CC BY-NC-ND 4.0 · Thromb Haemost 2024; 124(07): 669-675
DOI: 10.1055/a-2239-9265
New Technologies, Diagnostic Tools and Drugs

DNMT3A/TET2/ASXL1 Mutations are an Age-independent Thrombotic Risk Factor in Polycythemia Vera Patients: An Observational Study

Adrián Segura-Díaz*
1   Hematology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
Ruth Stuckey*
1   Hematology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
Yanira Florido
1   Hematology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
Marta Sobas
2   Department of Hematology and Bone Marrow Transplantation, Wrocław Medical University, Wrocław, Poland
Alberto Álvarez-Larrán
3   Hematology Department, Hospital Clínic, Barcelona, Spain
Francisca Ferrer-Marín
4   Hematology Department, Hospital Morales Messeguer, Instituto Murciano de Investigación Biosanitaria, Centro de Investigación Biomédica en Red de Enfermedades Raras, Universidad Católica San Antonio de Murcia, Murcia, Spain
Manuel Pérez-Encinas
5   Hematology Department, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
Gonzalo Carreño-Tarragona
6   Hematology Department, Hospital Universitario 12 de Octubre, Madrid, Spain
María L. Fox
7   Hematology Department, Hospital Vall d'Hebron, Barcelona, Spain
Barbara Tazón Vega
7   Hematology Department, Hospital Vall d'Hebron, Barcelona, Spain
Beatriz Cuevas
8   Hematology Department, Hospital Universitario de Burgos, Burgos, Spain
Juan F. López Rodríguez
1   Hematology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
Nuria Sánchez-Farías
1   Hematology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
Jesús M. González-Martín
9   Investigation Unit, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain
María T. Gómez-Casares
1   Hematology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
10   Department of Medical Sciences, Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain
Cristina Bilbao-Sieyro
1   Hematology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
11   Morphology Department, Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain
on behalf of the Spanish MPN Group (GEMFIN) › Author Affiliations
Funding This study was supported by funding from the Fundación DISA.


Background Polycythemia vera (PV) patients are classified as high or low thrombotic risk based on age and prior history of thrombosis. Despite adherence to treatment recommendations, vascular events remain frequent, leading us to question whether thrombotic risk stratification could be improved. We previously reported an association between thrombotic events and mutations in DTA genes (DNMT3A, TET2, and ASXL1). The objective of this study was to confirm this observation in a larger series of PV patients.

Methods PV patients with a minimum follow-up of 3 years were recruited from 8 European centers. Medical history was searched for thrombotic event recorded at any time and next-generation sequencing carried out with a myeloid panel. Multivariable logistic regression evaluated the impact of variables on thrombotic risk. Kaplan–Meier thrombosis-free survival curves were compared by the log rank test. Associations in the total cohort were confirmed in a case–control study to exclude selection bias.

Results Of the 136 patients recruited, 74 (56.1%) had a thrombotic event, with an incidence density of 2.83/100 person-years. In multivariable analysis, DTA mutation was a risk factor for thrombotic event, being predictive for shorter thrombosis-free survival in the whole cohort (p = 0.007), as well as in low-risk patients (p = 0.039) and older patients (p = 0.009), but not for patients with a prediagnostic event. A gender- and age-matched case–control study confirmed the increased risk of thrombotic event for PV patients with a DTA mutation.

Conclusion Our results support the use of molecular testing at diagnosis to help predict which PV patients are at higher risk of developing thrombosis.

Ethical Approval Statement

This retrospective noninterventional study was approved by our Institutional Review Board (Comité Ético de Investigación Clínica, ref. 2019-230-1) on March 28, 2019 and conducted in accordance with the Declaration of Helsinki. All patient data were dissociated and anonymized; informed consent was not required due to the retrospective nature of the study and because the results did not affect the clinical management of patients.

Data Availability Statement

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Authors' Contribution

A.S.D. contributed data, curated data, analyzed the data, and wrote the paper; R.S. coordinated the study, curated data, analyzed the data, performed statistical analysis, and wrote the paper; Y.F. performed next-generation sequencing; M.S., A.A.L., F.F.M., M.P.E., G.C.T., M.L.F., B.T.V., and B.C. contributed data, J.F.L.R. and N.F.S. curated data; J.M.G.M. performed statistical analysis; M.T.G.C. designed the research study; C.B.S. designed the research study, performed statistical analysis and wrote the paper. All authors read and approved the final version of the manuscript.

* These authors contributed equally to this work.

Supplementary Material

Publication History

Received: 11 September 2023

Accepted: 23 December 2023

Accepted Manuscript online:
08 January 2024

Article published online:
30 January 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (

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