Predictors of recurrent venous thromboembolism and bleeding in patients with cancer: a meta-analysis

Faizan Khan; Tobias Tritschler; Caterina E Marx; Vincent Lanting; Bram Rochwerg; Alexandre Tran; Shannon M Fernando; Diane L Lorenzetti; Hannah Wunsch; Jessalyn Holodinsky; Kirsten Fiest; Henry Thomas Stelfox; Aurélien Delluc; Dean A Fergusson; Grégoire Le Gal; Philip S Wells; Tzu-Fei Wang; Kristen Sanfilippo; Nick van Es; Deborah Schrag; Jean M Connors; Marc Carrier

doi:10.1093/eurheartj/ehaf453

Predictors of recurrent venous thromboembolism and bleeding in patients with cancer: a meta-analysis

Eur Heart J. 2026 Apr 22;47(16):1917-1929. doi: 10.1093/eurheartj/ehaf453.

Authors

Faizan Khan¹, Tobias Tritschler^{2

3}, Caterina E Marx², Vincent Lanting^{4

5}, Bram Rochwerg⁶, Alexandre Tran^{3

7}, Shannon M Fernando^{8

9}, Diane L Lorenzetti¹⁰, Hannah Wunsch¹¹, Jessalyn Holodinsky¹², Kirsten Fiest¹³, Henry Thomas Stelfox¹⁴, Aurélien Delluc^{3

15}, Dean A Fergusson³, Grégoire Le Gal^{3

15}, Philip S Wells^{3

15}, Tzu-Fei Wang^{3

15}, Kristen Sanfilippo¹⁶, Nick van Es⁴, Deborah Schrag¹⁷, Jean M Connors¹⁸, Marc Carrier^{3

15}

Affiliations

¹ Department of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, 3330 Hospital 83 Drive NW, Calgary, Alberta, Canada T2N 4N1.
² Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
³ Inflammation and Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
⁴ Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
⁵ Department of Internal Medicine, Tergooi Hospital, Hilversum, The Netherlands.
⁶ Departments of Medicine and Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.
⁷ Departments of Medicine and Surgery, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
⁸ Department of Critical Care, Lakeridge Health, Oshawa, Ontario, Canada.
⁹ Department of Critical Care Medicine, Queen's University, Kingston, Ontario, Canada.
¹⁰ Department of Community Health Sciences, Cumming School of Medicine and Health Sciences Library, University of Calgary, Calgary, Alberta, Canada.
¹¹ Department of Anesthesiology, Weill Cornell Medical College, New York, NY, USA.
¹² Departments of Emergency Medicine, Community Health Sciences, and Clinical Neurosciences, Centre for Health Informatics, O'Brien Institute for Public Health, Hotchkiss Brain Institute, Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
¹³ Departments of Critical Care Medicine and Community Health Sciences, O'Brien Institute for Public Health, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
¹⁴ Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
¹⁵ Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
¹⁶ Department of Medicine, St. Louis Veterans Administration Medical Center, Washington University School of Medicine, St. Louis, MO, USA.
¹⁷ Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁸ Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

PMID: 40579365
PMCID: PMC13099206 (available on 2026-06-22)
DOI: 10.1093/eurheartj/ehaf453

Abstract

Background and aims: Patients with cancer and venous thromboembolism (VTE) have a high risk of recurrent VTE and anticoagulant-related bleeding. This study aimed to identify prognostic factors for these complications.

Methods: A systematic review was performed for randomized trials and cohort studies evaluating prognostic factors for recurrent VTE or anticoagulant-related bleeding in adult patients with cancer and VTE. Adjusted hazard ratios (aHRs) for factors were pooled using random-effects meta-analysis. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach.

Results: Thirty-three studies (n = 96 753) were included in the meta-analyses. Factors with high certainty of association with increased risk of recurrent VTE included a previous history of VTE [aHR 1.50 (95% CI 1.08-2.09)], Eastern Cooperative Oncology Group (ECOG) performance status >0 [1.81 (1.34-2.46)] or >1 [2.44 (1.55-3.84)], advanced cancer [1.38 (1.15-1.65)], and specific cancer sites including lung [1.78 (1.29-2.46)], hepatobiliary [2.37 (1.70-3.30)], pancreas [3.20 (2.06-4.96)], and genitourinary [1.38 (1.14-1.67)]. Conversely, recent surgery [aHR 0.56 (95% CI 0.40-0.76)] and breast cancer [0.43 (0.23-0.81)] had a high certainty of association with a decreased risk. Factors with a high certainty of association with an increased risk of anticoagulant-related bleeding included a history of bleeding [aHR 2.41 (95% CI 1.50-3.88)], ECOG performance status ≥2 [2.10 (1.48-2.99)], advanced cancer [1.60 (1.29-1.97)], and cancers of the brain [2.25 (1.64-3.09)], gastrointestinal system [1.74 (1.44-2.11)], genitourinary system [1.90 (1.48-2.45)], and prostate [1.72 (1.26-2.34)].

Conclusions: The prognostic factors identified in this meta-analysis should be considered as part of risk stratification frameworks for anticoagulation management in patients with cancer and VTE.

Keywords: Bleeding; Cancer; Venous thromboembolism.

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Publication types

Meta-Analysis
Systematic Review
Review

MeSH terms

Adult
Anticoagulants* / adverse effects
Female
Hemorrhage* / chemically induced
Humans
Male
Neoplasms* / complications
Prognosis
Randomized Controlled Trials as Topic
Recurrence
Risk Factors
Venous Thromboembolism* / etiology

Substances

Anticoagulants

Abstract

Publication types

MeSH terms

Substances

Grants and funding