Abstract
Patients with polycythemia vera (PV) or essential thrombocythemia (ET) presenting with splanchnic vein thrombosis (SVT) might have a specific clinico-biological profile. To investigate this hypothesis, 3705 PV/ET patients from three national registers, 118 of them presenting with SVT, were reviewed. After correction for age and sex, PV/ET patients with SVT showed an increased risk of death (HR 2.47, 95% CI 1.5–4.01, p < 0.001), venous thrombosis (IRR 3.4, 95%CI 2.1–5.5, p < 0.001), major bleeding (IRR 3.6, 95%CI 2.3–5.5, p < 0.001), and second cancer (IRR 2.37, 95%CI 1.4–4.1, p = 0.002). No case of acute leukemia was documented among patients with PV/ET presenting with SVT and seven of them (6%) progressed to myelofibrosis. SVT was not associated with lower risk of MF after correction by age and sex. Patients with SVT more frequently died from complications related to hepatic disease, major bleeding, or second cancer, resulting in a 5-year reduction of age- and sex-adjusted median survival. In conclusion, PV and ET patients presenting with SVT have shorter survival than patients with PV and ET of the same age and sex. This excess mortality is related to liver disease, major bleeding, and second cancer rather than to the natural evolution of the MPN.
References
Gruppo Italiano Studio Policitemia (1995) Polycythemia vera: the natural history of 1213 patients followed for 20 years. Gruppo Italiano Studio Policitemia. Ann Intern Med 123:656–664
Hultcrantz M, Kristinsson SY, Andersson TM, Landgren O, Eloranta S, Derolf AR, Dickman PW, Björkholm M (2012) Patterns of survival among patients with myeloproliferative neoplasms diagnosed in Sweden from 1973 to 2008: a population-based study. J Clin Oncol 30:2995–3001
Hultcrantz M, Björkholm M, Dickman PW, Landgren O, Derolf ÅR, Kristinsson SY et al (2018) Risk for arterial and venous thrombosis in patients with myeloproliferative neoplasms: a population-based cohort study. Ann Intern Med 168:317–325
Alvarez-Larrán A, Cervantes F, Bellosillo B, Giralt M, Juliá A, Hernández-Boluda JC, Bosch A, Hernández-Nieto L, Clapés V, Burgaleta C, Salvador C, Arellano-Rodrigo E, Colomer D, Besses C (2007) Essential thrombocythemia in young individuals: frequency and risk factors for vascular events and evolution to MF in 126 patients. Leukemia 21:1218–1223
Alvarez-Larrán A, Cervantes F, Pereira A, Arellano-Rodrigo E, Pérez-Andreu V, Hernández-Boluda JC et al (2010) Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia. Blood 116:1205–1210
Gangat N, Wolanskyj AP, Tefferi A (2006) Abdominal vein thrombosis in essential thrombocythemia: prevalence, clinical correlates, and prognostic implications. Eur J Haematol 77:327–333
Kiladjian JJ, Cervantes F, Leebeek FW, Marzac C, Cassinat B, Chevret S et al (2008) Relevance of the criteria commonly used to diagnose myeloproliferative disorder in patients with splanchnic vein thrombosis. Blood 111:4922–4929
Stein BL, Saraf S, Sobol U, Halpern A, Shammo J, Rondelli D, Michaelis L, Odenike O, Rademaker A, Zakarija A, McMahon B, Spivak JL, Moliterno AR (2013) Age-related differences in disease characteristics and clinical outcomes in polycythemia vera. Leuk Lymphoma 54:1989–1995
How J, Trinkaus KM, Oh ST (2018) Distinct clinical, laboratory and molecular features of myeloproliferative neoplasm patients with splanchnic vein thrombosis. Br J Haematol 183:310–313
Lavu S, Szuber N, Mudireddy M, Yogarajah M, Gangat N, Pardanani A, Hanson CA, Ketterling RP, Ashrani AA, Kamath PS, Tefferi A (2018) Splanchnic vein thrombosis in patients with myeloproliferative neoplasms: the Mayo clinic experience with 84 consecutive cases. Am J Hematol 93:E61–E64
Greenfield G, McMullin MF (2018) Splanchnic venous thrombosis in JAK2 V617F mutation positive myeloproliferative neoplasms - long term follow-up of a regional case series. Thromb J 16:33
Sant'Antonio E, Guglielmelli P, Pieri L, Primignani M, Randi ML, Santarossa C et al (2019) Splanchnic vein thromboses associated with myeloproliferative neoplasms: an international, retrospective study on 518 cases. Am J Hematol
