Impact of anticoagulant choice on hospitalized bleeding risk when treating cancer-associated venous thromboembolism

N. A. Zakai, R. F. Walker, Richard F Maclehose, Terrence J Adam, A. Alonso, Pamela L Lutsey

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Essentials Bleeding risk by anticoagulant choice for cancer-associated venous thrombosis (CA-VTE) is unknown. 26 894 people with CA-VTE were followed for bleeding in a claims database in the United States. Hospitalized bleeding risk was similar with direct acting oral anticoagulants vs. warfarin. Relative hospitalized bleeding risk varied by cancer type and anticoagulant choice. Summary: Background Direct acting oral anticoagulants (DOACs) are associated with less bleeding than traditional venous thromboembolism (VTE) treatments in the general population but are little studied in cancer-associated VTE (CA-VTE). Objective To determine whether different anticoagulation strategies for CA-VTE have different hospitalized bleeding rates. Patients/Methods We conducted a retrospective study of patients with CA-VTE, diagnosed between 2011 and 2015, in a large administrative database. Using validated algorithms, we identified 26 894 CA-VTE patients treated with anticoagulants and followed them for hospitalized severe bleeding. Cox models were used to assess bleeding risk, adjusted for age, sex, high dimensional propensity score and frailty. Results Over 27 281 person-years of follow-up (median 0.6 years), 1204 bleeding events occurred, for a bleeding rate of 4.4% per patient-year. Bleeding rates varied by cancer type, with the highest rate for upper gastrointestinal cancers (8.6%) and the lowest for breast cancer (2.9%). In Cox models (hazard ratio [HR]; 95% confidence interval [CI]), compared with warfarin, DOACS and low-molecular-weight heparin (LMWH) had similar hazards of bleeding (HR, 0.88; 95% CI, 0.69–1.11 and 0.98; 0.85–1.13). Compared with LMWH, there was no difference in hazard of bleeding with DOACs (0.86; 0.66–1.12). There was heterogeneity in bleeding risk with DOACs by cancer type, with a higher risk of bleeding in upper gastrointestinal cancers and lower risk of bleeding in prostate cancer and hematologic cancers. Conclusions In this practice-based sample of CA-VTE patients, DOACs were associated with similar bleeding risks to warfarin and LMWH. These findings suggest a complex association of bleeding risk with anticoagulant choice in cancer patients.

Original languageEnglish (US)
Pages (from-to)2403-2412
Number of pages10
JournalJournal of Thrombosis and Haemostasis
Issue number12
StatePublished - Dec 2018

Bibliographical note

Publisher Copyright:
© 2018 International Society on Thrombosis and Haemostasis


  • anticoagulants
  • drug utilization
  • hemorrhage
  • neoplasms
  • venous thrombosis


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