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Cancer-associated venous thromboembolism

Nature Reviews Disease Primers volume 8, Article number: 11 (2022) Cite this article

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Abstract

Cancer-associated thrombosis (including venous thromboembolism (VTE) and arterial events) is highly consequential for patients with cancer and is associated with worsened survival. Despite substantial improvements in cancer treatment, the risk of VTE has increased in recent years; VTE rates additionally depend on the type of cancer (with pancreas, stomach and primary brain tumours having the highest risk) as well as on individual patient’s and cancer treatment factors. Multiple cancer-specific mechanisms of VTE have been identified and can be classified as mechanisms in which the tumour expresses proteins that alter host systems, such as levels of platelets and leukocytes, and in which the tumour expresses procoagulant proteins released into the circulation that directly activate the coagulation cascade or platelets, such as tissue factor and podoplanin, respectively. As signs and symptoms of VTE may be non-specific, diagnosis requires clinical assessment, evaluation of pre-test probability, and objective diagnostic testing with ultrasonography or CT. Risk assessment tools have been validated to identify patients at risk of VTE. Primary prevention of VTE (thromboprophylaxis) has long been recommended in the inpatient and post-surgical settings, and is now an option in the outpatient setting for individuals with high-risk cancer. Anticoagulant therapy is the cornerstone of therapy, with low molecular weight heparin or newer options such as direct oral anticoagulants. Personalized treatment incorporating risk of bleeding and patient preferences is essential, especially as a diagnosis of VTE is often considered by patients even more distressing than their cancer diagnosis, and can severely affect the quality of life. Future research should focus on current knowledge gaps including optimizing risk assessment tools, biomarker discovery, next-generation anticoagulant development and implementation science.

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Fig. 1: Consequences of cancer-associated VTE.
Fig. 2: VTE incidence over time in patients with and without cancer4.
Fig. 3: Survival in patients receiving immune checkpoint inhibitors11.
Fig. 4: Potential mechanisms of cancer-associated thrombosis.
Fig. 5: Clinical algorithm for management of cancer-associated VTE.
Fig. 6: Evolution of anticoagulant therapy.

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Acknowledgements

A.A.K. acknowledges research support from the Consortium Linking Oncology to Thrombosis (CLOT), funded by the National Heart, Lung and Blood Institute (U01 HL143402) and the Sondra and Stephen Hardis Endowed Chair in Oncology Research. A.A.K. also acknowledges D. Attia for editorial assistance. N.M. is supported by a grant from the National Heart, Lung and Blood Institute of the National Institutes of Health (R35 HL20011) and the John C. Parker Endowed Chair in Hematology. N.M. also acknowledges helpful comments from Y. Hisada. A.F. acknowledges support from the Italian Cancer Research Association (AIRC) and from ARTET Foundation. The authors thank the patients for sharing their experiences as outlined in Box 1.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Taussig Cancer Institute and Case Comprehensive Cancer Center, Cleveland Clinic, Cleveland, OH, USA

    Alok A. Khorana

  2. UNC Blood Research Center, Division of Hematology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Nigel Mackman

  3. Department of Medicine, University of Milan Bicocca, Milan, Italy

    Anna Falanga

  4. Department of Transfusion Medicine and Haematology, Hospital Papa Giovanni XXIII, Bergamo, Italy

    Anna Falanga

  5. Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria

    Ingrid Pabinger & Florian Moik

  6. Cardiff University, Cardiff, UK

    Simon Noble

  7. Università degli Studi dell’Insubria, Varese, Italy

    Walter Ageno

  8. Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

    Florian Moik

  9. University of British Columbia, Vancouver, BC, Canada

    Agnes Y. Y. Lee

  10. BC Cancer, Vancouver, BC, Canada

    Agnes Y. Y. Lee

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  1. Alok A. Khorana
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Contributions

Introduction (A.A.K., N.M., A.F., S.N., W.A. and A.Y.Y.L.); Epidemiology (A.A.K., I.P., F.M. and A.Y.Y.L.); Mechanisms/pathophysiology (N.M., A.F. and I.P.); Diagnosis, screening and prevention (A.A.K. and W.A.); Management (A.A.K., N.M., A.F. and A.Y.Y.L.); Quality of life (S.N. and A.Y.Y.L.); Outlook (A.A.K., I.P., S.N. and A.Y.Y.L.); Overview of primer (A.A.K.).

Corresponding author

Correspondence to Alok A. Khorana.

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Competing interests

A.A.K. received honoraria from Janssen, Bayer, BMS, Pfizer, Sanofi, Anthos and Halozyme. N.M. received a research grant from GSK. W.A. received honoraria from Bayer, Portola, Sanofi, Aspen, Norgine, Leo Pharma and BMS-Pfizer, and research support from Bayer. S.N. received honoraria for delivering lectures from Leo Pharma, BMS-Pfizer Alliance, and grant support from Leo Pharma. A.F. was a speaker at corporate symposia (Bayer, Sanofi, Pfizer, Leo Pharma), and participated on advisory boards (Bayer, Sanofi). A.Y.Y.L. received honoraria from Bayer, BMS-Pfizer, Leo Pharma, Pfizer and Servier, and research support from BMS. I.P. received honoraria from Bayer, BMS, Pfizer, Sanofi and Daiichi Sanchyo. F.M. declares no competing interests.

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Nature Reviews Disease Primers thanks S. Cannegieter, J. Hansen, P. M. Sandset, H. T. Sorensen and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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The Human Protein Atlas: http://www.proteinatlas.org/

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Khorana, A.A., Mackman, N., Falanga, A. et al. Cancer-associated venous thromboembolism. Nat Rev Dis Primers 8, 11 (2022). https://doi.org/10.1038/s41572-022-00336-y

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