Passamonti F, Malabarba L, Orlandi E, Baratè C, Canevari A, Brusamolino E, Bonfichi M, Arcaini L, Caberlon S, Pascutto C, Lazzarino M (2003) Polycythemia vera in young patients: a study on the long-term risk of thrombosis, MF and leukemia. Haematologica 88:13–18
Hoekstra J, Bresser EL, Smalberg JH, Spaander MC, Leebeek FW, Janssen HL (2011) Long-term follow-up of patients with portal vein thrombosis and myeloproliferative neoplasms. J Thromb Haemost 9:2208–2214
De Stefano V, Vannucchi AM, Ruggeri M, Cervantes F, Alvarez-Larrán A, Iurlo A et al (2016) Splanchnic vein thrombosis in myeloproliferative neoplasms: risk factors for recurrences in a cohort of 181 patients. Blood Cancer J 6:e493
Marchioli R, Finazzi G, Specchia G, Cacciola R, Cavazzina R, Cilloni D, de Stefano V, Elli E, Iurlo A, Latagliata R, Lunghi F, Lunghi M, Marfisi RM, Musto P, Masciulli A, Musolino C, Cascavilla N, Quarta G, Randi ML, Rapezzi D, Ruggeri M, Rumi E, Scortechini AR, Santini S, Scarano M, Siragusa S, Spadea A, Tieghi A, Angelucci E, Visani G, Vannucchi AM, Barbui T, CYTO-PV Collaborative Group (2013) Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med 368:22–33
Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, Randi ML, Bertozzi I, Gisslinger H, Buxhofer-Ausch V, De Stefano V, Betti S, Rambaldi A, Vannucchi AM, Tefferi A (2012) Development and validation of an international prognostic score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood 120:5128–5133
Ageno W, Riva N, Schulman S, Beyer-Westendorf J, Bang SM et al (2015) Long-term clinical outcomes of splanchnic vein thrombosis: results of an international registry. JAMA Intern Med 175:1474–1480
Barbui T, Ghirardi A, Masciulli A, Carobbio A, Palandri F, Vianelli N et al (2019) Second cancer in Philadelphia negative myeloproliferative neoplasms (MPN-K). A nested case-control study. Leukemia 33:1996–2005
Landtblom AR, Bower H, Andersson TM, Dickman PW, Samuelsson J, Björkholm M et al (2018) Second malignancies in patients with myeloproliferative neoplasms: a population-based cohort study of 9379 patients. Leukemia 32:2203–2210
Acknowledgments
We are indebted to investigators from GEMFIN and REHEVASC for their essential collaboration in data collection.
Funding
This work was supported by the grant PI18/00205 from the Instituto de Salud Carlos III (ISCIII), through the Plan Estatal de Investigación Científica y Técnica y de Innovación. JCGP received support in part by grants from Ministerio de Educación y Ciencia (SAF-2016-75767-R) from ISCCIII (PI17/00398) and from Comissionat per a Universitats i Recerca de la Generalitat de Catalunya (AGAUR SGR 2017). REHEVASC is funded by Asociación Española para el Estudio del Hígado (AEEH). CIBERehd is funded by the Instituto de Salud Carlos III. This work was co-funded by the European Regional Development Fund (ERDF).
Author information
Authors and Affiliations
Consortia
Contributions
AAL designed the study, collected the data, performed the statistical analysis, analyzed and interpreted the results, and wrote the paper. AP designed the study, performed the statistical analysis, analyzed and interpreted the results, and wrote the paper. MM collected the data, interpreted the results, and wrote the paper. JCHB and FC interpreted the results and wrote the paper. JGP designed the study, interpreted the results, and wrote the paper. MG, BC, FFM, MTGC, VGG, MIMV, FT, and VHG collected the data and approved the final version. A complete list of investigators participating in GEMFIN and REHEVASC studies is provided in supplementary appendix.
Corresponding author
Ethics declarations
Informed consent for the scientific use of the patients’ clinicohematological data was obtained, and the study was approved by the Hospital Clínic ethics’ committee.
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(DOCX 28 kb)
Rights and permissions
About this article
Cite this article
Alvarez-Larrán, A., Pereira, A., Magaz, M. et al. Natural history of polycythemia vera and essential thrombocythemia presenting with splanchnic vein thrombosis. Ann Hematol 99, 791–798 (2020). https://doi.org/10.1007/s00277-020-03965-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-020-03965-z