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Thromb Haemost
DOI: 10.1055/a-2605-9015
Stroke, Systemic or Venous Thromboembolism

Major Bleeding Risk Assessment in Patients with Cancer-Associated Venous Thromboembolism Treated with DOACs: Data from a Multicenter Cohort

Maria Cristina Vedovati 
1   Internal, Vascular and Emergency Medicine – Stroke Unit, University of Perugia, Perugia, Italy
,
Rosa Talerico 
2   Department of Geriatric, Orthopedic, and Rheumatologic Sciences, University Polyclinic Foundation A. Gemelli IRCCS, Rome, Italy
,
Clara Sacco
3   Thrombosis and Hemorragic Diseases Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
,
Matteo Mazzetti
4   Interdisciplinary Internal Medicine, Careggi University Hospital, Florence, Italy
,
Elena Campello 
5   First Chair of Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, University of Padova, Italy
,
Simone Birocchi
6   Medicine II Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy
,
Sofia Beccatini
1   Internal, Vascular and Emergency Medicine – Stroke Unit, University of Perugia, Perugia, Italy
,
Angelo Porfidia
2   Department of Geriatric, Orthopedic, and Rheumatologic Sciences, University Polyclinic Foundation A. Gemelli IRCCS, Rome, Italy
,
Rachele Caprari
2   Department of Geriatric, Orthopedic, and Rheumatologic Sciences, University Polyclinic Foundation A. Gemelli IRCCS, Rome, Italy
,
Corrado Lodigiani
3   Thrombosis and Hemorragic Diseases Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
,
Paolo Simioni
5   First Chair of Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, University of Padova, Italy
,
Gian Marco Podda
6   Medicine II Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy
,
Isabella Mastandrea
3   Thrombosis and Hemorragic Diseases Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
,
Cecilia Becattini
1   Internal, Vascular and Emergency Medicine – Stroke Unit, University of Perugia, Perugia, Italy
,
Roberto Pola 
2   Department of Geriatric, Orthopedic, and Rheumatologic Sciences, University Polyclinic Foundation A. Gemelli IRCCS, Rome, Italy
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Abstract

Background

In cancer-associated venous thromboembolism (CAT), extended anticoagulation should be considered when the risk–benefit profile is favorable. However, optimal predictors of major bleeding (MB) remain unclear.

Methods

This multicenter observational study included CAT patients treated with direct oral anticoagulants (DOACs). Study objectives were: (i) assess the performance of nine bleeding risk scores (ATRIA, CAT-BLEED, CHAP, DOAC, HAS-BLED, Kuijer, ORBIT, RIETE, VTE-BLEED), (ii) identify predictors of MB (ISTH definition), and (iii) propose an improved bleeding risk model (Perform score).

Results

Overall, 823 patients were followed (mean 1.6 years). MB occurred in 44 cases (3.4% per patient-year). The predictive performance of bleeding risk scores was modest (c-statistics range 0.513–0.606). Risk factors included increasing age (HR 1.04, 95% CI 1.00–1.07), use of steroids (HR 2.69, 95% CI 1.34–5.40), antimetabolites (HR 2.51, 95% CI 1.28–4.93), and unresected gastrointestinal cancer (HR 7.30, 95% CI 1.70–31.30). Conversely, prior cancer surgery (HR 0.41, 95% CI 0.20–0.82) and anticancer hormones (HR 0.22, 95% CI 0.05–0.92) showed a possible protective effect toward MB risk. The Perform score provided a slight enhancement in risk prediction (c-statistics 0.678), but remained suboptimal.

Conclusion

In this real-world cohort of CAT patients treated with DOACs, unresected gastrointestinal cancer and use of steroids or antimetabolites were associated with increased MB risk, while prior cancer surgery and anticancer hormones were linked to a lower risk. These factors, not considered in current bleeding risk scores, may refine bleeding prediction. Further studies should clarify their role in guiding anticoagulation decisions and improving personalized risk assessment.

Keywords

cancer - major bleeding - venous thromboembolism - prediction rule

Authors' Contribution

M.C.V., R.T., S.B., A.P., C.B. and R.P. contributed to study concept and design, major role in the acquisition of data, analysis or interpretation of data, drafting and revision of the manuscript critically for important intellectual content, and final approval of the version to be submitted. C.S., M.M., E.C., S.B., I.M., C.L., R.C., P.S. and G.M.P. contributed to major role in the acquisition of data, analysis or interpretation of data, drafting and revision of the manuscript critically for important intellectual content, and final approval of the version to be submitted.


Supplementary Material



Publication History

Received: 16 March 2025

Accepted: 12 May 2025

Article published online:
03 June 2025

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