Thromb Haemost 2022; 122(05): 818-829
DOI: 10.1055/s-0041-1735251
Stroke, Systemic or Venous Thromboembolism

Estimating Bleeding Risk in Patients with Cancer-Associated Thrombosis: Evaluation of Existing Risk Scores and Development of a New Risk Score

Maria A. de Winter
1   Department of Acute Internal Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
Jannick A. N. Dorresteijn
2   Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
Walter Ageno
3   Department of Medicine and Surgery, University of Insubria, Varese, Italy
Cihan Ay
4   Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
5   I. M. Sechenov First Moscow State Medical University, Moscow, Russia
Jan Beyer-Westendorf
6   Department of Hematology/Hemostasis, Dresden University Hospital “Carl-Gustav Carus,” Dresden, Germany
Michiel Coppens
7   Department of Vascular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands
8   Department of Medicine—Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
Farès Moustafa
9   Department of Emergency, Clermont-Ferrand University Hospital, Clermont-Ferrand, France
10   Department of Pathology, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
11   Department of Internal Medicine, Clínica Universidad de Navarra, Madrid, Spain
12   CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain
13   Interdisciplinar Teragnosis and Radiosomics Research Group (INTRA-Madrid), Universidad de Navarra, Madrid, Spain
Thomas Vanassche
14   Department of Cardiology, Leuven University Hospital, Leuven, Belgium
Mathilde Nijkeuter
1   Department of Acute Internal Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
› Author Affiliations
Funding All authors except M.A.d.W. and J.A.N.D. are member of TEAM (Thrombosis ExchAnge Program). TEAM has received network sponsoring from Daiichi Sankyo, Inc. No other funding has been received for this project.


Background Bleeding risk is highly relevant for treatment decisions in cancer-associated thrombosis (CAT). Several risk scores exist, but have never been validated in patients with CAT and are not recommended for practice.

Objectives To compare methods of estimating clinically relevant (major and clinically relevant nonmajor) bleeding risk in patients with CAT: (1) existing risk scores for bleeding in venous thromboembolism, (2) pragmatic classification based on cancer type, and (3) new prediction model.

Methods In a posthoc analysis of the Hokusai VTE Cancer study, a randomized trial comparing edoxaban with dalteparin for treatment of CAT, seven bleeding risk scores were externally validated (ACCP-VTE, HAS-BLED, Hokusai, Kuijer, Martinez, RIETE, and VTE-BLEED). The predictive performance of these scores was compared with a pragmatic classification based on cancer type (gastrointestinal; genitourinary; other) and a newly derived competing risk-adjusted prediction model based on clinical predictors for clinically relevant bleeding within 6 months after CAT diagnosis with nonbleeding-related mortality as the competing event (“CAT-BLEED”).

Results Data of 1,046 patients (149 events) were analyzed. Predictive performance of existing risk scores was poor to moderate (C-statistics: 0.50–0.57; poor calibration). Internal validation of the pragmatic classification and “CAT-BLEED” showed moderate performance (respective C-statistics: 0.61; 95% confidence interval [CI]: 0.56–0.66, and 0.63; 95% CI 0.58–0.68; good calibration).

Conclusion Existing risk scores for bleeding perform poorly after CAT. Pragmatic classification based on cancer type provides marginally better estimates of clinically relevant bleeding risk. Further improvement may be achieved with “CAT-BLEED,” but this requires external validation in practice-based settings and with other DOACs and its clinical usefulness is yet to be demonstrated.

Author Contributions

All authors contributed to study conception and design. M.A. de Winter analyzed the data and drafted the manuscript in close collaboration with J.A.N. Dorresteijn and M. Nijkeuter. All authors critically revised the manuscript, were responsible for and approved its final version.

Supplementary Material

Publication History

Received: 08 April 2021

Accepted: 23 July 2021

Article published online:
20 September 2021

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