Purpose of Review
Thrombocytosis is common to all myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis. Despite the traditionally held belief amongst many clinicians that thrombocytosis correlates with thrombosis risk, there is little evidence in the literature to support that claim. Herein we critically analyze the literature to better understand the relationship between thrombocytosis and risk of thrombosis in MPN.
Both retrospective and prospective studies argue against associations between thrombocytosis and risk of thrombosis in patients with ET and PV. Rather, most studies suggest that the presence of extreme thrombocytosis is instead associated with an increased risk of hemorrhagic events, a paradoxical phenomenon with important clinical implications.
Thrombosis risk has a multifactorial set of etiologies in MPNs. While qualitative abnormalities of the platelets may contribute, associations between platelet quantity and thrombosis risk are weak in MPN patients.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Ruggeri M, Tosetto A, Frezzato M, Rodeghiero F. The rate of progression to polycythemia vera or essential thrombocythemia in patients with erythrocytosis or thrombocytosis. Ann Intern Med. 2003;139(6):470–5.
Griesshammer M, Bangerter M, Sauer T, Wennauer R, Bergmann L, Heimpel H. Aetiology and clinical significance of thrombocytosis: analysis of 732 patients with an elevated platelet count. J Intern Med. 1999;245(3):295–300.
Varghese LN, et al. The thrombopoietin receptor: structural basis of traffic and activation by ligand, mutations, agonists, and mutated calreticulin. Front Endocrinol (Lausanne). 2017;8:59.
Vannucchi AM, Barbui T. Thrombocytosis and thrombosis. Hematology Am Soc Hematol Educ Program. 2007;2007:363–70.
Skoda RC, Duek A, Grisouard J. Pathogenesis of myeloproliferative neoplasms. Exp Hematol. 2015;43(8):599–608.
James C, Ugo V, le Couédic JP, Staerk J, Delhommeau F, Lacout C, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434(7037):1144–8.
Pardanani AD, Levine RL, Lasho T, Pikman Y, Mesa RA, Wadleigh M, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood. 2006;108(10):3472–6.
Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006;3(7):e270.
Zoi K, Cross NCP. Genomics of myeloproliferative neoplasms. J Clin Oncol. 2017;35(9):947–54.
••Barbui T, et al. Development and validation of an International Prognostic Score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood. 2012;120(26):5128-33; quiz 5252. Practice-changing publication validating IPSET-thrombosis score for risk-stratifying patients with ET into three categories based on thrombotic risk.
Barbui T, Barosi G, Birgegard G, Cervantes F, Finazzi G, Griesshammer M, et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol. 2011;29(6):761–70.
Cortelazzo S, Viero P, Finazzi G, D'Emilio A, Rodeghiero F, Barbui T. Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia. J Clin Oncol. 1990;8(3):556–62.
Colombi M, Radaelli F, Zocchi L, Maiolo AT. Thrombotic and hemorrhagic complications in essential thrombocythemia. A retrospective study of 103 patients. Cancer. 1991;67(11):2926–30.
Bellucci S, Janvier M, Tobelem G, Flandrin G, Charpak Y, Berger R, et al. Essential thrombocythemias. Clinical evolutionary and biological data. Cancer. 1986;58(11):2440–7.
Campbell PJ, MacLean C, Beer PA, Buck G, Wheatley K, Kiladjian JJ, et al. Correlation of blood counts with vascular complications in essential thrombocythemia: analysis of the prospective PT1 cohort. Blood. 2012;120(7):1409–11.
Harrison CN. Management of essential thrombocythemia: implications of the medical research council primary thrombocythemia 1 trial. Semin Thromb Hemost. 2006;32(3):283–8.
Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, et al. Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients. Blood. 2011;117(22):5857–9.
••Barbui T, et al. Practice-relevant revision of IPSET-thrombosis based on 1019 patients with WHO-defined essential thrombocythemia. Blood Cancer J. 2015;5:e369 Practice-changing revision of well-established IPSET-thrombosis score used for thrombotic risk stratification in patients with ET.
••Haider M, et al. Validation of the revised International Prognostic Score of Thrombosis for Essential Thrombocythemia (IPSET-thrombosis) in 585 Mayo Clinic patients. Am J Hematol. 2016;91(4):390–4 External validation for revised IPSET-thrombosis score for patients with ET which is currently used in clinical practice.
•Gugliotta L, et al. Unbiased pro-thrombotic features at diagnosis in 977 thrombocythemic patients with Philadelphia-negative chronic myeloproliferative neoplasms. Leuk Res. 2016;46:18–25 Large cohort study assessing thrombotic risk factors, including platelet count, amongst Ph negative MPNs.
Carobbio A, Finazzi G, Antonioli E, Vannucchi AM, Barosi G, Ruggeri M, et al. Hydroxyurea in essential thrombocythemia: rate and clinical relevance of responses by European LeukemiaNet criteria. Blood. 2010;116(7):1051–5.
