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Review
. 2025 Jul;104(7):3553-3566.
doi: 10.1007/s00277-025-06466-z. Epub 2025 Jul 18.

Exploring thromboembolic risk factors in polycythemia vera: from current evidence to PROSPERO study design

Valerio De Stefano #  1   2 , Francesco Passamonti #  3   4 , Francesca Palandri  5 , Francesco Ramundo  2 , Elena Rossi  1   2 , Silvia Betti  2 , Lorenzo Fagiolo  6 , Paola Guglielmelli  6 , Davide Pio Abagnale  7 , Novella Pugliese  7 , Daniele Cattaneo  4   8 , Alessandra Iurlo  8 , Filippo Branzanti  9 , Alessandra Dedola  9 , Hillary Catellani  10 , Alessia Tieghi  10 , Marco Basso  11 , Elisabetta Calistri  11 , Elena Maria Elli  12 , Elena Masselli  13 , Erika Morsia  14 , Giulia Benevolo  15 , Massimo Breccia  16 , Vincenza de Fazio  17 , Maria Di Perna  18 , Monia Marchetti  19 , Marco Santoro  20 , Agostino Tafuri  21 , Chiara Castiglioni  22 , Chiara Rotella  22 , Sergio Siragusa #  20 , Alessandro Maria Vannucchi #  6 ; PROSPERO Study group
Affiliations
Review

Exploring thromboembolic risk factors in polycythemia vera: from current evidence to PROSPERO study design

Valerio De Stefano et al. Ann Hematol. 2025 Jul.

Abstract

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm with a substantial risk of thromboembolic events (TEs), which contribute to morbidity and mortality. Traditional thrombotic risk stratification primarily considers age and thrombosis history, yet these parameters alone do not capture the complexity of thrombotic risk. Growing evidence highlights the role of additional factors influencing the risk of TEs, underscoring the need for a more comprehensive approach to patient stratification. This paper reviews the current understanding of thromboembolic risk factors in PV and provides the rationale, methodology, and expected contributions of the PROSPERO study, a prospective, multicenter study designed to improve thrombotic risk assessment in patients with high-risk PV. By examining established (advanced age, prior TEs, cardiovascular comorbidities) and emerging thromboembolic risk factors, including specific hematologic parameters, the study aims to emphasize their impact and potential synergistic interactions on thrombotic risk. This review also evaluates the efficacy and limitations of current therapies, such as hydroxyurea (HU), interferons, and ruxolitinib, in preventing TEs, and further underscores the need for comprehensive predictive models to guide individualized management strategies. The PROSPERO study focuses on high-risk PV patients who experienced at least one prior TE and receive either HU or ruxolitinib, aiming to identify predictive factors for TEs and their individual and combined contributions to thrombotic risk by collecting longitudinal data on clinical, laboratory, and treatment-related parameters. PROSPERO aims to identify and validate new variables that can inform the development of precise, integrated prediction models. The findings are expected to enable tailored treatment approaches, ultimately reducing TE recurrence in high-risk PV populations.

Keywords: Hydroxyurea; PROSPERO study; Polycythemia Vera; Risk factors; Risk stratification; Ruxolitinib; Thromboembolic risk.

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Conflict of interest statement

Declarations. Human and animal rights: This work does not contain any studies on human or animal subjects performed by any of the authors. Ethics approval: Not applicable to this work. The PROSPERO study protocol was submitted to and approved by the Ethics Committee of each participating center. Competing interests: CC and CR are Novartis employees. VDS: advisory board for AOP Health, Bristol Myers Squibb, Glaxo Smith Kline, Grifols, Novartis, SOBI, Takeda; speaker fees from Abbvie, Alexion, Amgen, Bristol Myers Squibb, Grifols, Novartis, Novo Nordisk, Sanofi, Takeda; research grant from Alexion. GB: Advisory board for Novartis, GSK; speakers bureau of Novartis, BMS, Janssen, Menarini, GSK. MB: honoraria by Novartis, Incyte, Pfizer, BMS, AOP, Abbvie, GSK. AI: speaker honoraria from AOP Health and Novartis. MM: consultant for AstraZeneca, Roche, Novartis, Gilead, MSD. E. Masselli: consultancy and honoraria from Novartis, BMS and GSK. F. Palandri: speakers bureau and advisory board of Novartis, BMS, AOP, Sierra Oncology, Incyte, Telios, Abbvie, Constellation-Morphosys, Sobi and GSK. F. Passamonti: honoraria during the last two years for lectures from Novartis, Bristol-Myers Squibb, Abbvie, GSK, AOP Orphan, Jazz and for advisory boards from Novartis, Bristol-Myers Squibb/Celgene, GSK, Abbvie, Keros, Sumitomo. NP: advisory board for Novartis, GSK; consultant for AOP. The other authors have nothing to declare. F. Palandri and M. Breccia serve as editors for the Annals of Hematology journal.

Figures

Fig. 1
Fig. 1
Schematic illustration of the PROSPERO study design. ELN, European Leukemia Net; HU, Hydroxyurea; PV, Polycythemia vera; RUXO, Ruxolitinib; TE, thromboembolic event
See this image and copyright information in PMC

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