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Observational Study
. 2025 Dec;23(12):3932-3939.
doi: 10.1016/j.jtha.2025.08.022. Epub 2025 Sep 5.

Management of recurrent venous thromboembolism during anticoagulant treatment in patients with cancer: a prospective cohort study

Vincent R Lanting  1 , Floris T M Bosch  2 , Emily S L Martens  3 , Pieter W Kamphuisen  2 , Stefano Barco  4 , Ramón Lecumberri  5 , Hans-Martin Otten  6 , Francesca Schieppati  7 , Corrado Lodigiani  8 , María Barca-Hernando  9 , Elena Campello  10 , Frederikus A Klok  3 , Luis Jara-Palomares  9 , Ettore Porreca  11 , Harry R Büller  12 , Nick van Es  12 , Marcello Di Nisio  13
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Free article
Observational Study

Management of recurrent venous thromboembolism during anticoagulant treatment in patients with cancer: a prospective cohort study

Vincent R Lanting et al. J Thromb Haemost. 2025 Dec.
Free article

Abstract

Background: Recurrent venous thromboembolism (VTE) is a common complication in patients with cancer-associated VTE. Limited data are available on treatment, particularly in patients receiving direct oral anticoagulants (DOACs).

Objectives: We aimed to evaluate current management strategies and outcomes in patients with cancer and recurrent VTE during treatment with low-molecular-weight heparin (LMWH) or DOACs.

Methods: This was an international, prospective, observational cohort study. Patients were treated according to local practice, although the study protocol encouraged the use of a dose-escalation strategy in accordance with current clinical guidelines. Primary outcomes were second recurrent VTE and clinically relevant bleeding.

Results: Between June 2020 and November 2024, 94 patients were enrolled, of whom 81 were included in the final analysis. At the time of recurrent VTE, 55% of patients were treated with a DOAC, 41% with therapeutic-dose LMWH, and 4% with maintenance-dose LMWH. Of DOAC-treated patients, 51% switched to supratherapeutic-dose LMWH, 42% to therapeutic-dose LMWH, and 7% received other treatments. Of LMWH-treated patients, 70% received dose escalation, 18% maintained the same dose, and 12% received other treatments. At the 3-month follow-up, 10% had developed a second recurrence, 12% clinically relevant bleeding, and 20% died. VTE incidence was similar between patients receiving dose escalation and those maintained on therapeutic doses, while clinically relevant bleeding was more frequent in the latter (6% vs 25%).

Conclusion: The risk of second recurrent VTE was substantial despite two-thirds of patients receiving dose escalation. Bleeding was common regardless of treatment intensity, underscoring the challenges in this patient population.

Keywords: anticoagulants; direct oral anticoagulants; low-molecular-weight heparin; neoplasms; venous thromboembolism.

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Conflict of interest statement

Declaration of competing interests P.W.K. reports research funding from Daiichi-Sankyo and Roche diagnostics. H.R.B. reports research support from Sanofi-Aventis, Bayer HealthCare, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Pfizer, Roche, IONIS, Boehringer Ingelheim, Eli Lilly, and Novartis; consultancy fees from Sanofi-Aventis, Bayer HealthCare, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Pfizer, Roche, IONIS, Boehringer Ingelheim, Eli Lilly, and Novartis; and participation in scientific advisory board of Sanofi-Aventis, Bayer HealthCare, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Pfizer, Roche, IONIS, Boehringer Ingelheim, Eli Lilly, and Novartis. N.v.E. reports advisory board honoraria from Daiichi-Sankyo, LEO Pharma, and Bayer, which were transferred to his institute. M.D.N. has served as a consultant and has received honoraria from Daiichi-Sankyo, Janssen, Leo Pharma, and Mylan. F.A.K. received research funding from Bayer, BMS, BSCI, AstraZeneca, MSD, Leo Pharma, angiodynamics, Actelion, Farm-X, The Netherlands Organisation for Health Research and Development, The Dutch Heart Foundation, and the Horizon Europe Program, all outside this work and paid to his institution. The other authors have no competing interests.

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