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. 2024 Dec 10;8(23):6043-6054.
doi: 10.1182/bloodadvances.2024013777.

Risk of bleeding in patients with essential thrombocythemia and extreme thrombocytosis

Rathnam K Venkat  1 , Robert A Redd  2 , Amyah C Harris  3 , Martin J Aryee  2   4 , Anna E Marneth  5   6 , Baransel Kamaz  6 , Chulwoo J Kim  6 , Mohammed Wazir  7 , Lachelle D Weeks  3 , Maximilian Stahl  3 , Daniel J DeAngelo  3 , R Coleman Lindsley  3 , Marlise R Luskin  3 , Gabriela S Hobbs  8 , Joan How  3   6
Affiliations

Risk of bleeding in patients with essential thrombocythemia and extreme thrombocytosis

Rathnam K Venkat et al. Blood Adv. .

Abstract

Approximately 25% of patients with essential thrombocythemia (ET) present with extreme thrombocytosis (ExT), defined as having a platelet count ≥1000 × 109/L. ExT patients may have an increased bleeding risk associated with acquired von Willebrand syndrome. We retrospectively analyzed the risk of bleeding and thrombosis in ExT vs non-ExT patients with ET at Dana-Farber Cancer Institute and Massachusetts General Hospital from 2014 to 2022 to inform treatment decisions. We abstracted the first major bleed, clinically relevant nonmajor bleed (CRNMB), and thrombotic events from medical records. We identified 128 ExT patients (28%) and 323 non-ExT patients (72%). Cumulative incidence of bleeding was not different in ExT vs non-ExT patients (21% vs 13% [P = .28] for major bleed; 16% vs 15% [P = .50] for CRNMB). Very low and low thrombotic risk ExT patients were more likely to be cytoreduced than very low- and low-risk non-ExT patients (69% vs 50% [P = .060] for very low risk; 83% vs 53% [P = .0059] for low risk). However, we found no differences in bleeding between ExT and non-ExT patients when restricting the risk of bleed from diagnosis to cytoreduction start date (28% vs 19% [P = .29] for major bleed; 24% vs 22% [P = .75] for CRNMB). Cumulative incidence of thrombosis was also not different between ExT and non-ExT patients (28% vs 25%; P = .98). This suggests that cytoreduction may not be necessary to reduce bleeding risk based only on a platelet count of 1 million. We identified novel risk factors for bleeding in patients with ET including diabetes mellitus and the DNMT3A mutation.

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Conflict of interest statement

Conflict-of-interest disclosure: M.J.A. reports consultancy fees from and being a current equity holder in private company, SeQure Dx. L.D.W. reports consultancy fees from AbbVie and Vertex, and membership on an entity's board of directors or advisory committee for Sobi. M.S. reports membership on an entity's board of directors or advisory committees for Rigel, Novartis, Sierra Oncology, Kymera, and GlaxoSmithKline; other interests including graduate medical education activity in Haymarket Media, Clinical Care Options, Novartis, and Curis Oncology; and consultancy fees from Dedham group and Boston Consulting. D.J.D. reports honoraria from Pfizer, Incyte, Amgen, Takeda, Servier, Jazz, Kite, Blueprint, Autolus, Novartis, and Gilead, and research funding from AbbVie, Novartis, Blueprint, and GlycoMimetics. R.C.L. reports consultancy fees from Takeda Pharmaceuticals, bluebird bio, Qiagen, Sarepta Therapeutics, Verve Therapeutics, Jazz Pharmaceuticals, and Vertex Pharmaceuticals, and membership on an entity's board of directors or advisory committee for bluebird bio. M.R.L. reports research funding from AbbVie and Novartis, and honoraria from Jazz, Pfizer and Novartis. G.S.H. reports research funding from Incyte and MorphoSys; membership on an entity's board of directors or advisory committees for Keros, Pharmaxis, Pfizer, MorphoSys, Novartis, Protagonist, AbbVie, and Bristol Myers Squibb; and is current holder of stock options in a privately held company, Regeneron. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Cumulative incidence of major bleeding and CRNMB in ExT and non-ExT patients with death as a competing event. (A) Full follow-up. (B) Follow-up restricted to the start date of cytoreduction. Plt, platelet.
Figure 2.
Figure 2.
Two-year cumulative incidence of major bleeding and CRNMB in ExT and non-ExT patients with death as a competing event. (A) Full follow-up. (B) Follow-up restricted to the start date of cytoreduction. Plt, platelet.
Figure 3.
Figure 3.
Multivariable model assessing the association of factors associated with major and clinically relevant non-major bleeding in ET patients.
Figure 4.
Figure 4.
Kaplan-Meier analysis illustrating overall survival, myelofibrosis-free survival, leukemia-free survival, thrombosis-free survival, and bleeding-free survival in ExT and non-ExT patients. (A) Overall survival. (B) Myelofibrosis-free survival. (C) Leukemia-free survival. (D) Thrombosis-free survival. (E) Bleeding-free survival.
See this image and copyright information in PMC

References

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