What’s in a Number? Examining the Prognostic and Predictive Importance of Platelet Count in Patients With Essential Thrombocythemia

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  • 1 H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.
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Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by clonal overproduction of platelets and an increased risk of thrombohemorrhagic complications. Patients are risk stratified by driver mutation, age, and thrombotic history and treated to reduce the risk of thrombotic and hemorrhagic events. The significance of platelet number as a risk factor or treatment goal is unclear. Despite the preponderance of data failing to demonstrate an association, there exists a pervasive belief that higher platelet counts correlate with an increased thrombotic risk. In fact, the association between thrombocytosis and bleeding is more clearly supported. Variability in regional consensus guidelines contributes to the uncertainty. This article reviews the data that shed light on the importance of platelet count in patients with ET.

Submitted January 21, 2020; accepted for publication May 21, 2020.

Disclosures: The authors have disclosed that they have no financial interests, arrangements, or affiliations with the manufacturers of any products discussed in this article or their competitors

Correspondence: Andrew T. Kuykendall, MD, H. Lee Moffitt Cancer Center & Research Institute, 12902 USF Magnolia Drive, COB 7th Floor, Tampa, FL 33612. Email: Andrew.Kuykendall@moffitt.org
  • 1.

    Arber DA, Orazi A, Hasserjian R, . The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016;127:23912405.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Tefferi A, Barbui T. Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk-stratification and management. Am J Hematol 2019;94:133143.

  • 3.

    Barbui T, Vannucchi AM, Buxhofer-Ausch V, . Practice-relevant revision of IPSET-thrombosis based on 1019 patients with WHO-defined essential thrombocythemia. Blood Cancer J 2015;5:e369.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Haider M, Gangat N, Lasho T, . Validation of the revised International Prognostic Score of Thrombosis for Essential Thrombocythemia (IPSET-thrombosis) in 585 Mayo Clinic patients. Am J Hematol 2016;91:390394.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Lekovic D, Gotic M, Milic N, . The importance of cardiovascular risk factors for thrombosis prediction in patients with essential thrombocythemia. Med Oncol 2014;31:231.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Carobbio A, Finazzi G, Guerini V, . Leukocytosis is a risk factor for thrombosis in essential thrombocythemia: interaction with treatment, standard risk factors, and Jak2 mutation status. Blood 2007;109:23102313.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Carobbio A, Antonioli E, Guglielmelli P, . Leukocytosis and risk stratification assessment in essential thrombocythemia. J Clin Oncol 2008;26:27322736.

  • 8.

    Gangat N, Wolanskyj AP, Schwager SM, . Leukocytosis at diagnosis and the risk of subsequent thrombosis in patients with low-risk essential thrombocythemia and polycythemia vera. Cancer 2009;115:57405745.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Girodon F, Dutrillaux F, Broséus J, . Leukocytosis is associated with poor survival but not with increased risk of thrombosis in essential thrombocythemia: a population-based study of 311 patients. Leukemia 2010;24:900903.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    De Stefano V, Za T, Rossi E, . Leukocytosis is a risk factor for recurrent arterial thrombosis in young patients with polycythemia vera and essential thrombocythemia. Am J Hematol 2010;85:97100.

    • Search Google Scholar
    • Export Citation
  • 11.

    Carobbio A, Ferrari A, Masciulli A, . Leukocytosis and thrombosis in essential thrombocythemia and polycythemia vera: a systematic review and meta-analysis. Blood Adv 2019;3:17291737.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Pearson TC, Wetherley-Mein G. Vascular occlusive episodes and venous haematocrit in primary proliferative polycythaemia. Lancet 1978;2:12191222.

  • 13.

    Cortelazzo S, Viero P, Finazzi G, . Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia. J Clin Oncol 1990;8:556562.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Buxhofer-Ausch V, Steurer M, Sormann S, . Influence of platelet and white blood cell counts on major thrombosis—analysis from a patient registry in essential thrombocythemia. Eur J Haematol 2016;97:511516.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Schwarz J, Ovesná P, Černá O, . Thrombosis in thrombocythemic Ph-myeloproliferations is associated with higher platelet count prior to the event: results of analyses of prothrombotic risk factors from a registry of patients treated with anagrelide. Eur J Haematol 2016;96:98106.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Fox EA, Kahn SR. The relationship between inflammation and venous thrombosis. A systematic review of clinical studies. Thromb Haemost 2005;94:362365.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Roumen-Klappe EM, den Heijer M, van Uum SH, . Inflammatory response in the acute phase of deep vein thrombosis. J Vasc Surg 2002;35:701706.

