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

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Abstract

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.

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References

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  12. Hoffmann JJ. Reticulated platelets: analytical aspects and clinical utility. Clin Chem Lab Med. 2014;52:1107–17.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  20. Bowles KM, Warner BA, Baglin TP. Platelet mass has prognostic value in patients with myelodysplastic syndromes. Br J Haematol. 2006;135:198–200.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed  Google Scholar 

  24. Lucijanic M, Petrovecki M. Analysis of censored data. Biochem Med (Zagreb). 2012;22:151–5.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Lucijanic M, Skelin M, Lucijanic T. Survival analysis, more than meets the eye. Biochem Med (Zagreb). 2017;27:14–8.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Lucijanic M. Survival analysis in clinical practice: analyze your own data using an Excel workbook. Croat Med J. 2016;57:77–9.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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. 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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  35. Bellucci S, Harousseau JL, Brice P, Tobelem G. Treatment of essential thrombocythaemia By alpha 2a interferon. Lancet. 1988;332:960–1.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  41. Park Y, Schoene N, Harris W. Mean platelet volume as an indicator of platelet activation: methodological issues. Platelets. 2002;13:301–6.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Hematology Department, University Hospital Dubrava, Av. Gojka Suska 6, 10000, Zagreb, Croatia

    Marko Lucijanic, Zdravko Mitrovic, David Cicic, Zeljko Prka, Vlatko Pejsa & Rajko Kusec

  2. Division of Molecular Diagnosis and Genetics, Clinical Department of Laboratory Diagnostics, University Hospital Dubrava, Zagreb, Croatia

    Ana Livun & Rajko Kusec

  3. Department of Clinical Cytology and Cytometry, University Hospital Dubrava, Zagreb, Croatia

    Tajana Stoos-Veic

  4. Faculty of Medicine, University of Osijek, Osijek, Croatia

    Tajana Stoos-Veic

  5. School of Medicine, University of Zagreb, Zagreb, Croatia

    Zdravko Mitrovic, Vlatko Pejsa, Iva Lucijanic & Rajko Kusec

  6. Clinical Department of Laboratory Diagnostics, University Hospital Dubrava, Zagreb, Croatia

    Zeljko Romic & Marcela Zivkovic

  7. Radiology Department, General Hospital Dubrovnik, Dubrovnik, Croatia

    Zrinka Fabris

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  1. Marko Lucijanic
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  2. Zdravko Mitrovic
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Correspondence to Marko Lucijanic.

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

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Lucijanic, M., Mitrovic, Z., Cicic, D. et al. Increased mean platelet volume (MPV) is an independent predictor of inferior survival in patients with primary and secondary myelofibrosis. Int J Hematol 107, 166–172 (2018). https://doi.org/10.1007/s12185-017-2348-4

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  • DOI: https://doi.org/10.1007/s12185-017-2348-4

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