia
  3. 3.Department of Clinical Cytology and CytometryUniversity Hospital DubravaZagrebCroatia
  4. 4.Faculty of MedicineUniversity of OsijekOsijekCroatia
  5. 5.School of MedicineUniversity of ZagrebZagrebCroatia
  6. 6.Clinical Department of Laboratory DiagnosticsUniversity Hospital DubravaZagrebCroatia
  7. 7.Radiology DepartmentGeneral Hospital DubrovnikDubrovnikCroatia

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