Incidence and Risk Factors Associated with Thrombosis at Presentation of Polycythemia Vera (PV)
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Abstract
Background
Polycythemia vera (PV) thromboembolism has a significant impact on morbidity and mortality, with a variety of risk factors.
Aims
To evaluate the incidence of thrombosis in PV patients, identify associated risk factors, and assess clinical outcomes, including thrombosis-free survival and overall survival (OS).
Methods
Data from Phramongkutklao Hospital (January 2000 to November 2023) were retrospectively analyzed. Patients diagnosed with PV (WHO 2022 criteria) were included, and demographic information, cardiovascular risk factors, thrombotic events, and laboratory data were collected.
Results
We enrolled 190 patients (73.68% male) with a mean age of 60.94±13.83 years and a median follow-up period of 3.13 years. Of these, 65.79% were classified as ELN high-risk. Thrombosis occurred in 67 patients (35.26%) either before or at PV diagnosis, with predominantly arterial. Key cardiovascular risk factors included hypertension (75.79%), dyslipidemia (56.84%), diabetes mellitus (50%), and smoking (34.74%). The JAK2V617F mutation was present in 73.16%. Mean hemoglobin was 18.08±1.84 g/dL; median WBC and platelet counts were 11,270/mm³ (IQR: 8,200-16,600) and 387,000/mm³ (IQR: 245,000-611,000), respectively. Multivariable analysis identified age ≥60 years (aOR 2.30; 95% CI: 1.21-4.38), female (aOR 1.60; 95% CI: 0.80-3.19), and WBC >11,000/mm³ (aOR 1.81; 95% CI: 0.96-3.41) as factors associated with thrombosis either before or at PV diagnosis. Post-diagnosis thrombosis occurred in 8.95%, with a 10-year cumulative incidence of 19.53%. Thrombosis-free survival and overall survival (OS) at 10 years were lower in the thrombosis group either before or at diagnosis group, at 59.65% vs. 76.71% (p=0.2037) and 67.06% vs. 87.54% (p=0.027), respectively.
Conclusions
The incidence of thrombosis occurring either before or at the time of PV diagnosis is consistent with findings from previous studies. Among the factors analyzed, age ≥60 years is the only statistically significant risk factor.
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
Loghavi S, Kanagal-Shamanna R, Khoury JD, Medeiros LJ, Naresh KN, Nejati R, et al. Fifth Edition of the World Health Classification of Tumors of the Hematopoietic and Lymphoid Tissue: Myeloid Neoplasms. Mod Pathol. 2024;37(2):100397.
Bewersdorf JP, How J, Masarova L, Bose P, Pemmaraju N, Mascarenhas J, et al. Moving toward disease modification in polycythemia vera. Blood. 2023;142(22):1859-70.
Tefferi A, Rumi E, Finazzi G, Gisslinger H, Vannucchi AM, Rodeghiero F, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia. 2013;27(9):1874-81.
Cerquozzi S, Barraco D, Lasho T, Finke C, Hanson CA, Ketterling RP, et al. Risk factors for arterial versus venous thrombosis in polycythemia vera: a single center experience in 587 patients. Blood Cancer J. 2017;7(12):662.
Griesshammer M, Kiladjian JJ, Besses C. Thromboembolic events in polycythemia vera. Ann Hematol. 2019;98(5):1071-82.
Cherdchoo N, Polprasert C, Rojnuckarin P, Kongkiatkamon S. Clinical characteristics and symptom burden of Thai myeloproliferative neoplasm patients. Hematology. 2023;28(1):2280731.
Elliott MA, Tefferi A. Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol. 2005;128(3):275-90.
Barbui T, Tefferi A, Vannucchi AM, Passamonti F, Silver RT, Hoffman R, et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia. 2018;32(5):1057-69.
Marchetti M, Vannucchi AM, Griesshammer M, Harrison C, Koschmieder S, Gisslinger H, et al. Appropriate management of polycythaemia vera with cytoreductive drug therapy: European LeukemiaNet 2021 recommendations. Lancet Haematol. 2022;9(4):e301-e311.
Suttantapidok S, Owattanapanich W. Clinical characteristics and outcomes of patients with polycythemia vera in Thailand: a single center study. J Hematol Transfus Med. 2021;31:57-64.
Khuhapinant A, Lertchaisataporn K, Phikulsod P, Siritanaratkul N. Incidence and Characteristics of Polycythemia Vera, Essential Thrombocythemia and Primary Myelofibrosis in Thailand: A 5-Year Retrospective Study. Blood. 2014;124(21):5563.
Polycythemia vera: the natural history of 1213 patients followed for 20 years. Gruppo Italiano Studio Policitemia. Ann Intern Med. 1995;123(9):656-64.
Barosi G, Birgegard G, Finazzi G, Griesshammer M, Harrison C, Hasselbalch H, et al. A unified definition of clinical resistance and intolerance to hydroxycarbamide in polycythaemia vera and primary myelofibrosis: results of a European LeukemiaNet (ELN) consensus process. Br J Haematol. 2010;148(6):961-63.
Finazzi G, low-dose aspirin in polycythemia (ECLAP). A prospective analysis of thrombotic events in the European collaboration study on low-dose aspirin in polycythemia (ECLAP). Pathol Biol (Paris). 2004;52(5):285-8.
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.