Hernandez-Boluda JC, et al. Clinical evaluation of the European LeukemiaNet response criteria in patients with essential thrombocythemia treated with anagrelide. Ann Hematol. 2013;92(6):771–5.
Spivak JL. Polycythemia vera: myths, mechanisms, and management. Blood. 2002;100(13):4272–90.
Schafer AI. Molecular basis of the diagnosis and treatment of polycythemia vera and essential thrombocythemia. Blood. 2006;107(11):4214–22.
Berk PD, Goldberg JD, Donovan PB, Fruchtman SM, Berlin NI, Wasserman LR. Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols. Semin Hematol. 1986;23(2):132–43.
Di Nisio M, et al. The haematocrit and platelet target in polycythemia vera. Br J Haematol. 2007;136(2):249–59.
Falanga A, Marchetti M. Thrombosis in myeloproliferative neoplasms. Semin Thromb Hemost. 2014;40(3):348–58.
Alvarez-Larran A, et al. Assessment and prognostic value of the European LeukemiaNet criteria for clinicohematologic response, resistance, and intolerance to hydroxyurea in polycythemia vera. Blood. 2012;119(6):1363–9.
Marchioli R, Finazzi G, Specchia G, Cacciola R, Cavazzina R, Cilloni D, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013;368(1):22–33.
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(4):778–82.
Cervantes F, Alvarez-Larrán A, Arellano-Rodrigo E, Granell M, Domingo A, Montserrat E. Frequency and risk factors for thrombosis in idiopathic myelofibrosis: analysis in a series of 155 patients from a single institution. Leukemia. 2006;20(1):55–60.
Elliott MA, Pardanani A, Lasho TL, Schwager SM, Tefferi A. Thrombosis in myelofibrosis: prior thrombosis is the only predictive factor and most venous events are provoked. Haematologica. 2010;95(10):1788–91.
Buxhofer-Ausch V, Gisslinger H, Thiele J, Gisslinger B, Kvasnicka HM, Müllauer L, et al. Leukocytosis as an important risk factor for arterial thrombosis in WHO-defined early/prefibrotic myelofibrosis: an international study of 264 patients. Am J Hematol. 2012;87(7):669–72.
Barosi G, Rosti V, Bonetti E, Campanelli R, Carolei A, Catarsi P, et al. Evidence that prefibrotic myelofibrosis is aligned along a clinical and biological continuum featuring primary myelofibrosis. PLoS One. 2012;7(4):e35631.
Kc D, Falchi L, Verstovsek S. The underappreciated risk of thrombosis and bleeding in patients with myelofibrosis: a review. Ann Hematol. 2017;96(10):1595–604.
Guglielmelli P, Carobbio A, Rumi E, de Stefano V, Mannelli L, Mannelli F, et al. Validation of the IPSET score for thrombosis in patients with prefibrotic myelofibrosis. Blood Cancer J. 2020;10(2):21.
Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, et al. Incidence and risk factors for bleeding in 1104 patients with essential thrombocythemia or prefibrotic myelofibrosis diagnosed according to the 2008 WHO criteria. Leukemia. 2012;26(4):716–9.
Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2017 update on diagnosis, risk-stratification, and management. Am J Hematol. 2017;92(1):94–108.
Koren-Michowitz M, Lavi N, Ellis MH, Vannucchi AM, Mesa R, Harrison CN. Management of extreme thrombocytosis in myeloproliferative neoplasms: an international physician survey. Ann Hematol. 2017;96(1):87–92.
•Chu DK, et al. Benefits and risks of antithrombotic therapy in essential thrombocythemia: a systematic review. Ann Intern Med. 2017;167(3):170–80 A recent meta-analysis suggesting unclear net benefit of antiplatelet therapy in patients with ET.
Alvarez-Larran A, Pereira A, Guglielmelli P, Hernandez-Boluda JC, Arellano-Rodrigo E, Ferrer-Marin F, et al. Antiplatelet therapy versus observation in low-risk essential thrombocythemia with a CALR mutation. Haematologica. 2016;101(8):926–31.
Larsen ML, Pedersen OH, Hvas AM, Niekerk PBK, Bønløkke S, Kristensen SD, et al. Once- versus twice-daily aspirin treatment in patients with essential thrombocytosis. Platelets. 2019;30(3):322–8.
•Roccsa B, et al. A randomized, double-blind trial of three aspirin regimens to optimize antiplatelet therapy in essential thrombocythemia. Blood. 2020; https://doi.org/10.1182/blood.2019004596. Important recent randomized study evaluating efficacy of different aspirin regimens in patients with ET.
Conflict of Interest
The authors declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Myeloproliferative Neoplasms
About this article
Cite this article
Galvez, C., Stein, B.L. Thrombocytosis and Thrombosis: Is There Really a Correlation?. Curr Hematol Malig Rep 15, 261–267 (2020). https://doi.org/10.1007/s11899-020-00588-z
- Myeloproliferative neoplasms
- Essential thrombocythemia
- Polycythemia vera