  • 18.

    Hernandez-Boluda JC, Pereira A, Cervantes F, . Clinical evaluation of the European LeukemiaNet response criteria in patients with essential thrombocythemia treated with anagrelide. Ann Hematol 2013;92:771775.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Carobbio A, Thiele J, Passamonti F, . Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients. Blood 2011;117:58575859.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Alvarez-Larrán A, Cervantes F, Pereira A, . Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia. Blood 2010;116:12051210, quiz 1387.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Alvarez-Larrán A, Pereira A, Guglielmelli P, . Antiplatelet therapy versus observation in low-risk essential thrombocythemia with a CALR mutation. Haematologica 2016;101:926931.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Gugliotta L, Iurlo A, Gugliotta G, . Unbiased pro-thrombotic features at diagnosis in 977 thrombocythemic patients with Philadelphia-negative chronic myeloproliferative neoplasms. Leuk Res 2016;46:1825.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Di Nisio M, Barbui T, Di Gennaro L, . The haematocrit and platelet target in polycythemia vera. Br J Haematol 2007;136:249259.

  • 24.

    Campbell PJ, MacLean C, Beer PA, . Correlation of blood counts with vascular complications in essential thrombocythemia: analysis of the prospective PT1 cohort. Blood 2012;120:14091411.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Berk PD, Wasserman LR, Fruchtman SM, Goldberg JD. Treatment of polycythemia vera: a summary of clinical trials conducted by the Polycythemia Vera Study Group. In: Wasserman LR, Berk PD, Berlin NI. Polycythemia Vera and the Myeloproliferative Disorders. Philadelphia, PA: W.B. Saunders Company; 1995:166194.

    • Search Google Scholar
    • Export Citation
  • 26.

    Birgegård G, Besses C, Griesshammer M, . Treatment of essential thrombocythemia in Europe: a prospective long-term observational study of 3649 high-risk patients in the Evaluation of Anagrelide Efficacy and Long-term Safety study. Haematologica 2018;103:5160.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Cortelazzo S, Finazzi G, Ruggeri M, . Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 1995;332:11321136.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Alvarez-Larrán A, Pereira A, Cervantes F, . Assessment and prognostic value of the European LeukemiaNet criteria for clinicohematologic response, resistance, and intolerance to hydroxyurea in polycythemia vera. Blood 2012;119:13631369.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Adragna NC, Fonseca P, Lauf PK. Hydroxyurea affects cell morphology, cation transport, and red blood cell adhesion in cultured vascular endothelial cells. Blood 1994;83:553560.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Gladwin MT, Shelhamer JH, Ognibene FP, . Nitric oxide donor properties of hydroxyurea in patients with sickle cell disease. Br J Haematol 2002;116:436444.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Cokic VP, Beleslin-Cokic BB, Tomic M, . Hydroxyurea induces the eNOS-cGMP pathway in endothelial cells. Blood 2006;108:184191.

  • 32.

    Lockwood SY, Erkal JL, Spence DM. Endothelium-derived nitric oxide production is increased by ATP released from red blood cells incubated with hydroxyurea. Nitric Oxide 2014;38:17.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Gumiero D, Di Gennaro L, Nicolazzi MA, . Hydroxyurea-mediated release of nitric oxide in myeloproliferative neoplasms patients: effects on platelet-leukocyte interaction. J Clin Pharmacol 2015;55:11251130.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Harrison CN, Campbell PJ, Buck G, . Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med 2005;353:3345.

  • 35.

    Gisslinger H, Gotic M, Holowiecki J, . Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET study, a randomized controlled trial. Blood 2013;121:17201728.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Barbui T, Tefferi A, Vannucchi AM, . Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia 2018;32:10571069.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Mesa RA, Jamieson C, Bhatia R, . NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018. J Natl Compr Canc Netw 2017;15:11931207.

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