Chiaranairungrot K, Kaewpreechawat K, Sajai C, Pagowong N, Sukarat N, Piriyakhuntorn P, et al. Prevalence and clinical outcomes of polycythemia vera and essential thrombocythemia with hydroxyurea resistance or intolerance. Hematol Amst Neth. 2022;27(1):813-9.
Tefferi A, Elliott M. Thrombosis in myeloproliferative disorders: prevalence, prognostic factors, and the role of leukocytes and JAK2V617F. Semin Thromb Hemost. 2007;33(4):313-20.
Berlin NI. Diagnosis and classification of the polycythemias. Semin Hematol. 1975;12(4):339-51.
Anía BJ, Suman VJ, Sobell JL, Codd MB, Silverstein MN, Melton LJ. Trends in the incidence of polycythemia vera among Olmsted County, Minnesota residents, 1935-1989. Am J Hematol. 1994;47(2):89-93.
Stein BL, Williams DM, Wang NY, Rogers O, Isaacs MA, Pemmaraju N, et al. Sex differences in the JAK2 V617F allele burden in chronic myeloproliferative disorders. Haematologica. 2010;95(7):1090-7.
Landolfi R, Di Gennaro L, Nicolazzi MA, Giarretta I, Marfisi R, Marchioli R. Polycythemia vera: gender-related phenotypic differences. Intern Emerg Med. 2012;7(6):509-15.
Szuber N, Mudireddy M, Nicolosi M, Penna D, Vallapureddy RR, Lasho TL, et al. 3023 Mayo Clinic Patients With Myeloproliferative Neoplasms: Risk-Stratified Comparison of Survival and Outcomes Data Among Disease Subgroups. Mayo Clin Proc. 2019;94(4):599-610.
Kim J, Byun JM, Hong J, Koh Y, Shin DY, Kim I, et al. Incidence, characteristics and risk factors of thromboembolic events in East Asian patients with BCR-ABL1 negative myeloproliferative neoplasms. Sci Rep. 2021;11(1):17819.
Landolfi R, Di Gennaro L, Barbui T, De Stefano V, Finazzi G, Marfisi R, et al. Leukocytosis as a major thrombotic risk factor in patients with polycythemia vera. Blood. 2007;109(6):2446-52.
Carobbio A, Ferrari A, Masciulli A, Ghirardi A, Barosi G, Barbui T. Leukocytosis and thrombosis in essential thrombocythemia and polycythemia vera: a systematic review and meta-analysis. Blood Adv. 2019;3(11):1729-37.
Gerds AT, Mesa R, Burke JM, Grunwald MR, Stein BL, Squier P, et al. Association between elevated white blood cell counts and thrombotic events in polycythemia vera: analysis from REVEAL. Blood. 2024;143(16):1646-55.
Gu W, Zhang Y, Sun T, Ju M, Liu X, Xue F, et al. Prediction of thrombosis in polycythemia vera: Development and validation of a multiple factor-based prognostic score system. Res Pract Thromb Haemost. 2023;7(3):100132.
Marchioli R, Finazzi G, Specchia G, Masciulli A, Mennitto MR, Barbui T. The CYTO-PV: A Large-Scale Trial Testing the Intensity of CYTOreductive Therapy to Prevent Cardiovascular Events in Patients with Polycythemia Vera. Thrombosis. 2011;2011:794240.
Tefferi A, Barbui T. Polycythemia vera: 2024 update on diagnosis, risk-stratification, and management. Am J Hematol. 2023;98(9):1465-87.
Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet Lond Engl. 2005;365(9464):1054-61.
Pardanani A, Lasho TL, Finke C, Hanson CA, Tefferi A. Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera. Leukemia. 2007;21(9):1960-3.
Stevenson WS, Hoyt R, Bell A, Guipponi M, Juneja S, Grigg AP, et al. Genetic heterogeneity of granulocytes for the JAK2 V617F mutation in essential thrombocythaemia: implications for mutation detection in peripheral blood. Pathology (Phila). 2006;38(4):336-42.
Cerquozzi S, Tefferi A. Blast transformation and fibrotic progression in polycythemia vera and essential thrombocythemia: a literature review of incidence and risk factors. Blood Cancer J. 2015;5(11):e366.
Zhang Y, Zhou Y, Wang Y, Teng G, Li D, Wang Y, et al. Thrombosis among 1537 patients with JAK2V617F -mutated myeloproliferative neoplasms: Risk factors and development of a predictive model. Cancer Med. 2020;9(6):2096-105.
Guglielmelli P, Loscocco GG, Mannarelli C, Rossi E, Mannelli F, Ramundo F, et al. JAK2V617F variant allele frequency >50% identifies patients with polycythemia vera at high risk for venous thrombosis. Blood Cancer J. 2021;11(12):199.
Segura-Díaz A, Stuckey R, Florido Y, González-Martín JM, López-Rodríguez JF, Sánchez-Sosa S, et al. Thrombotic Risk Detection in Patients with Polycythemia Vera: The Predictive Role of DNMT3A/TET2/ASXL1 Mutations. Cancers. 2020;12(4):934.
Tefferi A, Guglielmelli P, Lasho TL, Coltro G, Finke CM, Loscocco GG, et al. Mutation-enhanced international prognostic systems for essential thrombocythaemia and polycythaemia vera. Br J Haematol. 2020;189(2):291-302.
Tefferi A, Lasho TL, Guglielmelli P, Finke CM, Rotunno G, Elala Y, et al. Targeted deep sequencing in polycythemia vera and essential thrombocythemia. Blood Adv. 2016;1(1):21-30.